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Scientific Program EPNS BRUSSELS 2013 Wednesday 25 September 2013 07:30 -­‐ 08:15 Early Rise Sessions 1-­‐3 ERS 1: Microcephaly: Clinical and Molecular Work-­‐up Marc Abramowicz -­‐ Anna Jansen ERS2: MRI of fetal and infant brain development Alec Aeby -­‐ Marie Cassart ERS3: Macrocephaly clinical and molecular work-­‐up Marie Cecile Nassogne -­‐ Yves Sznajer 8.30 -­‐ 08:40 Opening of the Congress: Linda De Meirleir and Lieven Lagae Gold Room 08:40 -­‐ 10:00 Plenary Session 1: Fetal Neurology Gold Room Chairs: Inge Krageloh-­‐Mann and Patrick Van Bogaert IL 1 MRI of the fetal Brain -­‐ Elspeth Witby IL 2 Fossa Posterior abnormalities in the fetus -­‐ Tally Lerman -­‐ Sagie IL 3 Outcome of lesions in the fetus -­‐ Thierry Billette de Villemeur 10:00 -­‐ 10:30 Coffee break and poster viewing 10:30 -­‐ 12:15 Parallel Sessions 1-­‐3 Parallel session 1 Movement Disorders Chairs: Michèl Willemsen and Emilio Alvarez Fernandez IL 4 Michèl Willemsen IL 5 Emilio Alvarez Fernandez O1 -­‐ 1990 Clinical Spectrum of Dopamine Transporter Deficiency Syndrome: from infantile parkinsonism-­‐dystonia to juvenile parkinsonism Ng J, Li Y, Zhen J, Kakar N, Ahmad J, Thiele H, Kubisch C, Rider N, Strauss K, Holmes-­‐Morton D, D’Agnano D Anikster Y, Carducci C, Hyland K, Rostein M, Leuzzi V, Borck G, Reith MEA, Kurian MA. Neurosciences, Institute Child Health-­‐UCL, UK -­‐ [email protected] O2 -­‐ 2122 Dystonia in previously well children-­‐ two years experience in a UK tertiary centre Pathak D, Whitney A, Forrest K, Kirkham F. University Hospitals Southampton -­‐ [email protected] O3 -­‐ 2102 GLUT1 deficiency syndrome from infancy into adulthood: a follow-­‐up study Leen WG, Taher M, Mewasingh L, Willemsen Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands -­‐ [email protected] 1 O4 -­‐2020 Electroneuromyography parameters in hereditary and congenital ataxia Milic Rasic V, Brankovic V, Mladenovic J , Kosac A, Todorovic S. Clinic for neurology and psychiatry for children and youth, Medical Faculty, University of Belgrade, Belgrade, Serbia -­‐ [email protected] Parallel session 2: Epileptic encephalopathies Chairs: Raili Riikonen and Alec Aeby O5 -­‐ 1819 Impaired slow wave sleep downscaling in infantile spasms with hypsarrhythmia Fattinger S, Schmitt B, Bölsterli B, Critelli H, Jenni O, Huber R. University Children’s Hospital Zurich, Switserland -­‐ [email protected] O6 -­‐ 2105 KCNT1 mutations in a national cohort of children with migrating partial seizures of infancy McTague A, Meyer E, Appleton RE, Lascelles K, Desurkar A, Kneen R, Kurian MA. Neurosciences unit UCL, London, UK -­‐ [email protected] O7 -­‐ 2139 Epilepsy and PCDH19 mutation: electrophysiological features Chemaly N, Kaminska A, Chiron C, An I, Pinard JM, Gauthier A, Arbues AS, Dulac O, Nabbout R. Neuropediatrics department, Centre de référence des épilepsies rares, Necker Enfants Malades Hospital, Paris, France -­‐ [email protected] O8 -­‐ 2053 Epileptic spasms beyond infancy. Is LOES more than a description? Schoonjans A, Kenis S, Verhaert K, Van de Vel A, Ceulemans B. Antwerp University Hospital, Belgium -­‐ an-­‐[email protected] O9 -­‐ 2019 Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2 Milh M, Boutry-­‐Kryza N, Sutera-­‐Sardo J, Mignot C, Auvin S, Villenueve N, Roubertie A, Héron B, Kaminska A, Altuzara, Blanchard G, Ville D, Barthez H, Héron D, Afenjar A, Dorison N, Billette de Vileumeure T, Vercueil L, Perrier J, Lesca G, Villard L. Marseille, France -­‐ [email protected]­‐hm.fr O10 -­‐ 1986 Effective use of low dose of rufinamide after an initial worsening effect in Lennox-­‐Gastaut patients Corny J, Papon A, Bellavoine V, Storme T, Merdariu D, Ilea A, Bourdon O, Auvin S. Pediatric Neurology & Pharmacy Dpts, Robert Debré University Hospital, Paris, France -­‐ [email protected] O11 -­‐ 1866 Successful use of Fenfluramine as add-­‐on treatment in Dravet syndrome: A two year prospective follow up Ceulemans B, Neels P, Boel M, Jorens P, Lagae L. Antwerp University Hospital, Belgium -­‐ [email protected] O12 -­‐ 1838 CDKL5 mutations and antiepileptic drugs tolerability Magalhães C, Carrilho I, Ribeiro A, Chorão R, Santos M. Centro Hospitalar do Porto, Portugal -­‐ c-­‐[email protected] O13 -­‐ 1691 High dose (4 mg/kg/day) versus usual dose (2 mg/kg/day oral prednisolone in the treatment of infantile spasms: a randomized open trial Prabaharan C, Aneja S, Sharma S, Seth A. Lady Hardinge Medical College, New Delhi, India -­‐ [email protected] 2 Parallel session 3: Mitochondrial disorders Chairs: Linda De Meirleir and Ingrid Tein O14 -­‐ 1917 Hypomyelination with brain stem and spinal cord involvement and severe leg spasticity (HBSL): Mutations in DARS are responsible Wolf NI, van der Knaap MS, de Coo IFM, Vanderver A, Leventer RJ, Damiani S,Simons C, Juneja M, Verma IC, Prabhakar P, Blaser S,Raiman J, Abbink TEM, Taft R. Dept. of Child Neurology, VU University Medical Center, Amsterdam -­‐ [email protected] O15 -­‐ 2036 Early onset mitochondrial encephalomyopathy with pulmonary hypertension due to [Fe-­‐S] cluster deficiency Abela L, Rohrbach M, Häberle J, Mayr H, Ahting U, Nuoffer JM, Scheer I, Bauer A, Hug M, Klauwer D, Plecko B Department of Child Neurology, Childrens Hospital, University of Zürich -­‐ [email protected] O16 -­‐ 1908 A homozygous mutation in IB57 involved in intramitochondrial iron-­‐sulfur cluster synthesis causes severe encephalopathy and mypathy in two neonates Vanlander A, Wilbrecht C, Ajit Bolar N, Smet J, De Paepe B, De Latter E, Van Laer L, Loeys B, Lill R, Van Coster R Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Gent, Belgium -­‐ [email protected] O17 -­‐ 1786 Exome Sequencing Reveals Heterozygous Mutations in the ADCK3 Gene in Siblings with Cerebellar Atrophy but Extreme Phenotypic Variability Blumkin L, Silver-­‐Leshinsky E, Zerem A, Yosovich K, Jalas C, Lev D, Lerman-­‐Sagie T. Metabolic Neurogenetic Service, Pediatric Neurology Unit, Wolfson Medical Center, Holon, Sackler School of Medicine, Tel-­‐Aviv University, Tel-­‐Aviv, Israel -­‐ [email protected] 018 -­‐ 1777 Thiamine transporter-­‐2 deficiency: a reversible cause of encephalopathy in children Pérez-­‐Dueñas B, Ortigoza JD, Serrano M, Fons C, Muchart J, Rebollo M, Molero M, Casado M, Artuch R. Department of Child Neurology, Sant Joan de Déu Hospital, University of Barcelona, Spain, and CIBER-­‐ER, ISCIII, Spain -­‐ [email protected] O19 -­‐ 1664 Succinyl-­‐CoA ligase deficiency: report on the first patient resulting from a combined defect in SUCLG1 and SUCLG2 genes Zafeiriou DI, Batzios S, Vargiami E, Willemsen M, Morava E, van den Heuvel L, Smet J, Van Coster R, Seneca S, Wanders R, Waterham H, Wevers R. 1st Department of Pediatrics, Aristotle University of Thessaloniki, Greece -­‐ [email protected] O20 -­‐ 1660 Leigh syndrome: a multicenter study of natural history Sofou K, de Coo IF, de Angst IB, Isohanni P, Pihko H, Östergaard E, Naess K, De Meirleir L, Tzoulis C, Uusimaa J, Mankinen K, Bindoff LA, Tulinius M, Darin N. Mitochondrial Clinical and Research Network (MCRN), Sweden -­‐ k[email protected] O21 -­‐ 1552 Biotin-­‐responsive basal ganglia disease revisited: Clinical, radiologic, and genetic findings Tabarki Melaiki B, Al Hashem A, Al Shafi S, Al Shahwan S, Zuccoli G. Department of Pediatrics, PSMMC, Riyadh, Saudi Arabia -­‐ [email protected] O22 -­‐ 1585 New insights into the spectrum of phenotypes and genotypes in Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) Hamilton EM, van Berge L, Steenweg ME, Linnankivi T, Uziel G, Krägeloh-­‐Mann I, Brautaset NJ, Andrews I, de Coo IF, van Berkel CG, Polder E, Scheper GC VUMC Amsterdam, The Netherlands -­‐ [email protected] 12:30 -­‐ 13:30 Lunch and lunch symposia Lunch symposium Genzyme Silver Room Lunch symposium Viropharma Copper Room Lunch symposium PTC Therapeutics Gold room 3 13:30 -­‐ 14:30 Selected Poster Presentations 1 -­‐ 4 PP1 Cerebral palsy, neonatology, stroke chair: Lars Palm PP2 Epilepsy 1 chair: Peter Baxter PP3 Neuromuscular and movement disorders chair: Michèl Willemsen PP4 Neurometabolic disorders chair: Rudy Van Coster 13:30-­‐14:30 DEM-­‐CHILD Teaching Seminary Silver room Clinical presentation of NCLS R. Williams, A Simonati NCL Genetics and diagnostic Algoritm A. Schulz Therapeutic perpectives and Palliative care A. Kohlschütter 14:30 -­‐ 16:00 Plenary session 2: Neuromuscular Disorders Gold Room Chairs: Gunnar Buyse and Thomas Sejersen IL 6 Integrated omic procedures in childhood neuromuscular diseases: New approaches to diagnostics and biomarkers -­‐ Eric P. Hoffman IL7 Outcome measures in childhood neuromuscular disorders: New concepts and standards -­‐ Eugenio Mercuri IL 8 Gene-­‐derived therapeutic approaches for childhood neuromuscular diseases -­‐ Nathalie Goemans 16:00 -­‐ 16:30 Coffee break and poster viewing 16:30 -­‐ 18:00 Parallel sessions 4-­‐6 Parallel session 4: Epilepsy and Cognitive Functions Chairs: Bernhard Schmitt and Daniele Hasaerts IL 9 Cognitive functions after epilepsy surgery -­‐ Helen Cross IL 10 Cognitive dysfunction in idiopathic epilepsy -­‐ Eliane Roulet-­‐Perez IL 11 Outcome in West Syndrome -­‐ Zvonka Rener Paralel session 5: Immunology and infectious diseases Chairs: Banu Anlar and Nina Barisic O23 -­‐ 1732 Childhood relapsing immune-­‐mediated polyneuropathy and hemolysis is associated with CD59 deficiency Nevo Y, Ben Zeev B, Tabib A, Straussberg R, Anikster Y, Shorer Z, Fattal-­‐Valeski A, Ta Shma A, Aharoni S, Rabie M, Zenvirt S, Goldshmidt H, Fellig Y, Shaag A, Mevorach D, Elpeleg O. Hadassah, Hebrew Univerisity Medical Center, Jerusalem -­‐ [email protected] 4 O24 -­‐ 1725 Autonomic dysfunction in children with Guillain-­‐Barré syndrome Aziz M, Watson L, Plant N, Vassallo G. Department of paediatric neurology, Royal Manchester children’s hospital, Oxford road, Manchester, UK -­‐ [email protected] O25 -­‐ 2018 Risks of Relapse and Severe Outcome in Children with a Clinically Isolated Acute Transverse Myelitis at Onset: a French-­‐British collaborative study Deiva K, Absoud M, Niotalkis G, Hemingway C, Lim M, Tardieu M. Department of Pediatric Neurology, National Referral Centre for Neuro-­‐Inflammatory Diseases in Children, Hôpitaux Universitaires Paris-­‐Sud, Le Kremlin Bicêtre -­‐ [email protected] O26 -­‐ 1915 Immunological studies in Rapid-­‐onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome Biancheri R, Napoli F, Calcagno A, Ceccherini I, Hacohen, Jacobson L, Lang B, Vincent A, Maghnie M. Child Neurology and Psychiatry Unit, Department of Neuroscience, Istituto Giannina Gaslini, Genova, Italy -­‐ [email protected] O27 -­‐ 2082 Anti-­‐myelin oligodendrocyte glycoprotein antibody positivity in children with demyelinating episodes James S, Hughes SE, Flynn P, Smyth G, McKinstry S, Rennie I, Hanrahan D, Peake D, Tirupathi S. Department of Neurology, Royal Belfast Hospital for Sick Children, Belfast, UK. -­‐ [email protected] O28 -­‐ 1989 Children in England with narcolepsy during the H1N1 (swine ‘flu) pandemic: clinical features in those receiving AS03 adjuvanted pandemic A/H1N1 (2009) influenza vaccine and in unvaccinated cases Winstone AM, Stellitano L, Verity CM, Shneerson JM, Andrews N, Stowe J, Miller E. Addenbrookes Hospital Cambridge UK -­‐ [email protected] O29 -­‐ 1951 Childhood encephalitis: epidemiological, clinical and radiological characteristics and their impact on the outcome Liptai Z, Ujhelyi E, Mihaly I, Barsi P, Szent Laszlo Hospital, Dept. of Paediatrics, Budapest, Hungary -­‐ [email protected] O30 -­‐ 1893 Guillain-­‐Barré syndrome in UK children: H1N1 vaccinations, preceding infections and clinical features Verity C, Addenbrookes Hospital, Cambridge, UK -­‐ [email protected] Paralel session 6: Cerebral palsy Chairs: Florian Heinen and Bernard Dan O31 -­‐ 1568 Neonatal neuroimaging predicts recruitment of contralesional corticospinal tracts following perinatal brain injury van der Aa NE,Verhage CH, Groenendaal F, Vermeulen RJ ,de Bode S, van Nieuwenhuizen O, de Vries LS. Dep of Neonatology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands -­‐ [email protected] O32 -­‐ 1912 Brain volume reduction in young adults with perinatal hypoxic-­‐ischaemic encephalopathy Bregant T, Rados M, Vasung L, Zadnik V, Derganc M, Evans AC, Neubauer D Kostovic I. Department of Pediatric Neurology, University Children’s Hospital, University Medical Centre Ljubljana, Slovenia -­‐ [email protected] O33 -­‐ 2123 Visual spatial perceptual profiles in children with Developmental Coordination Disorder or in very premature children with Cerebral Palsy Gonzalez Monge S, Praticien Hospitalier, Lyon, France -­‐ sibylle.gonzalez-­‐[email protected]­‐lyon.fr O34 -­‐ 1931 Innovative application of the motion graph deviation indexes for the quantification of the pre-­‐post BTX -­‐ A upper limb movement changes Darras N, Vanezis T, Tziomaki M, Pasparakis D and Papavasiliou A. Elepap Gait Analysis And Motion Analysis Center, Athens, Greece -­‐ [email protected] 5 O35 -­‐ 1861 Cerebral Visual Impairment and Cerebral Palsy: two sides of the same coin? Fazz E, Galli J, Micheletti S, Rossi A, Franzoni A. Civil Hospital -­‐ Brescia Ð, Italy -­‐ elis[email protected] O36 -­‐ 2035 Clinical Correlation of Arcuate Fasciculus Lateralization in Developmental Dysphasia Komárek V, Vydrová R, Kynèl M, Šanda J, Vránová M, Štìrbová K, Kršek P. Department of Child Neurology, Department of Radiology, Charles University Hospital Motol, Prague, Czech Republic -­‐ [email protected] O37 -­‐ 1898 Use of serious gaming to increase motivation of cerebral palsy children during rehabilitation Bonnechère B, Jansen B, Omelina L, Da Silva L, Mougeat J, Heymans V, Vandeuren A, Rooze M, Van Sint Jan S, Laboratory of Anatomy, Biomechanics and Organogenesis (LABO), Université Libre de Bruxelles, Belgium -­‐ [email protected] O38 -­‐ 1645 Brain lesions relate to gait pathology in children with unilateral and bilateral cerebral palsy Van Gestel L, Ortibus E, Meyns P, De Cock P, Sunaert S, Feys H, Duysens J, Jaspers E, Desloovere K. Dep. of Rehabilitation Sciences, Fac. of Kinesiology and Rehabilitation Sciences, KULeuven, Belgium -­‐ [email protected] 18:00 -­‐ 19:30 EPNS Academy of Pediatric Neurology : Childhood Stroke Gold Room Chairs: Inge Krageloh-­‐Mann and Lieven Lagae Clinical presentation and outcome Maja Steinlin Imaging and diagnostic guidelines Kees Braun Etiology and treatment options Vijeya Ganesan Thursday 26 September 2013 07:30 -­‐ 08:15 Early rise sessions 4-­‐6 ERS 4: Difficult to classify paroxysmal events Gunnar Buyse -­‐ Berten Ceulemans ERS 5: Neonatal EEG / AEEG Daniele Hasaerts -­‐ Geraldine Boylan ERS 6: Spasticity diagnosis and management Bernard Dan -­‐ Jean-­‐Paul Misson 08:30 -­‐ 10:00 Plenary Session 3: Epileptic Encephalopathies Gold Room Chairs: Berten Ceulemans and Coriene Catsman IL 12 New genes in early onset epileptic encephalopathy -­‐ Rima Nabbout IL 13 Animal models and Pathophysiology of epileptic encephalopathy -­‐ Aristea Galanopoulou IL 14 Treatable neonatal epilepsies -­‐ Barbara Plecko 6 10:00 -­‐10:30 Coffee break and poster viewing 10:30 -­‐ 12:15 Parallel Sessions 7-­‐9 Parallel Session 7: Combined EPNS / EACD session: Up-­‐to-­‐date management Cerebral Palsy Chairs: Jean Paul Misson and Dana Craiu IL 15 Multidisciplinary assesment -­‐ Bernard Dan IL 16 Botulinum toxin therapy -­‐ Antigone Papavassiliou IL 17 Deep Brain Stimulation -­‐ Jean-­‐Pierre Lin Parallel session 8: Neurogenetic Disorders Chairs: Marie Cecile Nassogne and Paolo Curatolo O39 -­‐ 1826 Natural course of pontocerebellar hypoplasia type 2 Sánchez-­‐Albisua I, Frölich S, Krägeloh-­‐Mann I. University Children’s Hospital, Tübingen, Germany -­‐ [email protected]­‐tuebingen.de O40 -­‐ 2159 Hypomyelinating leukodystrophy due to recessive mutations of GJC2 (connexin 47): clinical and radiological characteristics in 18 patients Renaldo F, Tonduti D, Dorboz I, Masliah J, Giraud, G, Elmaleh M, Orivoli S, Beraud-­‐Majorel C, Drunat S, Chalard F, Barthez M A, Desguerre I, Quijano-­‐Roy S, Rodriguez D, Boespflug-­‐Tanguy O, Centre de Référence des Leucodystrophies, Service de Neuropédiatrie et Maladies Métaboliques; Hôpital Robert Debré, AP-­‐HP, Paris, France -­‐ [email protected] O41 -­‐ 1941 Mutation spectrum and clinical characteristics in Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-­‐ABC) Hamilton EM, Vanderver A, Siriwardena K, Pinelli L, Schiffmann R, Blaser S, Naidu S, van Berkel CG, Polder E, Abbink TE, Wolf NI, van der Knaap MS VUMC, Amsterdam, The Netherlands -­‐ [email protected] O42 -­‐ 1909 FOXG1 gene: phenotype Ðgenotype relation in Spanish patients Pineda Marfa M, O’Callaghan Gordo M, Gerotina Mora E, Quandt Herrera E, Rabaza Gairí M, Brandi Tarrau N; Cortès Saladelafont E, Roche Martínez A, Armstrong Morón J. Fundació Hospital Sant Joan de Déu and CIBERER, ISCIII1. Servei Neuropediatra y genética molecular. Hospital Sant Joan de Deu2, Barcelona. Spain -­‐ [email protected] O43 -­‐ 1896 The neurology of rhizomelic chondrodysplasia punctata Bams-­‐Mengerink AM, Koelman JHTM, Waterham H, Barth, PG, Poll-­‐The, BT Academic Medical Centre, Amsterdam, The Netherlands -­‐ [email protected] O44 -­‐ 1703 Deficiency of the E3 ubiquitin ligase TRIM2 causes early-­‐onset axonal neuropathy Ylikallio E, Pöyhönen R, Hilander T, Paetau A, Lönnqvist T, Tyynismaa H. Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland -­‐ [email protected] O45 -­‐ 1612 RATE: randomised clinical trial of rapamycin in children with Tuberous Sclerosis Complex and intractable epilepsy Overwater IE, Rietman A, Bindels-­‐de Heus GCB, Moll HA, Elgersma Y, Wit MCY Neurology, Neuroscience; ENCORE Expertise centre for neurodevelopmental disorders -­‐ [email protected] O46 -­‐ 1548 Long term follow-­‐up of clinical and neurographical abnormalities in eight Croatian patients with triple A syndrome 7 Barisic N, Dumic M, Kusec V, Lehman I, Bunoza B, Grdjan P, Ivanja V. Department of Pediatrics, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, Zagreb, Croatia -­‐ [email protected] O47 -­‐ 1530 Outcome of surgical treatment of 64 TSC-­‐associated subependymal giant cell astrocytomas Kotulska K, Roszkowski M, Mandera M, Daszkiewicz P, Grajkowska W, Jurkiewicz E, Borkowska J, Jozwiak S. The Childrens Memorial Health Institute, Warshaw Poland -­‐ [email protected] Parallel session 9: Varia Chairs: Vladimir Komarek and Colin Kennedy O48 -­‐ 1975 The Presenting Features of Arterial Ischaemic Stroke in a Population-­‐Based Cohort Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, Parker AP, Wassmer E, Wraige E, Amin, Edwards HB, O’Callaghan FJ. University of Bristol, UK -­‐ [email protected] O49 -­‐ 2118 A clinical advisory board for a rare disease (Prader-­‐Willi syndrome) Blichfeldt S, Farholt S. Herlev University Hospital, Pædiatric Department, 2730 Herlev Denmark -­‐ [email protected] O50 -­‐ 1933 Normative data of the 6-­‐minute walk test in healthy boys aged 5-­‐12 years and correlations with anthropometric variables and myometry Goemans N, Klingels K, Boons S, Verstraete L, Peeters C, van den Hauwe M, Feys H, Buyse G. Child Neurology, University Hospitals Leuven, Leuven, Belgium -­‐ [email protected] O51 -­‐ 2115 Clinical Presentation and genetic causes of Charcot Marie Tooth Disease in a Paediatric Cohort Niermeijer JMF, Rustenburg L, Van Ruissen F, Verhamme C, Baas F, Poll-­‐The, B. Academic Medical Centre, University of Amsterdam, The Netherlands -­‐ [email protected] O52 -­‐ 2063 Spectrum of cerebellar and anterior horn cell degeneration caused by EXOSC3 mutations Burglen L, Nguyen S, Cances C, Cuisset JM, Julia S, Metreau J, Lion-­‐François L, Legall A, Amsallem D, Gelot A, Billette de Villemeur T, Rodriguez D. Reference center for cerebellar malformations and congenital diseases and Department of genetics, AP-­‐HP, Hôpital Trousseau and INSERM U676, Paris, France -­‐
[email protected] O53 -­‐ 1995 Long-­‐term Outcome after Vegetative State due to Near-­‐Drowning and Quality of Life of the Families Kluger G, Kirsch A, Hessenauer M, Lahl O, Steinbeis von Stülpnagel C, Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schöen Klinik Vogtareuth Germany -­‐ [email protected]­‐kliniken.de O54 -­‐ 1853 Manifestations of Cowden syndrome in childhood Schieving JH, Padberg GWAM, Willemsen MAAP. Radboud University Hospital Nijmegen, Department of Pediatric Neurology Nijmegen, The Netherlands -­‐ [email protected] O55 -­‐ 1566 Incidental white matter lesions in children presenting with headache Bayram E, Topcu Y, Karaoglu P, Yis U, Cakmakci HG, Hiz SK Dokuz Eylul University Hospital, Division of Pediatric Neurology Izmir, Turkey -­‐ [email protected] O56 -­‐ 1721 The role of probabilistic tractography in the surgical treatment of pediatric brainstem gliomas Máté A, Kis D, Vörös E, Barzó P. Department of Neurosurgery, University of Szeged, Szeged, Hungary -­‐ [email protected] 12:30 -­‐ 13:30 Lunch and lunch symposia Lunch symposium Biomarin Copper room Lunch symposium Novartis Silver Room Lunch symposium EISAI Europe Gold Room 8 Friday 27 September 2013 07:30 -­‐ 08:15 Early rise sessions: 7-­‐9 ERS 7: Functional Brain Imaging Xavier De Tiège -­‐ Margot Taylor ERS 8: Advances in Genetic Diagnosis Anna-­‐Elina Lehesjoki -­‐ Jeroen Breckpot ERS 9: Sleep disorders Patrick Van Bogaert -­‐ Sonja Scaillet 08:30 -­‐ 10:00 Plenary Session 4: Auto-­‐immune disorders Gold room Chairs: Marc Tardieu and Colin Kennedy IL 18 Auto-­‐immune Encephalitis -­‐ Joseph Dalmau IL 19 Autoimmune CNS disorders in primary immune deficiencies -­‐ Banu Anlar IL 20 The spectrum of anti-­‐myelin oligodendrocyte glycoprotein antibody associated demyelinating diseases in children -­‐ Kevin Rostasy 10:00 -­‐ 10:30 Coffee Break and poster viewing 10:30 -­‐ 12:15 Parallel Sessions 10-­‐12 Parallel session 10: Movement disorders 2 Chairs: Mary King and Sameer Zuberi IL 21 Mary King IL 22 Sameer Zuberi O57 -­‐ 1880 Progressive ataxia, hyperkinetic movement disorder with myoclonic jerks and falls in a toddler: think of cerebral folate deficiency! Toelle SP, Wille D, Schmitt B, Scheer I, Thöny B, Plecko B. University Children’s Hospital Zurich, Division of Neurology Switserland -­‐ [email protected] O58 -­‐ 2017 Gabapentin can improve dystonia severity, transfers, sitting, sleep, mood and pain in children Liow N, Marianczak J, Kirk E, Tomlin S, Lumsden D, Gimeno H. Kaminska M, Perides S, Lin JP. Complex Motor Disorders Service Children’s Neurosciences Centre, Evelina Children’s Hospital, Guy’s and St. Thomas’ NHS Foundation Trust UK -­‐ [email protected] O59 -­‐ 1906 Alternating hemiplegia and ATP1A3 gene: evolution of 12 cases into adulthood Genotype-­‐Phenotype correlations. Ramirez-­‐Camacho A, Panagiotakaki E, Poncelin D, Nicole S, Lesca G, Arzimanoglou A. Epilepsy, Sleep and Paediatric Neurophysiology Dpt., Femme Mère Enfant Hospital, University Hospitals of Lyon (HCL), France -­‐ [email protected] 9 O60 -­‐ 1707 Ataxia and areflexia precede progressive myoclonus ataxia in young children with GOSR2 mutation van Egmond ME, Verschuuren-­‐Bemelmans CC, Nibbeling EA, Eltin JW, Sival DA, Brouwer OF, de Vries JJ, Kremer HP, Sinke RJ, Tijssen MA, de Koning TJ. Department of Neurology, University of Groningen, University Medical Center Groningen, The Netherlands-­‐ [email protected] O61 -­‐ 1802 Tyrosine hydroxylase deficiency. The Greek Experience Pons R, Syrengelas D, Gkika A, Dinopoulos A, Orfanou I, Serrano M, Artuch R, Youroukos S, Agia Sofia Hospital Athens Greece -­‐ [email protected] Parallel session 11: Neurometabolic disorders Chairs: Rudy Van Coster and Marjo Van der Knaap O62 -­‐ 1673 The Natural History of Late Infantile CLN2 Disease: Striking Homogeneity of Clinical Progression in Two Independently Obtained Large Clinical Cohorts Schulz A, Nickel M, Downs M, Mezey J, Landy H, Sondhi D, Jacoby D, Wittes J, Crystal R, Kohlschuetter A Children’s Hospital, University Medical Center Hamburg-­‐Eppendorf, Hamburg, Germany -­‐ [email protected] O63 -­‐ 1788 Diagnosing the tip of an iceberg in a potentially treatable neurometabolic disorder: cerebral creatine deficiency syndromes Haliloglu G, Oguz KK, Onol S, Tokatli A, Coskun T, Topcu M. Hacettepe University Children’s Hospital, Department of Pediatric Neurology -­‐ [email protected] O64 -­‐ 1920 Zellweger spectrum manifestations in adulthood Berendse K, Engelen M, Wanders RJA, Waterham HR. Poll-­‐The BT. Department of Paediatric Neurology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands -­‐ [email protected] O65 -­‐ 1997 Hematopoietic stem cell transplantation in juvenile metachromatic leukodystrophy Groeschel S, Bley A, Kühl JS, Kehrer C, Müller I, Kohlschütter A, Weschke B, Krägeloh-­‐Mann I. Department of Pediatric Neurology & Developmental Medicine, University Children’s Hospital, Tübingen, Germany -­‐ [email protected]­‐tuebingen.de O66 -­‐ 1608 Hypomyelination and congenital cataract: three additional patients carrying novel mutations Biancheri R, Traverso M, Rossi A, Gazzerro E, Assereto S, Baldassari S, Fruscione F, Abdalla EM, Fassad MR, Ruffinazzi G, Savasta S, Zara F, Minetti C. Department of Neuroscience, Istituto Giannina Gaslini, Genova, Italy -­‐ [email protected] O67 -­‐ 2165 Phenotypical variation in vanishing white matter disease van der Lei HDW, Gerver JAM, van Berkel CGM, van der Knaap MS. Child Neurology, VU University Medical Center, Amsterdam the Netherlands -­‐ [email protected] O68 -­‐ 2091 Neurological phenotypes in Niemann-­‐Pick type C disease: unraveling an overlooked neurometabolic disorder Lourenço CM, Van der Linden V, Bonfim D, Ribeiro E, Marques Jr W. University of Sao Paulo, Sao Paulo, Brazil -­‐ [email protected] O69 -­‐ 1973 MRI in the diagnosis of peroxisomal disorders when laboratory tests fail van der Knaap MS, Ferdinandusse S, Vanderver A. Child Neurology, VU University Medical Center, Amsterdam -­‐ [email protected] O70 -­‐ 1720 Brain Volumetry and Clinical Scoring in Patients with CLN2 Disease: A Diagnostic Tool to Monitor Disease Progression Löbel U, Nickel M, Nestrasil I, Sedlacik J, Kohlschütter A, Schulz A. Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-­‐Eppendorf, Hamburg, Germany -­‐ [email protected] 10 O71 -­‐ 2078 Brain gene therapy for Metachromatic Leukodystrophy Sevin C, Roujeau T, Piguet F, Sondhi D, Colle MA, Raoul S, Deschamps JY, Bouquet C. Inserm U986 Paris, Hopital Bictere, France -­‐ [email protected] inserm.fr Parallel session 12: Fetal and neonatal neurology Chairs: Marc D’Hooghe and Linda De Vries O72 -­‐ 1702 Concordance between Head Circumference Growth and Neurological Impairment among four Clinical Presentations of Microcephaly Coronado R, Giraldo J, Macaya A, Roig M. Hospital de Terrassa, Catalonia, Spain -­‐ [email protected] O73 -­‐ 1935 SBA and Control Muscle Ultrasound Density From Pre-­‐ to Postnatal Life Verbeek RJ, Sollie KM, Mulder PB, van der Hoeven JH, Hoving EW, Sentner CP, Sival DA. Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands -­‐ [email protected] O74 -­‐ 2025 Benefits of universal newborn screening for permanent childhood hearing impairment to reading comprehension in adolescence: early confirmation of deafness matters Kennedy CR, Pimperton H, Chorozoglou M, Kreppner J, Mahon H, Powers SG, Peacock J, Stevenson JE, Terlektsi M, Worsfold SM, Yuen HM. Southampton General Hospital, Southhampton, UK -­‐ [email protected] O75 -­‐ 1987 Specific impairment of functional connectivity between language regions in former early preterms Wilke M, Hauser T-­‐K, Krägeloh-­‐Mann I, Lidzba K. Department of Pediatric Neurology & Developmental Medicine, University Children’s Hospital Tübingen, Germany -­‐ [email protected]­‐tuebingen.de O76 -­‐ 1901 Neurodevelopmental outcomes of newborns requiring a brain MRI: A retrospective study Papandreou A, Poulton C, Kermode R, Ramesh CA. West Hertfrodshire Hospitals NHS Trust, Watford General Hospital, Watford, UK -­‐ [email protected] O77 -­‐ 1605 Thrombophilic genes polymorphisms in children with perinatal brain injury Baranov DA, Lvova OA, Kuznetsov NN, Kovtun OP, Plaxina AN, Kolmogortseva VD. City’s Perinatal Center, Russia -­‐ [email protected] O78 -­‐ 1870 Neuro-­‐imaging and Neurodevelopmental outcome in Preterm infants with a Periventricular Haemorrhagic Infarction located in the Temporal and Frontal lobe Soltirovska Salamon A, Groenendaal F, Van Haastert IC, Rademaker CM, Benders MJ, Koopman-­‐Esseboom C, de Vries L. Department of Neonatology, Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, The Netherlands -­‐ [email protected] O79 -­‐ 1599 Prognostic value of conventional EEG in asphyxiated term newborns treated with Hypothermia: experience in 20 cases Aeby A, Khabbache K, Van Overmeire B, Vermeylen D, Van Bogaert P. Pediatric Neurology, Erasme-­‐Hospital-­‐ULB. [email protected] O80 -­‐ 1570 Cognitive outcome in childhood following unilateral perinatal brain injury van der Aa NE, lvan Buuren LM, Dekker HC, Vermeulen RJ, van Nieuwenhuizen O, van Schooneveld MMJ, de Vries LS. Department of Neonatology, Wilhelmina ChildrenÕs Hospital, Utrecht, The Netherlands -­‐ [email protected] 12:30 -­‐ 13:30 Lunch and lunch symposia Lunch symposium Cyberonics Copper room Lunch symposium Actelion Silver room 11 13:30 -­‐ 14:30 PP5 PP6 PP7 PP8 Selected Poster presentations 5-­‐8 Varia (sleep, oncology, trauma) chair: Richard Newton Neurogenetic and mitochondrial disorders chair: Haiki Rantala Epilepsy 2 chair: John Stephenson chair: Günter Bernert Learning dirsorders / Immunology 13:30-­‐14:30 Round table on sulthiame in childhood epilepsy Chair: T. Lerman-­‐Sagie Silver Room 14:30 -­‐ 16:00 Plenary session 5: Treatment of Neurometabolic disorders Gold Room Chairs: Barbara Plecko and Linda De Meirleir Session dedicated to Gilles Lyon IL 23 Treatment of the Monoamine Neurotransmitter Disorders -­‐ Manju Kurian IL 24 Treatment of Mitochondrial Diseases -­‐ Ingrid Tein IL 25 Treatment of neurodegeneration with brain iron accumulation (NBIA) -­‐ Susan Hayflick 16:00 -­‐ 16:30 Coffee break and poster viewing 16:30 -­‐ 18:15 Parallel sessions 13-­‐15 Parallel session 13: Combined EPNS / ICNA session Chairs: Pratibha Singhi -­‐ Sergio Rosemberg IL 26 HIV and Paediatric Neurology -­‐ Jo Wilmshurt IL 27 Malaria and Paediatric Neurology -­‐ Charles Newton IL 28 Paediatric Neurology in Africa -­‐ Michael Boele van Hensbroek Parallel session 14: Learning disabilities, ADHD and autism Chairs: Patrick Berquin and Sergiusz Jozwiak O81 -­‐ 1871 Motor cortical inhibition in ADHD: modulation of the transcranial magnetic stimulation-­‐evoked N100 during a go/nogo task D’Agati E, Hoegl T, Dippel G, Curatolo P, Bender S, Kratz O, Moll GH, Heinrich H. University Hospital of Erlangen, Germany, Tor Vergata University, Rome, Italy -­‐ [email protected] O82 -­‐ 1582 Preliminary data on the use of cigarettes, alcohol and drugs in a follow-­‐up study of adolescents with Tourette Syndrome Groth C, Debes N, Skov L. Pediatric Department, Herlev University Hospital, Denmark -­‐ [email protected] O83 -­‐ 2038 Do rolandic spikes on EEG at ADHD assessment influence on ADHD subtype and the use of methylphenidate for ADHD? Socanski D, Herigstad A. Stavanger University Hospital, Norway -­‐ [email protected] 12 O84 -­‐ 1965 Improving Motor Learning in a Rat Model of ADHD Soderlund GBW. Norway -­‐ [email protected] O85 -­‐ 1992 Cortico-­‐vocal coherence in autism spectrum disorders Suarez Garcia S, Clumeck C, Bourguignon M, Wens V, Op de Beeck M, Marty B, Soncarrieu M, Deconinck N, Delvenne V, Goldman S, Van Bogaert P, De Tiège X. Université Libre de Bruxelles, Laboratoire de Cartographie Fonctionnelle du Cerveau Belgium -­‐ [email protected] O86 -­‐ 1830 Cognitive functions in school-­‐children with frontal or temporal epilepsy -­‐ the long term study Mazurkiewicz-­‐Beldzinska M, Kondracka J, Szmuda M, Matheisel A. Dept. of Developmental Neurology Medical University of Gdansk Poland -­‐ [email protected] O87 -­‐ 1771 Long-­‐term simvastatin treatment for cognition and daily life in children with Neurofibromatosis type 1; results from the NF1-­‐SIMCODA trial van der Vaart T, Plasschaert E, Rietman AB, Renard M, Oostenbrink R, Vogels A, de Wit MC, Descheemaeker MJ, Vergouwe Y, Catsman-­‐Berrevoets CE, Legius E, Elgersma Y, Moll HA. Department of Neuroscience; Department of Paediatrics; ENCORE Expertise centre for Neurodevelopmental disorders, Erasmus MC, Rotterdam, The Netherlands -­‐ [email protected] 088 -­‐ 1682 Effects of methylphenidate on functional networks activation in children with Attention Deficit Hyperactivity Disorder Berquin P, Querne L, Service de Fall S, Delignieres A, Simonnot A, Le Moing A-­‐G. Service de Neuropédiatrie & GRAMFC U1105, CHU Amiens France -­‐ [email protected]­‐picardie.fr O89 -­‐ 1600 Language development at 2 years is correlated to brain microstructure in the left superior temporal gyrus at term equivalent age: a diffusion tensor imaging study Aeby A, De Tiège X, David P, Balériaux D, Van Overmeire B, Metens T, Van Bogaert P. Pediatric Neurology and Laboratoire de Cartographie Fonctionnelle du Cerveau, UNI (Université Libre de Bruxelles -­‐ULB Neuroscience Institute) Erasme-­‐Hospital, Belgium -­‐ [email protected] Parallel session 15: Epilepsy Chairs: Sameer Zuberi and Oebele Brouwer O90 -­‐ 2157 Treatment of Electrical Status Epilepticus in Sleep (ESES): A systematic review and meta-­‐analysis Van den Munckhof B, Van Dee V, Liukkonen E, Sagi L, Loddenkemper T, Sánchez Fernández I, Braun KPJ, Jansen FE. Rudolf Magnus Institute of Neuroscience, Department of Paediatric Neurology, University Medical Center, Utrecht, The Netherlands -­‐ [email protected] O91 -­‐ 1581 Compensatory visual system adaptations after hemispherectomy in children Koenraads Y, van der Linden DCP, van Schooneveld MMJ, Imhof SM, Porro GL, Braun KPJ. Department of Ophthalmology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands -­‐ [email protected] O92 -­‐ 2108 The classification of epilepsies using the ILAE revised terminology and concepts for organization of seizures and epilepsies and ICD-­‐10 -­‐ challenges in clinical practice Iliescu C, Barca D, Budisteanu M, Burloiu C, Butoianu N, Minciu I, Motoescu C, Tarta-­‐Arsene O, Craiu D. „Carol Davila” University of Medicine, Department of Neurology, Pediatric Neurology, Neurosurgery, Psychiatry -­‐ Pediatric Neurology Clinic No.II, Bucharest; Al. Obregia Hospital, Bucha rest, Romania -­‐ [email protected] O93 -­‐ 2003 Different aspects in the evaluation of vagus nerve stimulation efficacy among children with therapy-­‐refractory epilepsy Orosz I, Buck E, Sperner J, Thyen U. Department of Neuropediatrics, Childrens’s Hospital, University of Lübeck, Germany -­‐ [email protected] 13 O94 -­‐ 1758 Cardiac and respiratory autonomic dysfunction in childhood epilepsy Jansen K, Varon C, Van Huffel S, Lagae L. Pediatric neurology, University Hospitals Leuven, Belgium -­‐
[email protected] O95 -­‐ 1739 Severe myoclonic epilepsy in infancy: clinical and neuropsychological analysis according to age at diagnosis of SMEI El M Kaddem B, Christiaens F, van Rijckevorsel F, Nassogne MC. Université catholique de Louvain, Cliniques universitaires Saint-­‐Luc, Bruxelles, Belgium -­‐ [email protected] O96 -­‐ 1638 Electrical status epilepticus in sleep (ESES): etiology, clinical picture and course Aleksandrova I, Bojinova V, Dimova P; Clinic of Child Neurology, “St. Naum” University Hospital of Neurology and Psychiatry, Sofia, Bulgaria -­‐ [email protected] O97 -­‐ 1635 Treatment of electrical status epilepticus in sleep (ESES): efficacy and unsolved questions Dimova P, Alexandrova I, Bojinova V. Clinic of Child Neurology, St. Naum University Hospital of Neurology and Psychiatry -­‐ [email protected] O98 -­‐ 1979 Intravenous methylprednisolone for the treatment of infantile spasms Aburahma A, Al-­‐Sharqawi S. Jordan -­‐ [email protected] 18:15 -­‐ 19:00 Meet the expert session : sessions where delegates can meet experts to ask advice on specific cases Movement disorders Emilio Alvarez Fernandez Epilepsy Alexis Arzimanoglou Hereditary polyneuropathies Peter De Jonghe Saturday 28 September 2013 08:30 -­‐ 09:00 General Assembly EPNS 09:00 -­‐ 11:00 Special Symposium: The Future of Paediatric Neurology Chairs: Florian Heinen and Peter Baxter IL 29 Gene therapy strategies for genetic leucodystrophies -­‐ Nathalie Cartier-­‐Lacave IL 30 Stem Cell therapy in paediatric neurology -­‐ Pierre Vanderhaegen IL 31 Closed Loop Treatment Systems in Epilepsy -­‐ Lieven Lagae IL 32 Diagnostics in new white matter diseases -­‐ Marjo van der Knaap Gold Room Gold room 14 11:00 -­‐ 12:00 Highlights in Paediatric Neurology organized by the EPNS board Closing ceremony 15 ABSTRACTS 1. ORAL PRESENTATIONS Wednesday 25 September 2013 Parallel session 1: Movement Disorders Chairs: Michèl Willemsen and Emilio Alvarez Fernandez O1 -­‐ 1990 Clinical Spectrum of Dopamine Transporter Deficiency Syndrome: from infantile parkinsonism-­‐dystonia to juvenile parkinsonism Ng J, Li Y, Zhen J, Kakar N, Ahmad J, Thiele H, Kubisch C, Rider N, Strauss K, Holmes-­‐Morton D, D’Agnano D Anikster Y, Carducci C, Hyland K, Rostein M, Leuzzi V, Borck G, Reith MEA, Kurian MA. Neurosciences, Institute Child Health-­‐UCL, UK -­‐ [email protected] Objective: Dopamine transporter deficiency syndrome (DTDS) is a newly described neurotransmitter disorder that presents with progressive infantile onset parkinsonism-­‐dystonia.[1] It is characterized by raised CSF homovanillic acid: 5-­‐hydroxyindoleacetic acid (HVA: HIAA) ratio of>5.0. It is caused by pathogenic mutations in SLC6A3 that encodes for the dopamine transporter (DAT). In order to better define this disorder, we describe new clinical phenotypes, novel genotypes and in vitro functional studies in a new cohort of DTDS patients. Methods: Patients presenting with parkinsonism and/or dystonia associated with a raised CSF HVA: HIAA were identified. SLC6A3 mutational analysis was performed, with in vitro functional studies of all identified missense mutations. Results: Eight patients were identified (5 males) from 5 unrelated families. Four presented with a progressive movement disorder from childhood but four presented with a juvenile parkinsonian phenotype and prominent tremor (currently aged 16-­‐ 34 years). The diagnosis was delayed in all cases (range 0.5-­‐33 years) post-­‐
onset of symptoms. Mutation screening of SLC6A3 revealed novel, previously unreported mutations in all patients (missense and splice site mutations). In vitro functional studies demonstrated that mutant DAT showed reduced dopamine uptake with reduced dopamine binding affinity, surface binding and substrate recognition. Immunoblotting studies implicate absent/impaired glycosylation of DAT and abnormal trafficking of DAT in DTDS. Conclusion: We report a cohort of patients with the classical features of DTDS [1] as well as identification of new DTDS patients with features of juvenile parkinsonism, thereby expanding the clinical disease phenotype. Functional analysis of mutant DAT implicates trafficking defects as a novel disease mechanism in DTDS. As a “cerebral palsy mimic”, we conclude that DTDS remains under-­‐recognised and misdiagnosed, leading to delayed diagnosis. The identification of adult DTDS patients suggests that neurotransmitter analysis and SLC6A3 testing should be considered in the neurological investigation of juvenile parkinsonism phenotypes. Reference: 1.Kurian MA. Lancet Neurol.2011;19(1):54-­‐62 O2 -­‐ 2122 Dystonia in previously well children-­‐ two years experience in a UK tertiary centre Pathak D, Whitney A, Forrest K, Kirkham F. University Hospitals Southampton -­‐ [email protected] Objectives: To report the results of investigation for acute dystonia and increase awareness of the possibility of anti-­‐NMDA encephalitis. Materials and Methods: The index case was a 4 year old child of Chinese origin who had recently moved from Hong Kong and presented with acute onset gait abnormality with falls and dystonic and choreiform movements. Few days later he developed mood swings and behavioural problems. There was no recent history of intercurrent illness. We audited 18 other cases of acute dystonia in previously well children who presented during 2011-­‐12. Results: The index case had normal inflammatory markers including ESR, ASOT, anti DNAse B and ANA. T2-­‐weighted MRI brain was normal. His blood was positive for anti-­‐ NMDA antibody while his identical twin brother, who had no movement disorder, was negative. He was treated with five days high dose Methyl Prednisolone followed by weaning course of Oral Prednisolone over four weeks. This resulted in resolution of his abnormal movements completely. His behaviour is improving. Of the 18 children with acute dystonia, 9 were girls. Median age was 13 (range 1-­‐16) years; Five (27%) had abnormal MRI in the form of high signal focus in caudate nucleus, Labrune Syndrome, high signal in both parietal lobes of uncertain significance, mild cerebral atrophy and iron deposition in basal ganglia. One had dopa-­‐responsive dystonia, one had previously diagnosed ADEM and another had non-­‐kinesogenic paroxysmal dyskinesia. Of 5 who had anti-­‐
16 Streptococcal antibodies, 3 had high anti-­‐ DNAse titre (>400). Three were tested for anti NMDA antibody; all were negative. Ten (55%) underwent genetic testing but no diagnoses have yet been made although 3 have family history. Conclusion: Acute dystonia in previously well children is common in Neurology practice. It is important to diagnose treatable causes including NMDA encephalitis and Dopa-­‐ responsive dystonia, as well as recognizing rare genetic forms. O3 -­‐ 2102 GLUT1 deficiency syndrome from infancy into adulthood: a follow-­‐up study Leen WG, Taher M, Mewasingh L, Willemsen Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands -­‐ [email protected] Background: GLUT1 deficiency syndrome (GLUT1DS) is a treatable neurometabolic disorder in which glucose transport into the brain is disturbed. Since the disorder is known for only two decades, little is known about the prognosis of GLUT1DS. Objective: Our purpose was to investigate the evolution of symptoms in patients with the classical, complex phenotype of GLUT1DS from infancy into adulthood. Methods: We have performed a systematic literature review as well as a cohort study, including adult GLUT1DS patients with a complex phenotype (aged 18 years and older). Results: The literature search yielded a total of 86 adult GLUT1DS patients of which 26 patients (30%) with a complex phenotype. Seven GLUT1DS patients with a complex phenotype were prospectively followed in our clinic from childhood into adulthood. In general, epilepsy was a prominent feature during infancy and childhood. During adolescence, however, epilepsy diminished or even disappeared, but new paroxysmal movement disorders such as paroxysmal exercise-­‐induced dyskinesia appeared. These paroxysmal movement disorders responded well to the modified Atkins diet (video). Conclusion: In general, in patients with a complex phenotype of GLUT1DS variation of symptoms over time is seen, with epilepsy as the most disabling symptom during childhood and movement disorders during adolescence or early adulthood. The modified Atkins diet is a good alternative for the ketogenic diet for the treatment of GLUT1DS related paroxysmal movement disorders in adolescents and adults. O4 -­‐ 2020 Electroneuromyography parameters in hereditary and congenital ataxia Milic Rasic V, Brankovic V, Mladenovic J , Kosac A, Todorovic S. Clinic for neurology and psychiatry for children and youth, Medical Faculty, University of Belgrade, Belgrade, Serbia -­‐ [email protected] Introduction: Early onset hereditary (HA) and congenital ataxia (CA) are heterogeneous group of disorders. Associated non-­‐cerebellar signs (pyramidal, extrapyramidal, cognitive, ocular, neuropathy) could be a clue in differentiating subtypes of HA and CA. Objectives: To examine the value of electroneuromyography (ENMG) studies in the diagnostic protocol of early onset ataxia subtypes. Material and methods: ENMG was performed in 40 patients (F:22; M:18) who were diagnosed (Friedreich ataxia 16; other subtypes of HA: 14 and CA: 10) at the Clinic for neurology and psychiatry for children and youth from 2002 to 2012. ENMG was performed on the Premier (Medelec) apparatus according to protocols DeLisa (2005). We analyzed amplitude of SNAP, SCV, motor TL, amplitude of CMAP and MCV in all patients, and needle EMG test in patients with abnormal motor conduction study. The mean duration of the disease at the ENMG test was 5.8±6.8 (0.5 – 27yr). SARA scale was used for determining score of cerebellar dysfunction. Molecular genetic tests: PCR for dynamic mutation and the direct sequencing in SACS and ANO10 genes were performed. Results: Neuropathy was detected in 25 (62.5%) patients. All patients with Friedreich ataxia (FA) had neuropathy, which was statistically significant with the other tested group (p<0,001). 50% patients (7/14) of non-­‐Friedreich HA and 20% of CA patients had a neuropathy, without statistically significant difference between them. Demyelinating neuropathy did not exist in any group. The most frequent subtype was sensory axonal neuropathy (almost all FA pt). Motor axonal neuropathy was present in 4 patients-­‐ 3 of them with ANO10 mutation. Sensory and motor axonal neuropathy was detected in 4 patients (two with define genotype-­‐ SACS and ATXN2 gene mutations). Conclusion: ENMG could be useful test in planning genetic study for hereditary and congenital ataxias, particularly in autosomal recessive forms. Parallel session 2: Epileptic encephalopathies Chairs: Raili Riikonen and Alec Aeby O5 -­‐ 1819 Impaired slow wave sleep downscaling in infantile spasms with hypsarrhythmia Fattinger S, Schmitt B, Bölsterli B, Critelli H, Jenni O, Huber R. University Children’s Hospital Zurich, Switserland -­‐ [email protected] 17 The epileptic encephalopathy West Syndrome is characterized in the EEG by multifocal spike waves and high amplitude slow frequency activity (hypsarrhythmia), which is most pronounced during non-­‐REM (NREM) sleep, and is often accompanied by developmental regression. The underlying pathophysiology of the encephalopathy is unknown and infantile spasms can be effectively treated with corticosteroids. In the epileptic encephalopathy ESES it was recently shown that the pathological changes in the sleep EEG impair sleep dependent renormalization of network synchronisation. In healthy individuals, neuronal synchronisation increases during the day, which is reflected in steep slow waves during initial NREM sleep, and decreases back to baseline level in the course of sleep. This renormalization of neuronal synchronicity is thought to be important for efficient learning the next day. We hypothesised that hypsarrhythmia may impair the renormalization of neuronal synchronicity in West Syndrome patients. We analysed retrospectively the overnight sleep EEG of 15 untreated patients (6 ± 2.4 months) with infantile spasms and hypsarrhythmia and two follow-­‐up nap recordings (under and after treatment with corticosteroids). Data were compared to healthy age and gender matched controls. In patients the overnight decrease of the slope of slow waves was reduced (p<.05) resulting in significantly steeper slope of slow waves towards the end of the night (p<.001). During the nap, under treatment the slope of slow waves was significantly reduced in patients compared to controls (p<.05). However, after the treatment period the slope was similar between patients and controls. In conclusion, our results show evidence for an impaired overnight reduction of neuronal synchronisation in West Syndrome patients. Such impaired sleep dependent renormalization of network synchronization may contribute to the developmental regression seen in these patients. Moreover, treatment with corticosteroids leads to a pronounced reduction of neuronal synchronicity, which might contribute to a normalization of network synchronization after treatment. O6 -­‐ 2105 KCNT1 mutations in a national cohort of children with migrating partial seizures of infancy McTague A, Meyer E, Appleton RE, Lascelles K, Desurkar A, Kneen R, Kurian Ma. Neurosciences unit UCL, London, UK -­‐ [email protected] Objectives: Migrating partial seizures of infancy (MPSI) is a severe, early onset epileptic encephalopathy characterised by frequent and intractable focal seizures and developmental delay. KCNT1 encodes a sodium activated potassium channel and is a recently described cause of MPSI.1 We evaluated our UK cohort of MPSI patients for mutations in KCNT1. Materials and Methods: Patients were recruited via a national surveillance study and detailed phenotyping was performed to delineate clinical, EEG, radiological and pathological features. A combined strategy of whole exome sequencing (Illumina paired-­‐end library preparation and sequencing on a Hi-­‐Seq platform) and direct Sanger sequencing was employed for molecular genetic investigation. For Sanger sequencing, the genomic KCNT1 DNA sequence was taken from Ensembl and primer pairs for all exons and flanking intronic regions were designed using primer3 software. Exons were amplified by PCR, sequenced by the BigDye terminator method and analysed with Chromas/Sequencher software. Results: Fourteen patients met the electroclinical criteria for a diagnosis of MPSI. Two different missense mutations were identified in 30% of patients tested. One mutation (c.2800G>A, p.A934T) was found in several patients and has been previously reported.1 Another mutation (c.811G>T, p.V271F) is a novel, previously unreported variant. These mutations are not seen in 1000 Genomes or other databases of genetic variation. Amino acid residues affected by these variants were highly conserved throughout species. Conclusions: KCNT1 is a significant disease-­‐causing gene in MPSI. However as we have demonstrated, this condition is genetically heterogeneous and further genetic aetiologies are yet to be discovered. Given the genetic heterogeneity of EIEE, the phenotypic spectrum of KCNT1 is likely to extend beyond this specific electroclinical syndrome. Reference 1. Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Nabbout R, et al. De novo gain-­‐of-­‐function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet 2012; 44: 1255-­‐9. O7 -­‐ 2139 Epilepsy and PCDH19 mutation: electrophysiological features Chemaly N, Kaminska A, Chiron C, An I, Pinard JM, Gauthier A, Arbues AS, Dulac O, Nabbout R. Neuropediatrics department, Centre de référence des épilepsies rares, Necker Enfants Malades Hospital, Paris, France -­‐ [email protected] PCDH19 mutations were first described in female patients affected with epilepsy with mental retardation. Clinical phenotype associated with PCDH19 mutations is considered to be a Dravet like syndrome. The aim of this study was to better characterize the electrophysiological characteristics of patients with positive PCDH19 mutation. 13 patients aged from 4 to 24 years at the time of the study with PCDH19 mutations were included. Longitudinal EEG videos were retrospectively reviewed (ictal and interictal). Interictal video EEGs recorded during cluster of seizure showed a slowed background activity for age in all patients, with focal slow waves and spike 18 waves, predominantly frontal or temporal in 11 patients. On the EEG recordings of 2 patients at 4 and 9 mouths, we registered periodic generalized discharges of slow waves and fast rhythmic activity without any clinical seizure. Interictal EEG recorded during seizure free periods showed normal or slightly slowed background activity in 7 patients, and the persistence in 6 patients of abnormalities which consisted of slowed activity in central regions (2/6), focal spikes (2/6), or generalized spike wave discharges (2/6). Ictal video EEG recorded showed in 3 patients frontal temporal initiation of seizure. One patient presented with atypical absences associated with myoclonus with generalized abnormalities on the EEG that were persistent during follow up. In patients with PCDH19 mutations, based on the clinical presentation, differential diagnosis includes i) Dravet syndrome because of fever sensitivity and frequent seizures events and ii) focal epilepsy due to the type of seizures. The combination of focal abnormalities with global alteration of the background activity on the EEG helps in the early identification of these patients, altogether with the clinical presentation, allowing an earlier molecular diagnosis. O8 -­‐ 2053 Epileptic spasms beyond infancy. Is LOES more than a description? Schoonjans A, Kenis S, Verhaert K, Van de Vel A, Ceulemans B. Antwerp University Hospital, Belgium -­‐ an-­‐[email protected] Objective Epileptic spasms (ES) are defined as clinical spasms associated with epileptic activity on the electroencephalogram (EEG). Although epileptic spasms are usually associated with West syndrome, they can also be seen in association with other epilepsy syndromes. Late-­‐onset epileptic spasms (LOES) are epileptic spasms starting after the first year of live. The aim of this study was to determine whether this condition represents a variant of the classic West syndrome, a precursor of the Lennox-­‐ Gastaut syndrome or a specific age related epileptic encephalopathy. Method We retrospectively reviewed the files of children who presented, between 1990 and 2012, with epileptic spasms after the age of 12 months. Results We report 10 patients (7 male / 3 female) with LOES followed at our pediatric neurology department. The mean age at onset of the epileptic spasms was 18.8 months (SD 5.0m). Four patients showed a normal development until the appearance of the ES. The etiology of those 4 patients was defined as cryptogenic. Interictal EEG showed hypsarrhythmia in 3/10 patients, modified hypsarrhythmia in 3/10 and focal epileptic activity in 2/10 patients. The ES were successfully treated in 7 patients after a mean duration of 9.9 months (SD 6.7m). Nevertheless only 3 out of those 7 patients persisted to be seizure free. The 3 patients for whom the ES could not be treated were cryptogenic and showed an evolution towards the Lennox-­‐Gastaut syndrome. Overall the outcome was poor with severe neurocognitive impairment in all except one patient. Conclusion LOES are epileptic spasms starting beyond infancy. We hypothesize that in children with a cryptogenic etiology LOES is an epileptic encephalopathy which positions itself between the West syndrome and the Lennox-­‐Gastaut syndrome. In children with a symptomatic etiology LOES is the expression of a secondary epileptic encephalopathy starting after the age of one year. O9 -­‐ 2019 Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2 Milh M, Boutry-­‐Kryza N, Sutera-­‐Sardo J, Mignot C, Auvin S, Villenueve N, Roubertie A, Héron B, Kaminska A, Altuzara C, Blanchard G, Ville D, Barthez H, Héron D, Afenjar A, Dorison N, Billette de Villeumeure T, Vercueil L, Perrier J, Lesca G, Villard L. Marseille, France -­‐ [email protected]­‐hm.fr BACKGROUND: Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development. Several genes have been associated with EOEE and a molecular diagnosis workup is challenging since similar phenotypes are associated with mutations in different genes and since mutations in one given gene can be associated with very different phenotypes. Recently, de novo mutations in KCNQ2, have been found mutated in about 10% of EOEE patients. Our objective was to confirm that KCNQ2 was an important gene to include in the diagnosis workup of EOEEs and to fully describe the clinical and EEG features of mutated patients. METHODS: We have screened KCNQ2 in a cohort of 71 patients with an EOEE. To be included in the cohort, patient’s epilepsy should begin before three months of age and be associated with abnormal interictal EEG and neurological impairment. Brain MRI should not show any structural abnormality. RESULTS: Out of those 71 patients, 16 had a de novo mutation in KCNQ2 (23%). Interestingly, in the majority of the cases, the initial epileptic features of these patients were comparable to those previously described in the case of benign familial neonatal convulsions (BFNS) also caused by KCNQ2 mutations. However, the interictal background EEG was altered and displayed multifocal spikes or a suppression-­‐burst pattern. The ongoing epilepsy and development were highly variable but overall severe: 15/16 had obvious cognitive impairment, half of the patients became seizure-­‐ free, 5/16 could walk before the age of 3 and only 2/16 patient acquired the ability to speak. CONCLUSION: This study confirms that KCNQ2 is frequently 19 mutated in neonatal onset epileptic encephalopathy. We show here that despite a relatively stereotyped beginning of the condition, the evolution is highly variable in terms of epilepsy and of cognitive evolution. O10 -­‐ 1986 Effective use of low dose of rufinamide after an initial worsening effect in Lennox-­‐Gastaut patients Corny J, Papon A, Bellavoine V, Storme T, Merdariu D, Ilea A, Bourdon O, Auvin S. Pediatric Neurology & Pharmacy Dpts, Robert Debré University Hospital, Paris, France -­‐ [email protected] Rufinamide is an new antiepileptic drug that has been approved for Lennox-­‐Gastaut syndrome (LGS). Rufinamide is usually initiates at 10mg/kg/day, followed by a titration of 10mg/kg/day every two days, until a maintenance dose of 45mg/kg/day. We conducted a retrospective study in the epilepsy unit of Robert-­‐Debré Children University Hospital, Paris, France. We identified 22 patients treated with rufinamide for at least three months (January 2010-­‐December 2012): n=10 LGS, n=6 infantile spasms and n=4 epileptic encephalopathy including tonic seizures. The patient with a decrease of 50% at least of the seizure frequency was defined as responder. Responder rate was 78.9% (19 patients). Our data showed that we did a slow titration (mean titration duration = 13.5 weeks). Initiation doses used were lower than the recommended dose (mean dose: 3.6 mg/kg/day). Regarding the responders, the mean maintenance dose was 10.5 mg/kg/day (3-­‐27 mg/kg/day): 7.9 mg/kg/day for LGS patients and 13.5 mg/kg/day for other epileptic syndromes. All responders had other concomitant AEDs, and 100% of responders had concomitant VPA treatment (mean dose = 26.4 mg/kg/day). During the titration, 10/15 patients were aggravated at the mean dose of 13.2 mg/kg/day (5-­‐25 mg/kg/day): 11.9 mg/kg/day for LGS patients and 16.5 mg/kg/day for other epileptic syndromes patients. No worsening of the seizure frequency was observed among the non-­‐responders group. All patients that experienced a worsening regain the positive effect on seizure frequency with the down titration. Rufinamide was effective in most of the patients. We observed an efficacy with a low dose of rufinamide. Surprisingly, 10/15 experienced an increase of seizure frequency during the up-­‐titration period after they have had a decrease of the seizure frequency. The efficacy of rufinamide was then observed with the use of a lower dose. Rufinamide was well tolerated. O11 -­‐ 1866 Successful use of Fenfluramine as add-­‐on treatment in Dravet syndrome: A two year prospective follow up Ceulemans B, Neels P, Boel M, Jorens P, Lagae L. Epilepsy Center for children and Youth, Pulderbos, Belgium -­‐ [email protected] Objective: Long term effect of of fenfluramine as an add-­‐on anti-­‐epileptic drug treatment in Dravet syndrome. Methods: In 2012 we published the results of 12 patients with Dravet syndrome treated with fenfluramine as add-­‐on anti-­‐epileptic drug. 7 were seizure free for at least 1 year. We now reviewed the results of the prospective follow up period (2011 and 2012) In this period, detailed seizure diaries were kept and cardiac evaluations were performed at least once a year. Results: Four out of 7 patients remained completely seizure free for the next 2 years. In the other 3 patients only rare seizures were observed. One patient had 3 tonic-­‐clonic seizures after tapering benzodiazepines in 2011 and 3 in a stress situation in 2012. One patient had one day of 4 tonic-­‐clonic seizures in 2011 and 3 in 2012. He is now 6 months seizure free after increase of sodium valproate. The third patient had only 2 fever induced tonic-­‐clonic seizures in 2011 and 1 in 2012. One patient had more than 75 % seizure frequency reduction in 2010. The seizure frequency further diminished and she had only 4 tonic-­‐clonic seizures in 2011 and 2 in 2012. From the two non-­‐responding patients one still remains non-­‐
responder and the other one became seizure free for the last 6 months of 2012. Two new patients were started on fenfluramine. Both had more than 75 % reduction with disappearance of status epilepticus and only sporadic tonic-­‐ clonic seizures. Seizure free periods were seen for 3 months in one child and 6 months in the other. We did not observe new cases of valvulopathy in this cohort. Conclusion: Also in this prospective follow up, the results of add-­‐on fenfluramine as anti-­‐ epileptic drug in Dravet syndrome are very promising. No new cardiac side effects were seen. O12 -­‐ 1838 CDKL5 mutations and antiepileptic drugs tolerability Magalhães C, Carrilho I, Ribeiro A, Chorão R, Santos M. Centro Hospitalar do Porto, Portugal -­‐ c-­‐[email protected] Objectives: The phenotype of CDKL5 (cyclin-­‐dependent kinase-­‐like 5) gene mutations includes early-­‐onset refractory epilepsy, severe psychomotor delay, autism and mild dysmorphic features. Our aim is to report our patients’ clinical features and its response to antiepileptic drugs. Material and Methods: From our database, we selected three patients with CDKL5 gene mutations, all from Northern Portugal. Results: We report three nonrelated girls aged eight, six and two years old. They all have severe developmental delay, autistic features 20 and hypotonia. Epilepsy started within the first six months of life, with several types of seizures including spasms. Two are still refractory to treatment, while the other one was difficult to control for a period of time, but then had few seizures. Initial electroencephalographic records were normal, evolving to multifocal epileptiform activity with burst suppression. In all the girls several antiepileptic drugs with different mechanisms of action were used. They all presented severe side effects related to the drugs, such as marked sedation, hypotonia, and aggravation of epileptic seizures, even with lower doses and independently of the drugs. Conclusions: CDKL5 gene is known to be involved in brain development, but most of its functions are still unclear, as is the relationship with MECP2 (methyl-­‐CpG-­‐ binding protein 2) gene. This disorder, previously known as atypical Rett syndrome, has its own characteristics, including epilepsy starting during the first year of life, severe motor and mental impairment and autism, with normal initial electroencephalograms evolving to severe epileptic encephalopathy patterns. The extreme sensibility to antiepileptic drugs, common to these patients, although not yet reported, may be an important feature of the disorder allowing earlier diagnosis. O13 -­‐ 1691 High dose (4 mg/kg/day) versus usual dose (2 mg/kg/day oral prednisolone in the treatment of infantile spasms: a randomized open trial Prabaharan C, Aneja S, Sharma S, Seth A. Lady Hardinge Medical College, New Delhi, India -­‐ [email protected] Objectives: Infantile spasms comprise a difficult-­‐to-­‐treat epileptic encephalopathy of young children. Effective treatment options include ACTH and vigabatrin, which are expensive in developing countries. Recent studies have shown good efficacy of high dose prednisolone. There are no studies comparing high versus usual dose prednisolone. Hence this study was planned to compare the efficacy and tolerability of high dose (4 mg/kg/day) versus usual dose (2mg/kg/day) oral prednisolone in the treatment of infantile spasms. Materials and methods: Children aged 3 months to 2 years with infantile spasms and EEG evidence of hypsarrhythmia or its variants were randomized to receive either high dose (4mg/kg/day) or usual (2 mg/kg/day) dose predisolone. Children with active tuberculosis and severe acute malnutrition were excluded. The primary outcome was cessation of spasm for atleast 48 hours on day 14. The proportion of adverse effects in both the groups was also compared (Clinicaltrials.gov identifier NCT01575639). Results: Out of 63 children enrolled, 31 were in the high dose group, and 32 in the usual dose group. Spasm cessation at day 14 was significantly higher in the high dose group as compared to the usual dose group [16/31 (51.6%) versus 8/32 (25%), p=0.03]. The proportion of adverse effects such as weight gain, hypertension, irritability, and infections were comparable in both the groups. None of the patients required discontinuation of treatment for adverse effects. Conclusion: High dose prednisolone was found to be more efficacious in the treatment of infantile spasms as compared to usual dose prednisolone with a comparable safety profile. Parallel session 3: Mitochondrial disorders Chairs: Linda De Meirleir and Ingrid Tein O14 -­‐ 1917 Hypomyelination with brain stem and spinal cord involvement and severe leg spasticity (HBSL): Mutations in DARS are responsible Wolf NI, van der Knaap MS, de Coo IFM, Vanderver A, Leventer RJ, Damiani S, Simons C, Juneja M, Verma IC, Prabhakar P, Blaser S, Raiman J, Abbink TEM, Taft R. Dept. of Child Neurology, VU University Medical Center, Amsterdam -­‐ [email protected] Objective: To improve diagnosis in children with hypomyelination. Patients and Methods: Four patients were identified with a novel hypomyelinating disorder using MRI pattern recognition. Whole exome sequencing (WES) was performed in two children and one parent. One additional patient with a comparable different MRI pattern underwent WES in an independent project. Results: MRI showed a homogeneous mildly increased T2 signal of the supratentorial white matter consistent with hypomyelination and in addition hyperintense T2 signal of the anterior brain stem, the superior and inferior cerebellar peduncles and the dorsal columns of the spinal cord over its entire extent. WES revealed homozygous and heterozygous missense mutations in DARS, coding for the cytoplasmic aspartyl tRNA synthetase. Five more patients with a similar MRI pattern were identified subsequently, all with mutations in DARS. One mutation, c.766A>C, was found in three unrelated families from India and Pakistan. Clinical symptoms started in the first year of life and included nystagmus and leg spasticity. Cognition was mildly impaired in the younger children. Two developed epilepsy. We called this disorder HBSL (hypomyelination with brain stem and spinal cord involvement and severe leg spasticity) to underline the MRI 21 similarities with LBSL (leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate) which is caused by mutations in DARS2, the mitochondrial counterpart of DARS. Conclusions: MRI pattern recognition is possible also in hypomyelinating disorders and allows identification of novel disorders. WES is able to pinpoint the genetic defect also in small groups of single patients. Mutations in DARS cause a hypomyelinating white matter disorder, HBSL, with characteristic MRI changes. O15 -­‐ 2036 Early onset mitochondrial encephalomyopathy with pulmonary hypertension due to [Fe-­‐S] cluster deficiency Abela L, Rohrbach M, Häberle J, Mayr H, Ahting U, Nuoffer JM, Scheer I, Bauer A, Hug M, Klauwer D, Plecko B Department of Child Neurology, Childrens Hospital, University of Zürich -­‐ [email protected] Introduction: Recently iron cluster [Fe-­‐S]-­‐synthesis defects have been recognized as one possible cause of combined respiratory chain defects. The [Fe-­‐S]-­‐cluster is needed for synthesis of lipoic acid, which serves as a cofactor in all respiratory chain complexes. Patient: we here describe a 33 GW preterm female infant of non-­‐ consanguineous parents with BW, BL and HC within 50th-­‐75th PC. Neonatal feeding problems and recurrent bradycardia and apnea necessitated 4 weeks of hospitalization. She developed visual contact and social smile by 8 weeks of age. At age 10 weeks failure to thrive and severe apnea lead to readmission. Cardiac ultrasound revealed severe pulmonary hypertension. Cranial MRI showed diffuse leukodystrophic supra-­‐and infratentorial changes with diffusion restriction on T2 weightes images. Plasma and CSF lactate were markedly increased and glycine levels in plasma and CSF were moderately increased. Biochemical analysis of a fresh muscle biopsy showed a combined defect in complex I, II and III; PDHC activity was not measured due to limited sample size. Reduction of lipoic acid could be assessed by Western Blot analysis in a peripheral blood smear. Immediate treatment with thiamine, riboflavine, coenzyme Q10, sodium benzoate and L-­‐carnitine could not alter the rapidly progressive course with respiratory insufficiency, severe muscular hypotonia, recurrent seizures and death at age 3.5 months. Molecular analysis of the NFU1 gene revealed one novel splice site mutation in exon 6. Analysis of cDNA for identification of the second allele is pending. Conclusions: Defects of [Fe-­‐S]-­‐cluster synthesis can be suspected by elevated lactate and glycine in plasma. NFU1 deficiency seems to produce a distinct and recognizable phenotype with associated primary pulmonary hypertension and a short window of opportunity for therapeutic interventions. Preliminary data on poor mitochondrial uptake of orally administered lipoic acid warrant further studies. O16 -­‐ 1908 A homozygous mutation in IB57 involved in intramitochondrial iron-­‐sulfur cluster synthesis causes severe encephalopathy and mypathy in two neonates Vanlander A, Wilbrecht C, Ajit Bolar N, Smet J, De Paepe B, De Latter E, Van Laer L, Loeys B, Lill R, Van Coster R Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Gent, Belgium -­‐ [email protected] Background: Combined OXPHOS deficiencies involving complexes I and II have recently been detected in patients with deficient iron-­‐sulfur cluster (ISC) biogenesis. So far, patients were reported with pathogenic mutations in NFU1 and BOLA3 presenting with severe encephalomyopathy at young age. Objective: Two siblings with combined deficiency of complex I and II were investigated for possible defect in ISC. Patients and Methods: The siblings presented soon after birth with severe encephalomyopathy and died in the neonatal period. Biochemical investigations showed increased lactate in serum and increased glycine in CSF. Considering the consanguineous descent a search for genes in homozygous regions related to ISC metabolism was performed. Results: Isolating IBA57 as a strong candidate gene, sequencing detected a homozygous mutation (c.941A>C) in the two siblings and a heterozygous carrier status in both parents. Western blotting showed a severe decrease of CRM for the IBA57 protein. The protein amount in the complexes I and II was significantly decreased. Transfection experiments in HeLa cells demonstrated that the mutation was pathogenic and that excessive degradation of the IBA57 protein was responsible for the defective ISC biosynthesis. Conclusion: This is the first report of a pathogenic mutation in IBA57 in human. O17 -­‐ 1786 Exome Sequencing Reveals Heterozygous Mutations in the ADCK3 Gene in Siblings with Cerebellar Atrophy but Extreme Phenotypic Variability Blumkin L, Silver-­‐Leshinsky E, Zerem A, Yosovich K, Jalas C, Lev D, Lerman-­‐Sagie T. Metabolic Neurogenetic Service, Pediatric Neurology Unit, Wolfson Medical Center, Holon, Sackler School of Medicine, Tel-­‐Aviv University, Tel-­‐Aviv, Israel -­‐ [email protected] 22 Objectives: Primary CoQ10 deficiency is a rare, autosomal recessive, clinically heterogeneous disorder caused by defects in proteins involved in the coenzyme Q synthesis pathway and presents with five major phenotypes. Mutations in the ADCK3 gene have been associated with the ataxic form of CoQ10 deficiency. We describe a highly variable clinical presentation of cerebellar ataxia in two sisters with ADCK3 gene mutation. Materials and methods: The younger sister demonstrates early onset rapidly progressive cerebellar ataxia accompanied by motor and non-­‐motor cerebellar features, as well as cognitive decline and psychiatric problems. Mitochondrial respiratory chain enzyme analysis in muscle showed a decrease in complex I+III. Progressive cerebellar atrophy was demonstrated on serial brain MR imaging. Coenzyme Q10 supplementation, started at the age of 5 years led to a significant improvement in motor and cognitive abilities with partial amelioration of the cerebellar signs. Discontinuation of this treatment resulted in worsening of the ataxia, cognitive decline and severe depression, associated with a significant progression of the cerebellar atrophy. The older sister, who is 32 years old, has non progressive dysarthria and clumsiness from the age of 10 years and MRI reveals cerebellar atrophy. Results: Exome sequencing identified compound heterozygosity for a known (Th582del) and a novel (P602R) mutation in the ACDK3 gene. Conclusion: Patients with primary CoQ10 deficiency due to ADCK3 mutations can demonstrate a wide spectrum of clinical presentations even in the same family. It is difficult to diagnose CoQ deficiency based solely on the clinical presentation. Exome sequencing can provide the molecular diagnosis but since it is expensive and not readily available, we recommend a trial of CoQ treatment in patients with ataxia and cerebellar atrophy even before confirmation of the molecular diagnosis. O18 -­‐ 1777 Thiamine transporter-­‐2 deficiency: a reversible cause of encephalopathy in children. Pérez-­‐Dueñas B, Ortigoza JD, Serrano M, Fons C, Muchart J, Rebollo M, Molero M, Casado M, Artuch R. Department of Child Neurology, Sant Joan de Déu Hospital, University of Barcelona, Spain, and CIBER-­‐ER, ISCIII, Spain -­‐ [email protected] Background: SLC19A3 mutations cause thiamine transporter–2 deficiency, a recently recognized cause of reversible encephalopathy. Thiamine is an essential cofactor of 3 mitochondrial enzymes involved in pyruvate oxidation and brain energy production. Aims: To establish clinical-­‐biochemical-­‐radiological criteria for early diagnosis and treatment of SLC19A3 defects. Patients and Methods: Two siblings presented with recurrent episodes of encephalopathy between 5 and 17 years, associating dystonia, cranial nerve palsy, seizures, and T2-­‐
signal abnormalities within the cerebral cortex, basal ganglia and thalami. Thiamine administration reversed these abnormalities in a few days and the children remained asymptomatic after a three-­‐year follow-­‐up. A 30-­‐
day-­‐old infant presented with lactic acidosis, lethargy, opisthotonus and brain lesions affecting the perirolandic cortex, putamina and medial thalami. 48 hours after thiamine administration irritability, feeding difficulties and opisthotonus disappeared and the patient recovered consciousness. Biochemical analysis was normal in both siblings but detected lactic acidosis and high excretion of alpha-­‐ketoglutarate in urine in the infant with Leigh encephalopathy; these findings normalized after thiamine administration. SLC19A3 mutation analysis revealed the following mutations in combined heterozygosis (c.74dupT, c.980-­‐14A>G) and in homozygosis (c.68G>T). Results: Based on our experience and on the literature review, the following diagnosis criteria were established: a) Episodes of acute encephalopathy presenting with seizures, dystonia, ataxia or brain stem dysfunction; b) Symmetric involvement of the striatum, medial thalami, brain cortex and infra-­‐ tentorial structures (tegmental part of the midbrain, pons, cerebellar white matter or dentate nuclei); c) Lactic acidosis and alpha-­‐ketoglutarate excretion during infancy; d) Rapid clinical and radiological improvement after thiamine supplementation. Conclusions: Thiamine-­‐transporter 2 deficiency causes acute encephalopathy and mitochondrial dysfunction in children. Early recognition after clinical-­‐ radiological-­‐biochemical criteria allows reversing the phenotype with thiamine administration and also differentiating this entity from other causes of acute encephalopathy in children (i.e. hypoxia, mitochondrial encephalopathy, nutritional Wernicke, rhomboencephalitis). O19 -­‐ 1664 Succinyl-­‐CoA ligase deficiency: report on the first patient resulting from a combined defect in SUCLG1 and SUCLG2 genes Zafeiriou DI, Batzios S, Vargiami E, Willemsen M, Morava E, van den Heuvel L, Smet J, Van Coster R, Seneca S, Wanders R, Waterham H, Wevers R. 1st Department of Pediatrics, Aristotle University of Thessaloniki, Greece -­‐ [email protected] Succinyl-­‐CoA ligase (SUCL) deficiency represents an encephalomyopathic form of mitochondrial DNA depletion syndromes. This mitochondrial matrix protein consists of an a subunit, encoded by SUCLG1 gene, and a b subunit encoded by either SUCLA2 or SUCLG2 genes. So far, mutations in SUCLA2 and SUCLG1 have been reported in literature. We describe the fatal clinical course of an 8 month-­‐old girl with a combined defect in SUCLG1 and 23 SUCLG2. Since the first months of her life the patient demonstrated retardation of gross motor development and generalized hypotonia. Elevated methylmalonic and 3-­‐hydroxyisovaleric acid in urine, in combination with an increase in 3-­‐hydroxyisovalerylcarnitine in plasma acylcarnitine analysis was found. Neuroimaging at this point revealed enlarged subarachnoidal spaces and symmetric T2-­‐ hyperintense lesions of the basal ganglia. The patient developed progressively severe myopathy with pronounced muscle weakness and dystonia. Brain MRI at 26 months of age demonstrated deterioration with bilateral increased attenuation of putamen and caudate nuclei, severe brain atrophy and ventriculomegaly. Lactate increase was present throughout the patients’ clinical course. Brainstem auditory evoked potentials revealed sensorineural hearing impairment. The constellation of the above findings prompted a diagnostic workup for SUCL deficiency. Muscle respiratory-­‐chain enzyme activity analysis showed complex I deficiency while the quantitation of mtDNA content demonstrated moderate depletion. Direct sequencing analysis of SUCLA2 and SUCLG1 revealed a heterozygous mutation in SUCLG1 gene. Further sequencing of the SUCLG2 gene led to the identification of a second mutation. Enzymatic activity analysis in fibroblasts showed decreased SUCL activity leading to the hypothesis that the described mutations result in disruption of the assembly of the different subunits of the enzyme. Our data extend the knowledge on the genetic defects causing SUCL deficiency. We suggest that SUCLG2 sequencing should take place in the case where only one disease causing mutation in either SUCLG1 or SUCLA2 is found. O20 -­‐ 1660 Leigh syndrome: a multicenter study of natural history Sofou K, de Coo IF, de Angst IB, Isohanni P, Pihko H, Östergaard E, Naess K, De Meirleir L, Tzoulis C, Uusimaa J, Mankinen K, Bindoff LA, Tulinius M, Darin N. Mitochondrial Clinical and Research Network (MCRN), Sweden -­‐ [email protected] Background: Leigh syndrome (LS) is an early-­‐onset, progressive neurodegenerative disorder, associated with defects involving mitochondrial oxidative phosphorylation. It is the most common distinct mitochondrial disease phenotype in children. Objectives: To study the phenotypic and genotypic spectrum of patients with LS, characterise the clinical course and identify predictors of survival in a large cohort of patients. Materials and methods: A retrospective study of patients with LS followed at eight European centres specialising in mitochondrial diseases: Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. An electronic database was developed for data collection. All centres obtained ethical approval for the conduction of this study. Results: A total of 130 patients with LS were included, 77 with identified pathogenic mutations. Median age at onset of symptoms was 7 months. Seventy-­‐four patients experienced acute exacerbations and/or relapses requiring hospitalisation, of whom 40% necessitated intensive care. Fifty-­‐one patients (39%) died at a median age of 2.4 years. The presence of pathological signs at birth and history of seizures were associated with significantly higher occurrence of acute exacerbations/relapses. Clinical onset ≤ 6 months of age, history of failure to thrive, admission to intensive care unit and brainstem dysfunction on neuroimaging, were significantly related to poor survival. Among patients with identified pathogenic mutations, those with m.8893T>G, SURF1 and SLC19A3 mutations were found to have poorer survival and more widespread lesions on neuroimaging, compared with patients having other pathogenic mutations. Conclusions: To our knowledge, this is the first study performed in a large cohort of patients to describe the natural history of LS and to identify genotype-­‐ phenotype correlations and predictors of survival. O21 -­‐ 1552 Biotin-­‐responsive basal ganglia disease revisited: Clinical, radiologic, and genetic findings Tabarki Melaiki B, Al Hashem A, Al Shafi S, Al Shahwan S, Zuccoli G. Department of Pediatrics, PSMMC, Riyadh, Saudi Arabia -­‐ [email protected] Background Biotin responsive basal ganglia disease is a treatable neurometabolic condition resulting from mutations in the SLC19A3 gene. Objective: To investigate the clinical, genetic, and neuroradiologic data of BBGD and clarify the disease spectrum. Methods: We investigated all patients attending our Division of Pediatric Neurology with a genetically proven diagnosis of BBGD between 2009 and 2012. All patients underwent a detailed medical history and clinical examination, extensive laboratory investigations including genetic tests, and brain MRI. Finally, we conducted a systematic review of the literature. Rresults We enrolled 15 patients meeting the diagnostic criteria for BBGD, and analyzed the data on 16 patients from 5 previous reports. The BBGD occurred predominantly in preschool/school-­‐aged patients in the Saudi population, but it was also observed in other ethnic groups. The typical clinical picture consisted of recurrent subacute encephalopathy leading to coma, seizures, and extrapyramidal manifestations. The brain MRI typically showed symmetric and bilateral lesions in the caudate nucleus and putamen, infra-­‐ and supratentorial brain cortex, and in the brainstem. Vasogenic edema characterized the acute crises as demonstrated by DWI/ADC. Atrophy and gliosis in the affected regions were 24 observed in patients with chronic disease. Early treatment with a combination of biotin and thiamine resulted in clinical and neuroradiologic improvement. Death and neurologic sequelae including dystonia, mental retardation, and epilepsy were observed in those who were not treated or were treated late. Conclusions BBGD is an underdiagnosed pan-­‐ethnic treatable condition. Clinicians caring for patients with unexplained encephalopathy and neuroimaging showing vasogenic edema in the bilateral putamen and caudate nuclei, infra-­‐ and supratentorial cortex, and brainstem should consider this disorder early in the hospital course because a therapeutic trial with biotin and thiamine can be lifesaving. Our study also provide new insights into the disease:1/the neuroimaging features,2/the pathogenesis, and 3/the treatment as thiamine is main treatment. O22 -­‐ 1585 New insights into the spectrum of phenotypes and genotypes in Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) Hamilton EM, van Berge L, Steenweg ME, Linnankivi T, Uziel G, Krägeloh-­‐Mann I, Brautaset NJ, Andrews I, de Coo IF, van Berkel CG, Polder E, Scheper GC VUMC Amsterdam, The Netherlands -­‐ [email protected] Objectives: Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) is a rare autosomal recessive disorder with a distinctive MRI and spectroscopy pattern, clinically characterized by slowly progressive ataxia, spasticity and dorsal column dysfunction. Patients have mutations in the DARS2 gene. Recent observations indicate that the clinical variety of the disease is much wider than initially thought. The aim of this study was to make an inventory of the clinical characteristics and genotypes in LBSL patients and to explore a possible genotype-­‐phenotype correlation. Materials and Methods: A cross-­‐sectional observational study was performed in 78 patients with two DARS2 mutations. Clinical information was collected via questionnaires and an inventory was made of the DARS2 mutations in our patients as well as those previously published. Results: Medical information was obtained on 66 patients. The clinical severity varied from neonatal onset, rapidly fatal disease to an adult onset disorder with a slow and mild course. The most common phenotype was characterized by childhood onset and gradual neurological deterioration. In total, 60 different DARS2 mutations have been identified (13 novel). Except for four published cases, all patients were compound heterozygous. The groups of patients sharing the same two mutations were very small, precluding a formal genotype-­‐phenotype correlation. However, some combinations of mutations were consistently associated with a benign phenotype. Conclusions: This study describes the natural course and genotype in the largest cohort of LBSL patients to date. There is a wide variability in clinical severity, and patients have numerous different mutations. In most cases, the disease has a relatively slow and mild course, but in some cases the disease has an early-­‐ infantile onset and leads to death within 2 years. The available evidence suggests that the genotype influences the phenotype, but larger numbers of patients are necessary to confirm this. Parallel session 5: Immunology and infectious diseases Chairs: Banu Anlar and Nina Barisic O23 -­‐ 1732 Childhood relapsing immune-­‐mediated polyneuropathy and hemolysis is associated with CD59 deficiency Nevo Y, Ben Zeev B, Tabib A, Straussberg R, Anikster Y, Shorer Z, Fattal-­‐Valeski A, Ta Shma A, Aharoni S, Rabie M, Zenvirt S, Goldshmidt H, Fellig Y, Shaag A, Mevorach D, Elpeleg O. Hadassah, Hebrew Univerisity Medical Center, Jerusalem -­‐ [email protected] The objective of the present study was to elucidate the molecular basis of a new clinical entity of childhood familial immune mediated relapsing polyneuropathy associated with chronic Coombs-­‐negative hemolysis. Since infancy these children had recurrent episodes of weakness and hemolysis with partial improvement following immune modulating therapy. One child died at the age of 3.5 years while the others demonstrated severe lower limb paralysis. Methods: A founder mutation was searched for using homozygosity mapping followed by exome sequencing in 5 infants of North-­‐African Jewish origin from 4 unrelated families. The expression of CD59, CD55, and CD14 was examined in blood cells by flow cytometry followed by Western blot of the CD59 protein. Results: homozygous missense mutation, p.Cys89Tyr in CD59, was identified in all patients. The mutation segregated with the disease in the families and had a carrier rate of 1:66 among Jewish subjects of North-­‐African origin. The mutated protein was present in the patients' cells in reduced amounts and was undetectable on the membrane surface. Discussion and conclusion: CD59 deficiency is a common finding in RBCs and WBCs in patients with chronic hemolysis suffering from paroxysmal nocturnal hemoglobinuria in which the acquired mutation in the PIGA gene leads to membrane loss of glycosylphosphatidylinositol-­‐anchored membrane proteins, including CD59. Based on the results of the present study, we suggest that the Cys89Tyr mutation in CD59 is associated 25 with a failure of proper localization of the CD59 protein in the cell surface and decreased complement inhibition. This mutation is manifested clinically in infancy by relapsing peripheral demyelinating disease and chronic hemolysis. O24 -­‐ 1725 Autonomic dysfunction in children with Guillain-­‐Barré syndrome Aziz M, Watson L, Plant N, Vassallo G. Department of paediatric neurology, Royal Manchester children’s hospital, Oxford road, Manchester, UK -­‐ [email protected] Background: Guillain-­‐Barré syndrome (GBS) is an autoimmune disorder causing motor, sensory and autonomic dysfunction. Autonomic disturbance involvements are of sweating, heart rate and rhythm, blood pressure, ileus and sphincter control. The primary aim of this study is to describe the incidence, severity and management of autonomic dysfunction and their relationship with clinical, CSF and neurophysiological features in a cohort of patients with GBS. Methods: A 10-­‐year retrospective review of cases identified using the international classification of disease (ICD) code for GBS in a tertiary paediatric centre. Results: Twenty-­‐seven patients were included in this study. Patients were aged 5.7 years (IQR 3.5-­‐8.4 years) and 18 (18/27; 67%) were male. Autonomic dysfunction was seen in fourteen patients (52%). The length of hospital stay was 32.5 (15.5 -­‐ 53.5) days. Hypertension was the most observed autonomic dysfunction, seen in twelve patients (44%), tachycardia in four patients (14%) and bradycardia in one child (3%). The ECG were normal. There was no incidence of altered temperature, sweating and ileus. The duration of hypertension was 11 (7.3 -­‐ 26) days and correlated with the length of hospital stay (Rho=0.65; p=0.021). Hypertension occurred 9 to 15 days from symptom onset and within 24 to 48 hours of maximum motor disability. Nine hypertensive patients required treatment; six were controlled with a single agent. Patients with more extensive motor disturbance (i.e four limb involvement) required more anti-­‐ hypertensive medications (Upper limb Rho=-­‐0.709; p=0.033, lower limb Rho=-­‐0.72; p=0.029). Hypertension resolved in all patients prior to discharge and was not related to grade of muscle weakness, CSF protein levels, IVIg therapy, severity of nerve conduction or subtype of GBS (AIDP, AMAN, AMSAN, and Miller fisher variant). Conclusion: Dysautonomia, mainly hypertension occurs early in the disease course when patients are at their clinical nadir and resolves before limb paralysis starts to improve. O25 -­‐ 2018 Risks of Relapse and Severe Outcome in Children with a Clinically Isolated Acute Transverse Myelitis at Onset: a French-­‐British collaborative study Deiva K, Absoud M, Niotalkis G, Hemingway C, Lim M, Tardieu M. Department of Pediatric Neurology, National Referral Centre for Neuro-­‐Inflammatory Diseases in Children, Hôpitaux Universitaires Paris-­‐Sud, Le Kremlin Bicêtre -­‐ [email protected] Objective: To determine risk factors of relapse and severe outcome in children with isolated acute transverse myelitis (IATM) at onset. Methods: In this retrospective study, clinical and MRI datas of 95 children less than 16 years old with IATM followed in France and United Kingdom were gathered from 2004 to 2011. Clinical outcome at the last follow-­‐up was assessed using the ASIA impairement scale and by Kutzke Disability score (DSS) and a severe outcome was defined when ASIA impairment scale was < D and/or DSS score ≥ 4. Results: Median age was 9 years (0.7-­‐16) with a mean follow-­‐up of 1.8±1.7 years. Sixteen (17%) were diagnosed with a relapsing disease (multiple sclerosis in 14 and neuromyelitis optica in 2). Children with relapse tend to be significantly younger than children with a monophasic evolution (8 years (4-­‐15) vs 10 years (0.7-­‐16), p=0.03) and they frequently had a nadir of symptoms ≥ 24H (4 vs 49, p=0.005). Presence of brain MRI lesions at onset was more frequent in children who had a relapse (8/10 vs 20/62, p=0.01). Twenty-­‐eight (30%) children had a severe outcome and was frequently observed in children who had a time to nadir of symptoms ≤ 24H and with sphincter dysfunctions (p=0.02 and p=0.01) while pleiocytosis ≥ 10/mm3 was frequently present in children with non severe outcome (7 vs 32, p=0.01). On MRI studies, gadolinium enhancement was significantly present in children with severe outcome (20/24 vs 16/48, p=0.0001) Conclusion: In this largest study of IATM in children, we have identified that age, time to nadir ≥24H and presence of lesions on brain MRI were associated with relapse while time to nadir of symptoms ≤ 24H, sphincter dysfunction, absence of pleiocytosis and presence of gadolinium enhancement on brain MRI seems to be risk factors for severe outcome. O26 -­‐ 1915 Immunological studies in Rapid-­‐onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome Biancheri R, Napoli F, Calcagno A, Ceccherini I, Hacohen Y, Jacobson L, Lang B, Vincent A, Maghnie M. Child Neurology and Psychiatry Unit, Department of Neuroscience, Istituto Giannina Gaslini, Genova, Italy -­‐ [email protected] 26 Objectives: To evaluate a possible role of autoimmunity in rapid-­‐onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) syndrome. This disorder affects previously normal children at 2 to 4 years of age. In spite of a high suspicion for genetic etiology, disease-­‐associated genetic variations have not been identified as yet. On the other hand, a paraneoplastic/autoimmune etiology has been suggested mainly because of the association with neural crest tumors. Materials and methods: Six patients with ROHHAD underwent clinical, neurophysiological and neuroradiologic studies; serum antibodies to neuronal antigens (NMDAR, LGI1, CASPR2, dopamine receptor, AMPAR, Ganglionic AChR (autonomic), VGKC and VGCC), often found in association with tumours, were assessed. Results: All patients (2M, 4F) had normal birth size and no symptoms until 2-­‐4 years, when they developed rapid weight gain (mean BMI Z-­‐score +3.5SDS), hyperprolactinemia, water/salt balance disruption and behavioral problems or EEG alterations (4 patients). Central apnoeas were diagnosed at age 2-­‐6.5 in 4 patients and non-­‐invasive ventilation was started. Central adrenal insufficiency was found in 2 patients. 4 patients had growth hormone deficiency, 2 had central precocious puberty and 5 had central hypothyroidism. Brain MRI was normal or not significant in all patients. A retroperitoneal mass was found in 3 patients. None of their sera were positive for any of the neuronal antibodies tested. Conclusions: The possible autoimmune etiology of ROHHAD is based on the frequent association with neural crest tumors, the extensive infiltrates of lymphocytes and histiocytes in the hypothalamus of some patients, and a partial response to intravenous immunoglobulin, rituximab and cyclophosphamide. We investigated the sera for most of the known autoantibodies associated with different forms of immune-­‐mediated encephalitis, but all results were negative. Additional studies to look for novel autoantibodies are needed. O27 -­‐ 2082 Anti-­‐myelin oligodendrocyte glycoprotein antibody positivity in children with demyelinating episodes Hughes SE, James S, Flynn P, Smyth G, McKinstry S, Rennie I, Hanrahan D, Peake D, Tirupathi S. Department of Neurology, Royal Belfast Hospital for Sick Children, Belfast, UK. -­‐ [email protected] Objectives: Anti-­‐myelin oligodendrocyte glycoprotein (anti-­‐MOG) antibodies have been identified in paediatric cases of demyelinating disease. Their relevance remains uncertain but MOG-­‐positive acute disseminated encephalomyelitis (ADEM) may indicate a more pronounced systemic onset of symptoms and signify higher recurrence risk. We aimed to define the features of antibody-­‐positive cases in our paediatric population. Materials and Methods: Case series of paediatric patients with monophasic or recurrent demyelinating episodes who demonstrated anti-­‐MOG antibodies in serum. Results: We describe four children; three females, one male. All cases were serum anti-­‐MOG antibody positive and aquaporin-­‐4 antibody negative. Mean follow-­‐up was 9.8 months (range 1-­‐30 months). Mean age at onset was 6 years (range 5-­‐7 years). All presented with ADEM which was monophasic in three cases. In the fourth, unilateral optic neuritis (ON) developed 8 weeks later and subsequently reocurred after three months. Cranial Magnetic Resonance Imaging (MRI) was typical for ADEM in all, although initial scans were normal in three cases. Two cases had spinal cord lesions, one with widespread high T2-­‐signal. All had cerebrospinal fluid (CSF) pleocytosis, with marked lymphocytosis in two, and one had markedly elevated CSF protein. CSF oligoclonal bands were absent in the three cases in which it was studied. Each received intravenous steroids at diagnosis of ADEM, followed by reducing doses of oral corticosteroid; this was also administered for each episode of ON in the polyphasic case. There was a good recovery in all cases. Conclusions: In this case series, anti-­‐MOG antibody positivity was associated with monophasic ADEM in all but one case, which also had recurrent optic neuritis. All had a full recovery, suggesting that the antibody does not necessarily confer a poor short-­‐term prognosis. Although anti-­‐MOG antibody is a useful marker for autoimmune aetiology, it remains to be seen if it predicts recurrence or multiple sclerosis in the longer term. O28 -­‐ 1989 Children in England with narcolepsy during the H1N1 (swine ‘flu) pandemic: clinical features in those receiving AS03 adjuvanted pandemic A/H1N1 (2009) influenza vaccine and in unvaccinated cases Winstone AM, Stellitano L, Verity CM, Shneerson JM, Andrews N, Stowe J, Miller E. Addenbrookes Hospital Cambridge UK -­‐ [email protected] Objectives. To retrospectively identify cases of narcolepsy aged 4 to 18 years in England with onset from January 2008 and investigate differences in clinical features between vaccinated and unvaccinated cases. Materials and Methods. Cases of narcolepsy aged 4 to 18 years with onset from January 2008 were identified by sleep centres and by paediatric neurologists in 16 English hospitals. Clinical information and sleep test results extracted from centre notes were reviewed by an expert panel. General practitioners provided vaccination and clinical histories. Results. Case notes for 245 children were reviewed; 75 had narcolepsy. Eleven were vaccinated before onset of symptoms. All 75 children presented with excessive daytime sleepiness. Presenting symptoms more frequently reported in the vaccinated cases were cataplexy, weight gain, behavioural problems, complex movement 27 disorders, tongue protrusion and slurred speech. Other presenting symptoms were sleep-­‐disturbance/ nightmares, facial hypotonia, hypnagogic hallucinations, snoring, sleep paralysis, prolonged night time sleep, restless/painful legs, ptosis, ataxia, sleep automatisms and incontinence. Eventually all the vaccinated cases developed cataplexy compared to 38/64 (59%) of the unvaccinated cases. Investigations were as follows. Human leukocyte antigen (HLA) DQB1*0602 typing was performed in 6 vaccinated cases, all were positive. In 28 non-­‐
vaccinated cases HLA typing was done and 25 were positive. Cerebrospinal fluid orexin levels were measured in 2 vaccinated cases (both low) and 11 unvaccinated (9 low, 2 normal). Multiple sleep latency studies were performed in 9 vaccinated cases (all abnormal); they were performed in 56 unvaccinated cases (46 abnormal). Conclusions. We previously reported an increased risk of narcolepsy after A/H1N1 (2009) influenza vaccine. We have now analysed the clinical features of the cases. Some presenting symptoms were more frequently recorded in vaccinated cases who all developed cataplexy within the study period. Long term studies are needed to detect any differences in eventual outcome between vaccinated and unvaccinated cases. O29 -­‐ 1951 Childhood encephalitis: epidemiological, clinical and radiological characteristics and their impact on the outcome Liptai Z, Ujhelyi E, Mihaly I, Barsi P, Szent Laszlo Hospital, Dept. of Paediatrics, Budapest, Hungary -­‐ [email protected] Aim of the study: to estimate the frequency, etiologies and characteristics of childhood encephalitis and their impact on the outcome. Patients and methods: data of paediatric patients treated for encephalitis between 1998 and 2009 at Szent László Hospital were statistically analysed. Results: In the 12-­‐year-­‐period 178 children were treated for 179 episodes. 85% had infectious encephalitis (IE), 13% had acute disseminated encephalomyelitis (ADEM). The infectious agent was verified in 2/3 of cases. The commonest were herpes simplex virus (HSV): 16%, enterovirus: 38%, varicella-­‐zoster virus (VZV): 11%. Prodromal illness was present in 65%. Focal deficits, confusion and severe disturbance of consciousness were more common in ADEM than in IE. Seizures occurred more often in HSV encephalitis. Focal deficits were more typical of VZV. CSF was abnormal in 85, EEG in 93%. Severe diffuse dysfunction occurred more often in ADEM than in IE. Periodic changes, focal and paroxysmal changes were more typical of HSV than of other etiologies. MRI was abnormal in 96% of ADEM and 53% of IE cases examined. 58% of all and 79% of ADEM patients required intensive care. HSV patients were more likely to require intensive care and for a longer duration, than patients with other etiologies. Mortality rate was 3%. Sequelae (26%) occurred more often after ADEM, following severely disturbed consciousness, seizure(s), severe diffuse dysfunction, focal, paroxysmal and periodic changes of the EEG and abnormal MRI. 14% developed epilepsy. Relapses occurred in 1 HSV and 2 ADEM patients. The most important predictors of unfavourable outcome were: ADEM, HSV-­‐etiology, severely disturbed consciousness, focal seizures, paresis, pyramidal signs, paroxysmal EEG changes, cortical, subcortical abnormal signal on MRI. Conclusion: This large series of paediatric encephalitis patients is unique in terms of the high-­‐ratio of successful epidemiological workup and of the correlations found between the acute phase and the outcome. O30 -­‐ 1893 Guillain-­‐Barré syndrome in UK children: H1N1 vaccinations, preceding infections and clinical features Verity C, Addenbrookes Hospital, Cambridge, UK -­‐ [email protected] Objectives. To identify all new cases of Guillain-­‐Barré syndrome (GBS) or Fisher syndrome (FS) in United Kingdom (UK) children in the 2 years following September 2009 and determine the proportion that was temporally associated with recent infections, with pandemic H1N1 (2009) strain influenza vaccination or with seasonal influenza vaccination. To report the clinical features of these cases. Materials and Methods. A prospective UK-­‐
wide epidemiological study using the British Paediatric Surveillance Unit (BPSU) system, including all children aged ≤16 years meeting the Brighton Collaboration criteria for GBS or FS. Results. We identified 112 children with GBS (66 boys and 46 girls) and 3 boys with FS in 2 years. The annual incidence rate of GBS in our patients <15 years old was 0.45/100,000, similar to other countries. Infection preceded the onset of symptoms in all but 20 of the 115 GBS/FS cases. In England 7 GBS cases received H1N1 (2009) vaccination and 3 others received seasonal vaccination within 6 months of symptom onset: no more than expected by chance. Most GBS cases were too weak to walk (90/112) and most (80) received intravenous immunoglobulin. 13 of the 112 GBS cases needed ventilation. About a third of GBS children had dysautonomia. 114/115 recovered sufficiently to go home. Conclusions. In 1976 a national immunization programme against swine influenza in the United States was discontinued because GBS was associated with vaccination. However we found that the majority of GBS and FS cases were temporally associated with previous infections, with no evidence of a temporal link with pandemic H1N1 (2009) strain vaccination in children. The outcome for GBS and FS after 6 months was better than reported 28 in adult studies. Acknowledgements. Thanks to notifying paediatricans and the BPSU. Department of Health (DH) grant 019/0047: views expressed are not necessarily those of the DH. Parallel session 6: Cerebral palsy Chairs: Florian Heinen and Bernard Dan O31 -­‐ 1568 Neonatal neuroimaging predicts recruitment of contralesional corticospinal tracts following perinatal brain injury van der Aa NE,Verhage CH, Groenendaal F, Vermeulen RJ, de Bode S, van Nieuwenhuizen O, de Vries LS. Dep of Neonatology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands -­‐ [email protected] Objectives: Unilateral perinatal brain injury may result in recruitment of ipsilateral projections originating in the unaffected hemisphere and development of unilateral spastic cerebral palsy (USCP). The aim was to assess the predictive value of neonatal neuroimaging following perinatal brain injury for recruitment of ipsilateral corticospinal tracts. Methods: Neonatal magnetic resonance imaging and cranial ultrasound scans of 37 children (20 males, 17 females; median [range] gestational age 36wk+4 [26+6–42wk+5] and birthweight 2312 ([770-­‐
5230])g with unilateral perinatal arterial ischaemic stroke (n=23) or periventricular haemorrhagic infarction (n=14) were reviewed and scored for involvement of the corticospinal trajectory. Hand function was assessed using the Assisting Hand Assessment (AHA) and Transcranial Magnetic Stimulation (TMS) was performed (age range 7years and 4 months –18 years and 7 months) to determine the type of cortical motor organisation (normal, mixed or ipsilateral). Neuroimaging scores were used to predict TMS patterns. Results: Eighteen children developed USCP (49%), with ipsilateral corticospinal tract projections in 13 children (8 mixed, 5 ipsilateral). AHA scores decreased with increased ipsilateral projections. Asymmetry of the corticospinal tracts seen on neonatal MRI was predictive of development of USCP and recruitment of ipsilateral tracts (positive and negative predictive value of 73% and 91%). Conclusion: Neonatal neuroimaging can predict recruitment of ipsilateral corticospinal tracts. Early knowledge of the expected pattern of cortical motor organisation will allow early identification of children eligible for early therapy. O32 -­‐ 1912 Brain volume reduction in young adults with perinatal hypoxic-­‐ischaemic encephalopathy Bregant T, Rados M, Vasung L, Zadnik V, Derganc M, Evans AC, Neubauer D, Kostovic I. Department of Pediatric Neurology, University Children’s Hospital, University Medical Centre Ljubljana, Slovenia -­‐ [email protected] Objectives: A severe form of perinatal hypoxic-­‐ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequellae while in moderate and mild HIE only discrete cognitive disorders may occur. Imaging biomarkers for long term outcome in children with perinatal HIE are not known. Materials and Methods: MR imaging (3T Magnetom Trio Tim, Siemens) was performed in a cohort of 14 young adults (9 males, 5 females, mean age 22.1±0.7 years) with a history of mild or moderate perinatal HIE defined by Sarnat and Sarnat criteria. The control group consisted of healthy participants (9 males, 5 females, mean age 22.8±0.7 years). Volumetric analysis was done after the MR images processing using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of white and grey matter, and cerebrospinal fluid. We measured volumes, thickness and area of the cerebral cortex in the frontal, parietal, temporal, occipital lobe, and of the cingulated and parahippocampal gyrus, isthmus cinguli, and insula. Results: The HIE patient group showed smaller absolute volumetric data. Statistically significant (p<0.05) reductions of gyrification index in the right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found also in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. Conclusions: Our analysis showed general total brain volume reduction in HIE patients with predilection changes in the temporal lobes and parahippocampal gyrus. O33 -­‐ 2123 Visual spatial perceptual profiles in children with Developmental Coordination Disorder or in very premature children with Cerebral Palsy Gonzalez Monge S, Praticien Hospitalier, Lyon, France -­‐ sibylle.gonzalez-­‐[email protected]­‐lyon.fr 29 The visual-­‐spatial function appears to be particularly sensitive to neuro-­‐cognitive developmental disorders. This emphasizes the clinical importance of using tools to specifically test the visuo-­‐spatial function during development. The aim of our study was to compare the visual spatial perceptual profiles in two groups of children with Developmental Coordination Disorder (DCD) or with Cerebral Palsy (CP) (i e without or with early cerebral lesions). We selected two groups of children aged 8 to 12 years old. Ten children were identified as having DCD following DSM-­‐IV-­‐TR criteria and a score below the 5% cut-­‐off point on M-­‐ABC-­‐2 (Movement Assessment Battery for Children-­‐Second Edition) and ten children with following criteria: diagnosis of Spastic Diplegia (SD), gestational age at birth was inferior to 33 weeks, diagnosis of Periventicular Leukomalacia documented by brain MRI. Each child had a full-­‐scale IQ-­‐score above 70 on WISC-­‐IV (Wechsler Intelligence Scale for Children-­‐Fourth Edition) and a low score on block design test (Perceptual Reasoning Index). All children were assessed with the DTVP-­‐2 (Developmental Test of Visual Perception-­‐Second Edition) measuring visual perceptual skills (NMVPQ, Non Motor Visual Perceptual Quotient) and visual motor integration nskills (VMIQ, Visual Motor Integration Quotient). In 8 out of 10 very premature children with SD, concerning the DTVP profile, the VMIQ was lower than the NMVPQ and concerning MRI data, these children presented a posterior parietal white matter (or dorsal stream) involvement. The same DTVP's profile was obtained in 5 out of 10 children identified as having DCD and these results suggest that the dorsal stream could be involved, in the same way, in a neurocognitive developmental disorder without identified cerebral lesion. To conclude, the comparison of both neurocognitive developmental disorders could shed light on neuroanatomical bases of visual spatial perceptual impairment in children. O34 -­‐ 1931 Innovative application of the motion graph deviation indexes for the quantification of the pre-­‐post BTX -­‐ A upper limb movement changes Darras N, Vanezis T, Tziomaki M, Pasparakis D and Papavasiliou A. Elepap gait analysis and motion analysis center, Athens, Greece -­‐ [email protected] The kinematic assessment of upper limb function requires the examination of a variety of tasks; this produces a very large set of data that is difficult to clinically analyze. We aimed to apply a new method that simplifies and enhances the quantitative assessment of upper limb performance pre and post Botulinum Toxin A (BTX-­‐A) injection; this method has been previously used in Gait Analysis and produces Motion Graph Deviation Indexes (MGDIs) that enable the examiner to summarize and directly compare graph information from different parameters and motions. Methods: Twenty Typically Developing subjects (age = 14.2 ± 6.6) were used for creating the Normal graphs. One patient with dystonia and two with spasticity were assessed pre and four weeks post BTX-­‐A application. All subjects completed four “reach to grasp” and four gross motor tasks. The examiners were blind regarding injection sites and procedures. Kinematic calculations were based on the recommendations of the International Society of Biomechanics. MGDIs were calculated. Motion Indexes (MI) and Graph Indexes (GI) were created from the average MGDIs, representing the subject's deviation at a specific motion and at each graph respectively. Finally the Global Upper Limb Deviation Index was calculated from the averaged MI's demonstrating the overall subject deviation and four Body Level Indexes averaging the MGDIs of the Head-­‐Trunk, Shoulder, Elbow and Wrist graphs of all motions. Pre-­‐Post BTX-­‐A index differences were calculated. The results were used to identify the Body Levels that showed changes on the Pre-­‐Post BTX-­‐A indexes. Results: The use of the four Body Level Indexes enabled the prediction of the areas that BTX-­‐A was injected with 70-­‐100% accuracy. Conclusion: This Upper Limb assessment protocol and the application of MGDIs were sensitive in recording and identifying the movement changes after BTX-­‐A treatment. O35 -­‐ 1861 Cerebral Visual Impairment and Cerebral Palsy: two sides of the same coin? Fazz E, Galli J, Micheletti S, Rossi A, Franzoni A. Civil Hospital -­‐ Brescia Ð, Italy -­‐ [email protected] Aim: the Cerebral Visual Impairment (CVI) (neurological disorder caused by damage to or malfunctioning of the retrogeniculate visual pathways) has been recognised as an important part of clinical manifestations in Cerebral palsy (CP). CP and CVI share a common origin; the literature shows that 60-­‐70% of children with CP also have CVI. We set out to describe CVI in children with CP. A further aim was to establish whether different types of CP are associated with different patterns of visual involvement. Methods: 129 patients with CP and CVI underwent an assessment protocol including neurological examination, developmental (Griffiths Mental Development Scales50) and/or cognitive assessment (Wechsler Scales of Intelligence51), neuro-­‐ ophthalmological evaluation (using the Hirschberg Test of corneal reflexes 42), the Cover Test and the Paliaga Test 43 to detect strabismus; Teller Acuity Cards 44, Lea Symbols 45 or letter optotypes to evaluate visual acuity; Hiding Heidi Low Contrast “Face” Test 46 to determine contrast sensitivity; using a semirigid screen covered with black and white square 30 patterns in front of the infant’s face to test the optokinetic nystagmus 47, evaluating the behavioural reactions to the kinetic perimetry to assess the visual field 48 and Lang Stereotest 49 to verify stereopsis) and neuroradiological investigations. Results: Visual dysfunction in diplegia was characterised mainly by refractive errors (75% of cases), strabismus (90%), abnormal saccadic movements (86%), reduced visual acuity(82%). The subjects with hemiplegia showed strabismus (71%), refractive errors (88%); oculomotor involvement was less frequent (59%). This group had the largest percentage of patients with altered visual field (64%). Children with tetraplegia showed a severe neuro-­‐ophthalmological profile, characterised by ocular abnormalities (98%), oculomotor dysfunction (100%) and reduced visual acuity (98%). Interpretation: Neuro-­‐ophthalmological disorders are a main symptom in CP, associated with a distinct neuro-­‐ophthalmological profile. Early and careful neuro-­‐ophthalmological assessment of children with CP is essential for an accurate diagnosis and for personalised rehabilitation tools. O36 -­‐ 2035 Clinical Correlation of Arcuate Fasciculus Lateralization in Developmental Dysphasia Komárek V, Vydrová R, Kynèl M, Šanda J, Vránová M, Štìrbová K, Kršek P. Department of Child Neurology, Department of Radiology, Charles University Hospital Motol, Prague, Czech Republic -­‐ [email protected] Objectives: In typically developing children aged 5–13 years, diffusion tension imaging (DTI) demonstrated a relationship between arcuate fasciculus (AF) lateralization and cognitive abilities (receptive vocabulary scores and phonological processing tasks), suggesting that the left-­‐lateralized arrangement of the AF plays an important role in language development as well as in pathophysiology of developmental dysphasia (DD). The aim of this study was to correlate DTI data with clinical severity of language impairment and with specific psychological tests. Methods: We performed DTI in 34 DD subjects. The group consisted of 11 (32%) girls and 23 (68%) boys (6,1 – 12,1 years old, median age 8,7 years). 11 children were evaluated with mild DD, 16 children with moderate DD and 7 children with severe DD. DTI parametres such as fractional anisotropy (FA), apparent diffusion coefficient (ADC), length, volume and count of fibres were established. AF volume laterality index (VLI) was calculated (Left AF–Right AF/Left AF+Right AF). Psychological assessment included examination of IQ, memory, verbal fluency, auditory and visual perception. Statistical analysis was performed using ANOVA. Results: Left AF was identified in 34 children and right AF was found in 32 subjects. VLI ≥ 0,2 corresponding with leftward AF laterality was found in 14 (41%) children, in 3 (21%) girls and in 11 (79%) males. Leftward AF laterality was found in 3 of 11 (27%) children with mild DD, in 6 of 16 (38%) with moderate DD and in 5 of 7 (71%) children with severe DD (P=0.19). Correlations between the DTI parameters (FA, ADC, VLI), neuropsychological scores and severity of DD were not statistically significant. Conclusions: Arcuate fasciculus laterality alone is not related to severity of DD. Altered development of other structures, extrema capsula fasciculus and uncinatus fasciculus respectively, might play substantial role in specific language impairments. O37 -­‐ 1898 Use of serious gaming to increase motivation of cerebral palsy children during rehabilitation Bonnechère B, Jansen B, Omelina L, Da Silva L, Mougeat J, Heymans V, Vandeuren A, Rooze M, Van Sint Jan S, Laboratory of Anatomy, Biomechanics and Organogenesis (LABO), Université Libre de Bruxelles, Belgium -­‐ [email protected] Patient motivation is an important factor to take into consideration since patients, and more particularly young patient suffering of severe diseases such as Cerebral Palsy (CP), must adhere to a rehabilitation scheme as strict as possible. Patient motivation is the main key to a successful rehabilitation scheme. A main challenge is therefore to keep patients motivated enough despite the feelings they could have of “inefficiency”, “lack of progress”, “tiredness”, etc. Serious Gaming (SG) includes games that are developed for a particular purpose (e.g. rehabilitation) other than pure entertainment. Previous works studied the interplay between motivation, rehabilitation and SG. SG can be a good tool to increase children motivation but there is still a lack of evidence and studies are required to evaluate possibilities of SG for CP children. Six mini-­‐games have been developed for the revalidation of CP children. Two different situations were assessed. During the first one (T1) 11 CP children (9.2 (2) years old GMFCS: 1.1 (0.4)) played the game 20 minutes per day during 5 consecutive days (daily use). For the second one (T2) 10 CP children (11.2 (3) years old GMFCS: 2 (0.8)) played the game 20 minutes per day twice a week during 4 weeks. For both T1 and T2 SG was added to conventional rehabilitation. For T1 we used a visual analytic scale to evaluate enjoyment and pain during SG. Compared to conventional rehabilitation children, better enjoyed SG (p=0.04) and experienced less pain (p=0.04) during exercises. For T2 a quality of life questionnaire (Disabkids) was used. Children tended to improve (pre=38.7, post=40.5) but results are not significant (p=0.07). These first results suggests that SG can be used into conventional rehabilitation with positive influence on enjoyment and pain experience during exercises and may improve quality of life of CP children. 31 O38 -­‐ 1645 Brain lesions relate to gait pathology in children with unilateral and bilateral cerebral palsy Van Gestel L, Ortibus E, Meyns P, De Cock P, Sunaert S, Feys H, Duysens J, Jaspers E, Desloovere K. Dep. of Rehabilitation Sciences, Fac. of Kinesiology and Rehabilitation Sciences, KULeuven, Belgium -­‐ [email protected] Objectives: To unravel the complex relations between the broad range of brain lesions in children with cerebral palsy (CP) and their characteristic primary motor deficits and gait pathologies. Materials and methods: 51 children with CP (25 bilateral, 26 unilateral involvement) were enrolled. The following neurological parameters were evaluated qualitatively: corpus callosum (CC) (anterior, mid, posterior), cerebellum, basal ganglia (BG), and brainstem. Two groups of quantitative parameters were extracted: 1) integrity of periventricular / middle / subcortical white matter, summarized in sub-­‐ and global scores; 2) length and volume of the corpus callosum, volume of the lateral ventricles, and brainstem asymmetry. Gait pathology was evaluated by means of the Gait Profile Score (GPS). Primary motor deficits, more specifically lower limb muscle strength and spasticity, were evaluated by means of manual muscle testing and modified Ashworth scale respectively. Separate statistical analyses were conducted for the bilateral (BilG) and unilateral group (UniG). Spearman correlation coefficients, one-­‐ way ANOVA’s and Mann-­‐Whitney U tests (p<.05) related neurological to motor parameters. Results: BilG: Spasticity correlated moderately with CC volume (r=-­‐0.46) and BG-­‐brainstem scores (r=0.44). Significantly higher spasticity scores were found for children with affected contra-­‐ and ipsilateral posterior limb of the internal capsule (PLIC). Muscle strength correlated moderately with BG-­‐brainstem scores (r=-­‐0.56) and was significantly lower with affected anterior body of the CC, or the contra-­‐ or ipsilateral PLIC. GPS scores correlated moderately with the total brain lesion scores (r=0.53) and with bilateral lesion scores of the middle white matter(r= 0.41). Significantly higher GPS scores were found in children with affected subcortical white matter, contra-­‐ or ipsilateral PLIC. UG: Spasticity correlated moderately with the integrity of the ipsilateral middle white matter (r=0.45), while the CC length correlated moderately with the GPS scores (r=0.40). Conclusions: This study highlights several potential relations between brain lesions and gait pathology in children with CP. Thursday 26 September 2013 Parallel session 8: Neurogenetic Disorders Chairs: Marie Cecile Nassogne and Paolo Curatolo O39 -­‐ 1826 Natural course of pontocerebellar hypoplasia type 2 Sánchez-­‐Albisua I, Frölich S , Krägeloh-­‐Mann I. University Children’s Hospital, Tübingen, Germany -­‐ [email protected]­‐tuebingen.de Introduction: Pontocerebellar hypoplasia Type 2 (PCH2) is a rare neurodegenerative autosomal recessive condition and defined on MRI by a small cerebellum and ventral pons. Ninety percent carry a p.A307S mutation in the TSEN54-­‐gene. Clinical features are: mental retardation, microcephaly and dyskinesia. Clinical features haven’t been detailed exhaustively and don’t include the natural course. Patients and methods: Patients were recruited by contacting German patients’ organizations. Inclusion criteria were imaging findings of PCH2 and a p.A307S mutation. Data from 33 patients were collected using physicians’ reports and patient questionnaires. Results: -­‐ General symptoms: feeding difficulties (100%), sleep disorder (96%), apneas (67%) and recurrent infections (52%). Seventy-­‐three percent of children were diagnosed with gastroesophageal reflux disease. A percutaneous endoscopic gastrostomy was necessary in 67% and a Nissen-­‐ funduplication in 36%. -­‐ Neurologic symptoms: Choreathetosis was present in 88% (62% with spasticity), 12% pure spasticity. Seizures occurred in 79%, status epilepticus in 39%. Epilepsy was drug resistant in 70%. Dystonic attacks occurred in 30%. -­‐ Neurodevelopmental data: All children made progress at a rudimentary level: consistent response to certain familiar objects (88%), fixing and following (76%), attempting to grasp objects (76%), moderate head control (73%), social smile (70%), rolling from prone to supine (58%), production of certain sounds to express approval/disapproval (55%), grasping and holding objects (24%), locomotion in the prone position (9%), sitting without support (9%). Ten percent lost achieved abilities on follow-­‐up. -­‐ Anthropometric measurements: Weight, length and head circumference were in the normal range at birth and became abnormal, especially head circumference (-­‐5.6 SD at age 5). Conclusion: Although PCH2 is considered a degenerative disorder, affected children can make some progress. Affected patients require a very intensive care. 32 O40 -­‐ 2159 Hypomyelinating leukodystrophy due to recessive mutations of GJC2 (connexin 47): clinical and radiological characteristics in 18 patients Renaldo F, Tonduti D, Dorboz I, Masliah J, Giraud, G, Elmaleh M, Orivoli S, Beraud-­‐Majorel C, Drunat S, Chalard F, Barthez M A, Desguerre I, Quijano-­‐Roy S, Rodriguez D, Boespflug-­‐Tanguy O. Centre de Référence des Leucodystrophies, Service de Neuropédiatrie et Maladies Métaboliques; Hôpital Robert Debré, AP-­‐HP, Paris, France -­‐ [email protected] Hypomyelinating leukoencephalopathies (HDL) are a heterogeneous group of childhood genetic disorders characterized by a reduced formation of myelin in the central nervous system. The prototypic early-­‐onset hypomyelinating leukoencephalopathy is Pelizaeus– Merzbacher disease (PMD), an X-­‐linked condition caused by mutations in the proteolipid protein (PLP) gene (Xq22). PLP1 mutations can also cause “pure” or “complicated” spastic paraplegia type 2 (SPG2), an allelic disorder at the same locus. Besides PMD, a growing number of Pelizaeus– Merzbacher-­‐like disease (PMLD) are reported, not associated with PLP1 mutations. Autosomal recessive mutations in GJC2 (GJA12, 1q42), encoding the connexin 47, can give rise to PMLD (HDL2) or spastic paraplegia type 44 (SPG44). We report initial and evolving characteristics in 18 GJC2-­‐mutated patients. First we noted a large phenotypic variability, from the classic PMD-­‐like phenotype to the much milder SPG form which can manifest in childhood or in adulthood. This important variability was also observed inside a large consanguineous family. Most of patients experienced early nystagmus as first symptom, associated with psychomotor delay although neurocognitive capacities were higher compared to PMD. The evolution was then marked by the occurrence of a progressive cerebello-­‐spastic syndrome, extra-­‐pyramidal symptoms in some patients, followed by motor and cognitive regression, sometimes loss of language skills, focal epilepsy, and frequently early optic atrophy. Evoked potentials showed more variable and moderate delayed central conductions than in PMD. Nerve conduction velocities were normal. Magnetic resonance imaging (MRI) displayed diffuse hypomyelinating leukodystrophy associated with brainstem abnormalities in all patients. We found other peculiarities in a few patients. The clinical spectrum of GJC2 mutations is broader than PLP1 mutations with intra-­‐family heterogeneity. Clinico-­‐electrophysio-­‐radiological specificities can make it possible to study GJC2 of first intention even among boys. O41 -­‐ 1941 Mutation spectrum and clinical characteristics in Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-­‐ABC) Hamilton EM, Vanderver A, Siriwardena K, Pinelli L, Schiffmann R, Blaser S, Naidu S, van Berkel CG, Polder E, Abbink TE, Wolf NI, van der Knaap MS, VUMC, Amsterdam, The Netherlands -­‐ [email protected] Objectives: Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-­‐ ABC) is a rare hereditary leukoencephalopathy that was identified by MRI pattern analysis.1 Exome sequencing in 11 H-­‐ABC patients recently revealed the same de novo mutation in the TUBB4A gene, which encodes β-­‐tubulin and is highly expressed in neuronal cells. 2 Mutations in TUBB4A are also associated with adult onset dystonias. We here describe the mutation spectrum, clinical phenotype and MRI characteristics in our cohort of 44 H-­‐ABC patients. Materials and Methods: We initiated a cross-­‐sectional observational study in our database of H-­‐ABC patients. Sequential MRIs of patients were evaluated via a standard protocol. In all patients, DNA analysis and a clinical inventory were executed. Results: DNA analysis confirmed that the TUBB4A mutation, observed in the first 11 H-­‐ ABC patients, is by far the most common. Additionally, several other mutations were found. Preliminary results are suggestive of a genotype-­‐phenotype correlation, with a phenotypic continuum extending from neonatal up to childhood disease onset, normal to delayed early development and slowly to more rapidly progressive neurological deterioration. Six patients have died (age 1.7-­‐25 years). The oldest patient is now over 30 years. MRI showed disappearance of the putamen and a variable degree of cerebellar atrophy and cerebral atrophy, largely corresponding to the disease severity. Apart from hypomyelination, myelin loss was evident in some patients. Conclusions: H-­‐ABC is an MRI based diagnosis and the current study further delineates the clinical course and mutation spectrum in this rare leukoencephalopathy. TUBB4A mutations are associated with different neurological disorders, sharing certain characteristics. H-­‐ABC patients show a rather homogeneous phenotype with a distinctive MRI pattern and a variable disease severity. 1 M.S. van der Knaap, et al., AJNR 2002 2 Simons C, et al., Am J Hum Genet. 2013 33 O42 -­‐ 1909 FOXG1 gene: phenotype Ðgenotype relation in Spanish patients Pineda Marfa M, O’Callaghan Gordo M, Gerotina Mora E, Quandt Herrera E, Rabaza Gairí M, Brandi Tarrau N; Cortès Saladelafont E, Roche Martínez A, Armstrong Morón J, Fundació Hospital Sant Joan de Déu and CIBERER, ISCIII1. Servei Neuropediatra y genética molecular. Hospital Sant Joan de Deu2, Barcelona. Spain -­‐ [email protected] Introduction: Rett syndrome (RTT) is a neurodevelopmental disorder, of early onset, affecting almost exclusively girls. The disease has classical forms and atypical variants forms. Most cases are due to mutations in the MECP2 gene, but other genes had been described causing atypical forms of the disease: CDKL5 early epilepsy variant and FOXG1 congenital variant. FOXG1 (MIM 614364) is the first gene linked to autosomal RTT, located on chromosome 14q12 Materials and methods: We have studied the FOXG1 gene by direct sequencing and MLPA (Probemix-­‐P075, MC-­‐Holland) in patients RTT-­‐without MECP2 mutation and in patients with mental retardation and Rett-­‐like clinical features. Results: we analyzed 211 patients with clinical presentation likely to have mutations in FOXG1 gene. We detected 9 patients: six of them had point mutations and three large rearrangements in FOXG1. At the moment of diagnosis the ages ranged from 1 to 9 years old and the gender was 4 males/5 females All had severe early postnatal encephalopathy with deceleration of head growth in the first months of life (1-­‐9 months) with severe microcephaly from early childhood (-­‐3ds/-­‐ 4ds), severe developmental delay, hypotonia, none of them has acquired independent walking and only 3 are able to seat unaided, absent language development, hand stereotypies, convergent strabismus, tongue protrusion, jerky arm movements, bruxism and epilepsy 5 patients. Brain imaging studies showed simplified gyral pattern, reduced white matter volume in frontal lobes and corpus callosum hypogenesis. VIDEO Conclusions: Genetic etiologies of variant Rett syndrome are heterogeneous; screening the FOXG1 gene should be done not only in females, but also in male patients with clinical features of congenital phenotype Rett syndrome and in severe developmental encephalopathies. FOXG1 is not an X-­‐linked gene and therefore there can be a higher incidence of mutation detection in RTT-­‐like males than in MECP2 and CDKL5 genes. O43 -­‐ 1896 The neurology of rhizomelic chondrodysplasia punctata Bams-­‐Mengerink AM, Koelman JHTM, Waterham H, Barth PG, Poll-­‐The BT. Academic Medical Centre, Amsterdam, The Netherlands -­‐ [email protected] Background: To describe the neurologic profiles of Rhizomelic chondrodysplasia punctata (RCDP), a peroxisomal disorder clinically characterized by skeletal abnormalities, congenital cataracts, severe growth and developmental impairments and immobility of joints. Defective plasmalogen biosynthesis is the main biochemical feature. Methods: Observational study including review of clinical and biochemical abnormalities, genotype, presence of seizures and neurophysiological studies of a cohort of 16 patients with RCDP. Results: Patients with the severe phenotype nearly failed to achieve any motor or cognitive skills, whereas patients with the milder phenotype had profound intellectual disability but were able to walk and had verbal communication skills. Eighty-­‐eight percent of patients developed epileptic seizures. The age of onset paralleled the severity of the clinical and biochemical phenotype. Myoclonic jerks, followed by atypical absences were most frequently observed. All patients with clinical seizures had interictal encephalographic evidence of epilepsy. Visual evoked (VEP) and brain auditory potential (BAEP) studies showed initial normal latency times in 93% of patients. Deterioration of VEP occurred in a minority in both the severe and the milder phenotype. BAEP and somatosensory evoked potentials (SSEP) were more likely to become abnormal in the severe phenotype. Plasmalogens were deficient in all patients. In the milder phenotype levels of plasmalogens were significantly higher in erythrocytes than in the severe phenotype. Phytanic acid levels ranged from normal to severely increased, but had no relation with the neurological phenotype. Conclusion: Neurodevelopmental deficits and age-­‐related occurrence of seizures are characteristic of RCDP and are related to the rest-­‐activity in plasmalogen biosynthesis. Evoked potential studies are more likely to become abnormal in the severe phenotype, but are of no predictive value in single cases of RCDP. O44 -­‐ 1703 Deficiency of the E3 ubiquitin ligase TRIM2 causes early-­‐onset axonal neuropathy Ylikallio E, Pöyhönen R, Hilander T, Paetau A, Lönnqvist T, Tyynismaa H. Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland -­‐ [email protected] 34 Purpose: To reveal the genetic etiology of an early-­‐onset axonal neuropathy. Patient: Our patient is a 19-­‐year-­‐
old female with severe neuropathy. She was born in a family with no consanguinity and had normal early development. At the age of 4 years she was sent to Children’s Hospital in Helsinki because of muscle hypotonia. She was alert, but very lean with small muscle mass and muscle atrophy in hands and feet. The deep tendon reflexes were absent. ENMG showed polyneuropathy: in upper extremities the motor nerve conduction velocities were slow with increased distal latencies and low amplitude. The sensory amplitudes were low in upper extremities, and in lower extremities even the motor responses could not be measured. The sural nerve biopsy findings at the age of 5 years were consistent with an axonal neuropathy revealing a mild to moderate loss of prominently large myelinated fibers (MF), but no clear signs of active demyelination, hypertrophy or regeneration. In electron microscopy the axoplasm of slightly swollen large MF revealed prominent neurofilament content. Genetic studies: A whole-­‐exome sequencing revealed compound heterozygous mutations: a missense mutation (c.680A>T) and a 1-­‐bp deletion (c.1699delA) in the tripartite motif containing 2 (TRIM2) gene. The patient carried both the mutations whereas her father was heterozygous for the deletion and her mother for the missense mutation. TRIM2 is a RING finger protein that functions as an E3 ubiquitin ligase. The studies on fibroblasts showed that the mutations resulted in a severe reduction of TRIM2 in the patient’s cells resembling a mouse model for Trim2 which has shown neurofilament disorganization in axons presumably because of deficient ubiquitination. Consistently, our patient’s sural nerve biopsy showed axonal degeneration with disorganized accumulation of neurofilament. Conclusion: TRIM2 is a disease gene for early-­‐
onset, severe CMT2 with inefficient neurofilament degradation as a pathogenic mechanism. O45 -­‐ 1612 RATE: randomised clinical trial of rapamycin in children with Tuberous Sclerosis Complex and intractable epilepsy Overwater IE, Rietman A, Bindels-­‐de Heus GCB, Moll HA, Elgersma Y, Wit MCY. Neurology, Neuroscience; ENCORE Expertise centre for neurodevelopmental disorders -­‐ [email protected] Tuberous Sclerosis Complex (TSC) is caused by inactivating mutations in the TSC1 or TSC2 gene. Mutations in these genes cause disinhibition of the mTOR pathway, which is involved in several cellular pathways, including cell proliferation and control of synaptic plasticity. TSC patients suffer from hamartomatous growths in various organs, including renal angiomyolipoma (AML). CNS manifestations include tubers, subependymal nodules and subependymal giant cell astrocytoma (SEGA). Up to 90% of TSC patients suffer from epilepsy, with 50% of patients intractable to anti-­‐epileptic drugs. Recent clinical trials have shown a decrease in AML and SEGA volume upon treatment with mTOR inhibiting drugs. In animal models of TSC, mTOR inhibitors decrease seizures and improve EEG findings. Rapamycin (sirolimus) is an inhibitor of the mTOR pathway, and has been used in various animal and patient studies. In the TSC clinic of the ENCORE expertise center for neurodevelopmental disorders at the Erasmus MC-­‐Sophia Children’s Hospital, we are currently performing a randomized clinical trial into the effect of rapamycin on epilepsy in TSC patients. Eligible children, with a definite diagnosis of TSC and intractable epilepsy, participate in the trial during one year, and are randomised to receive add-­‐on oral rapamycin treatment during the first or second six months of trial participation. Primary outcome of the trial is seizure frequency, assessed by an epilepsy diary kept by the parents. EEG and developmental examination are secondary outcomes, and are performed upon inclusion and after the first and second six months. Developmental examination includes mental, motor and behavioural functioning. To monitor safety, blood samples to determine rapamycin trough levels, renal and liver function and blood cell counts are taken regularly. Currently, 20 patients have been included in the RATE trial. Design, progression and preliminary results of the trial will be presented. O46 -­‐ 1548 Long term follow-­‐up of clinical and neurographical abnormalities in eight Croatian patients with triple A syndrome Barisic N, Dumic M, Kusec V, Lehman I, Bunoza B, Grdjan P, Ivanja V. Department of Pediatrics, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, Zagreb, Croatia -­‐ [email protected] Objective. To analyse long term follow up of neurological abnormalities (during 2 years to 23 years) in eight Croatian patients with triple A syndrome. Background. The triple A syndrome is caused by autosomal recessively inherited mutation in AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. This multisystemic disease is characterized by achalasia, alacrimia, adrenal insufficiency and neurological impairment. Design/Methods.Clinical examination, electromyoneurography (EMNG) and molecular-­‐genetic analysis were performed in eight patients with triple A syndrome (five males and three females). Results. At the 35 time of diagnosis all patients (aged 2 years to 8 years) presented with alacrimia, latent or manifest adrenal insufficiency, anisocoria in 2, optic atrophy in 4, motor and sensory polyneuropathy on the first exam in 2 siblings, muscle weakness and hypotrophy of distal muscle groups, cavus feet, hyperreflexia but absent triceps surae jerks, talocrural joints contractures, tremor and dysmetria in 5 patients. First EMG findings were normal at the age 6-­‐11 years in 6/8 patients. The follow up EMG showed chronic partial denervation in all patients. Spontaneus activity (fibrillations) was registered in 3/8, compound muscle action potentials (CMAP) were polyphasic in 6/8 patients. Absent or low CMAP amplitude (0-­‐0,5mV) was obtained in 6/8, decreased motor conduction velocity (29-­‐40 m/s) in 8/8, absent F-­‐wave potentials in 7/8, absent neural potentials in 5/8 and proximal conduction block in 5 patients. Mutation pSer263Pro was identified in 5 of 8 patients. One is homozygous and four are compound heterozygous for this mutation. Genotype/phenotype analysis confirmed lack of correlation in patients with triple A syndrome. Conclusions. Long term follow up neurography in patients with triple A syndrome showed progressive mixed motor and sensory polyneuropathy development with signs of pronounced demyelination and/or probably secondary axonal damage. Molecular results support the hypothesis that the pSer263Pro mutation is founder mutation in Slavic population. O47 -­‐ 1530 Outcome of surgical treatment of 64 TSC-­‐associated subependymal giant cell astrocytomas Kotulska K, Roszkowski M, Mandera M, Daszkiewicz P, Grajkowska W, Jurkiewicz E, Borkowska J, Jozwiak S. The Childrens Memorial Health Institute, Warshaw Poland -­‐ [email protected] Objectives: Subependymal giant cell astrocytoma (SEGA) is a brain tumor associated with TSC. Nowadays there are two treatment options in SEGAs: surgery or mTOR inhibitor. The analysis of outcome of SEGA surgery may help characterize the patients who may benefit from pharmacotherapy. Material and Methods: Sixty-­‐four SEGA surgeries in 57 TSC patients, operated on between 1994 and 2011, in whom at least 12-­‐month follow-­‐up after surgery was known were included in the study. The indication for the surgery, tumor size, age of the patients, and post-­‐surgical complications were analyzed. Results: Mean age of patients at surgery was 9.7 years (ranging from 6 weeks to 26 years). Mean follow up after surgery was 63.7 months (median 60 months). Thirty-­‐seven (57.8%) tumors were operated on because the patients developed clinical symptoms, and 27 (42.2%) tumors were resected due to documented tumor growth and/or hydrocephalus revealed on neuroimaging. Surgery-­‐
related complications were reported in 0%, 46%, 83%, 81%, and 67% of patients with tumors maximum diameter below 2 cm, between 2 and 3 cm, between 3 and 4 cm, more than 4 cm, and bilateral SEGAs, respectively. Four patients (6.2% of all surgeries) died during the first week after surgery. Most common complications included: hemiparesis (22%), hydrocephalus (20%), haematoma (14%), and cognitive decline (6%). Complications were more common in children under the age of 3 years (83%) than in older patients (55%). Fifteen patients developed contralateral SEGA in 6-­‐120 months after first surgery. Conclusions: Our study indicates that SEGA surgery is associated with significant risk, especially in cases of bilateral SEGAs, tumors bigger than 2 cm, and children below 3 years of age. Therefore, TSC patients should be thoroughly screened for SEGA growth, and early surgery should be considered in selected cases. Parallel session 9: Varia Chairs: Vladimir Komarek and Colin Kennedy O48 -­‐ 1975 The Presenting Features of Arterial Ischaemic Stroke in a Population-­‐Based Cohort Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, Parker AP, Wassmer E, Wraige E, Amin S, Edwards HB, O’Callaghan FJ. University of Bristol, UK -­‐ [email protected] Objectives: To describe the presenting features of childhood arterial ischaemic stroke (AIS) and analyse factors associated with such features. Materials and Methods: The cases notes of a population-­‐based cohort of 96 children (aged >28 days to <16 years) residing in southern England who experienced AIS between July 2008 and June 2009 were analysed. Presenting features and risk factors were categorised according to schemes used by the International Pediatric Stroke Study. The commonly used adult stroke recognition tool, the FAST (Face Arm Speech Time) test was applied retrospectively. Results: Focal features (hemiparesis, facial weakness, speech disturbance, visual disturbance, and other focal features) were present in 85% of children, diffuse features (decreased conscious level, headache, vomiting, papilloedema, and other diffuse features) in 61% and seizures in 29%. A hemiparesis was present in 72% of children. 78% of children had a least one positive variable (facial weakness, arm weakness, or speech disturbance) on the FAST test. Diffuse features occurred more frequently with increasing age (odds ratio 1.14 [95%CI 1.03 -­‐ 1.26], p=0.015). Seizures were less likely with increasing age 36 (OR 0.83 [95%CI 0.72 -­‐ 0.96], p=0.012). 75% of children under the age of 1 year had seizures at presentation. A positive FAST test was not associated with age. Diffuse features were independently associated with acute systemic risk factors (OR 5.36 [95%CI 1.72 -­‐ 16.7], p=0.004). Arteriopathy was independently associated with a reduced risk of seizures (OR 0.18 [95%CI 0.04 -­‐ 0.86], p=0.031). Children with acute systemic risk factors had reduced odds of a positive FAST test (OR 0.23 [95%CI 0.08 -­‐ 0.69], p=0.009). Presenting features did not significantly vary with gender. Conclusions: The presenting features of AIS in children are similar to those in adult AIS. However, presenting features vary according to age and underlying risk factors. O49 -­‐ 2118 A clinical advisory board for a rare disease (Prader-­‐Willi syndrome) Blichfeldt S, Farholt S. Herlev University Hospital, Pædiatric Department, 2730 Herlev Denmark -­‐ [email protected] Prader-­‐Willi Syndrome (PWS) is characterized by neonatal hypotonia, hypogonadism, growth retardation, mental retardation, hyperphagia from age 1-­‐ 3, and a risk of morbid obesity and early death. Behavioral problems and later psychiatric diseases in adults are seen. PWS is caused by lack of paternal gene expression on chromosome 15q. Treatment is multidisciplinary and lifelong involving many different professionals. Objectives: To present the Danish Clinical Advisory Board for PWS (CABPWSDK) of 1991, supported by the Danish PWS association (PWSDK) Method: The CABPWSDK consists of professionals with an extensive experience in PWS. Members are pediatricians, psychiatrist, nurses, dietician, physiotherapist, special teachers, psychologist, social workers and social advisers included staff from the two national PWS centers. The group meets two times yearly beside e-­‐mail contacts. Group members can be contacted directly by families and professionals. Results: The CABPWSDK advices about how to get support and treatment, about diagnostics and treatment possibilities. Articles on medical, social, and educational topics are written for the Danish PWS Newsletter. Group members teach at courses for families and professionals: medical personnel, teachers, daycare staff, caregivers for adults. The PWSDK edits leaflets on topics in PWS supported by the CABPWSD. The regular contact in the CABPWSDK group secures continuous updating about PWS, about ongoing research and meetings in DK and abroad. The CABPWSDK can propose new projects supported by the PWSDK Conclusion: The PWSDK and Danish families appreciate the work by the CABPWSDK, and group members find the contact to the PWSDK and the interdisciplinary contact important ensuring updated and qualified knowledge on PWS for the benefit of the patients. The described model is to be recommended. O50 -­‐ 1933 Normative data of the 6-­‐minute walk test in healthy boys aged 5-­‐12 years and correlations with anthropometric variables and myometry Goemans N, Klingels K, Boons S, Verstraete L, Peeters C, van den Hauwe M, Feys H, Buyse G. Child Neurology, University Hospitals Leuven, Leuven, Belgium -­‐ [email protected] Objectives: The aim of this study was to improve our insights on the 6-­‐minute walk test (6MWT), an outcome measure currently used in clinical trials for ambulant Duchenne patients, by (1) generating normative data in healthy boys aged 5-­‐12 years, and (2) describing the relation with anthropometric variables and myometry. Materials and methods: Participants (n=442) were recruited in eight age categories between 5 and 12 years. Each boy walked 6 minutes (timed with stopwatch) along a 25 meters tape line. Maximal isometric contractions for knee flexion and extension were recorded with a hand-­‐held myometer. Results: For the total group, the 6MWT distance was 582.2m ±88.2 (mean ±SD) with a mean velocity of 97m/min. The 6MWT distance increased significantly with age, from 478.0m ±44.1 at age 5, to 650.0m ±76.8 at age 12, with the steepest increase between 5 and 8 years. Percentile curves of the 6MWT were developed for age and height. Predicted values were calculated according to available reference equations (Geiger and Ben Saad), indicating an overestimation by those equations. Correlations with anthropometric variables were fair to good (age r=0.62, height r=0.58, weight r=0.47). Myometric variables (sum flexors, sum extensors, total sum) showed correlations of 0.46, 0.50, 0.52, respectively. Interestingly, when dividing into two age categories (5-­‐8 years, 9-­‐12 years), these range of correlations only applied to the younger age group, while in the older age group correlations were poor (r=0.08,0.16, 0.15 respectively). Conclusion: The percentile curves according to age and height provide a useful tool in the assessment of ambulatory capacity in boys with variable diseases and more specifically in Duchenne patients. While significant correlations were found with anthropometric variables and myometry in the younger age group, further study is needed to define the additional factors influencing 6MWT, especially in the older age group. 37 O51 -­‐ 2115 Clinical Presentation and genetic causes of Charcot Marie Tooth Disease in a Paediatric Cohort Niermeijer JMF, Rustenburg L, Van Ruissen F, Verhamme C, Baas F, Poll-­‐The BT. Academic Medical Centre, University of Amsterdam, The Netherlands -­‐ [email protected] Introduction: Charcot-­‐Marie-­‐Tooth disease (CMT) is the overlapping term for a group of inherited neuropathies. To date more than 45 responsible genes have been described. With the increasing knowledge of the underlying genetic mechanisms, detailed descriptions of the different phenotypes become more important. Methods: A retrospective cohort study of children with CMT was performed at the department of paediatric neurology of the Academic Medical Centre Amsterdam, a tertiary referral centre for children with neuromuscular disorders. Patients were classified based on the clinical signs, family history, electrophysiological investigations and genetic testing results. Results: Forty-­‐six children with CMT were included. In 23/46 patients NCS were performed. In 29/46 patients (63%) a genetic diagnosis was confirmed. 32 patients were classified as CMT1: 21 PMP22 duplications, 2 MPZ, 3 EGR2 and 1 GJB1 mutation. 14 patients were classified as CMT2. Only in 2/14 a genetic cause was identified yet: 1 GARS and 1 MFN2 mutation, the remainder is still under investigation. The median age of onset was 1.75 years (IQR 1.3 – 3.75 y). Gait disturbances were present in 52% and the most frequent presenting symptom. Three patients developed the first-­‐ severe-­‐ signs of CMT during a course of chemotherapy with vincristine. Only one patient in this cohort had mental retardation, although 5 others had behavioural or learning problems necessitating special schooling. Disease progression and clinical differences between the genetic subtypes will be described in detail. Conclusion: The age at first presentation in this cohort was more early than has been generally assumed. Children with CMT do very often present with the first symptoms during the first three years of life, and families at risk ask for genetic evaluation already early in life. There remains a substantial proportion of CMT2 patients without a genetic diagnosis. Additional sequencing is performed for these patients at this moment. O52 -­‐ 2063 Spectrum of cerebellar and anterior horn cell degeneration caused by EXOSC3 mutations Burglen L, Nguyen S, Cances C, Cuisset JM, Julia S, Metreau J, Lion-­‐François L, Legall A, Amsallem D, Gelot A, Billette de Villemeur T, Rodriguez D. Reference center for cerebellar malformations and congenital diseases and Department of genetics, AP-­‐HP, Hôpital Trousseau and INSERM U676, Paris, France -­‐ [email protected] Pontocerebellar hypoplasia (PCH) associated with spinal cord anterior horn cell loss has been named PCH type 1 by Barth in 1993. PCH1 is an autosomal recessive disease characterized by an early-­‐ often antenatal -­‐onset, with arthrogryposis and limited survival. Recently mutations of the EXOSC3 gene were reported in classical as well as in mildly affected PCH1 patients. Objectives: to describe the phenotype of patients affected with cerebellar and anterior horn cell degeneration caused by EXOSC3 mutations. Patients and methods: Clinical data and MRI from 8 patients affected with cerebellar and anterior horn cell degeneration related to EXOSC3 mutations were reviewed. Results: Two sibs and another patient fit the diagnosis of PCH1: they were affected from birth and presented with hypotonia, proximal muscular deficiency, respiratory and swallowing difficulties. Electromyogram showed neurogenic changes. In the familial case, PCH was evident on the MRI performed at 4 months in the older child but no change was noted at day 4 in the younger. Death occurred at, respectively, 11 months, 15 days and 4 months. In 2 patients, neuropathology showed a severe atrophy of the pons, cerebellum and anterior horn. Patients 4 to 7 presented with a progressive disease which began at 3-­‐5 months. They had severe progressive hypotonia, proximal limb weakness and amyotrophy, nystagmus, spasticity, and increased tendon reflexes. MRI showed progressive cerebellar atrophy and/or cerebellar hypoplasia without brainstem involvement. Patient 8 had a non-­‐progressive psychomotor retardation with PCH on MRI and he was able to sit in the first years of life. At age 10, he started to decline and presented with spastic paraplegia and proximal weakness, nystagmus and respiratory and swallowing difficulties. Conclusion: The gene EXOSC3 is a major PCH1 gene but is responsible for others, milder, phenotypes of cerebellar and anterior horn cell degeneration with cerebellar atrophy without brainstem involvement. O53 -­‐ 1995 Long-­‐term Outcome after Vegetative State due to Near-­‐Drowning and Quality of Life of the Families Kluger G, Kirsch A, Hessenauer M, Lahl O, Steinbeis von Stülpnagel C. Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schöen Klinik Vogtareuth Germany -­‐ [email protected]­‐kliniken.de 38 Objectives: Discussions between emergency medicine, intensive care, rehabilitation and palliative care concerning children in vegetative state lack information about the long-­‐term prognosis and quality of life (QoL) of their families. Methods: At two different time points, we investigated long-­‐term outcome and QoL of the families of 85 children, who were in vegetative state 4 weeks after a near-­‐drowning event, and who were transferred to our institution for early-­‐phase rehabilitation in the years 1986-­‐2001. Assessment 1 was performed in 2001 as anonymous questionnaire, assessment 2 in 2010-­‐2011 as structured telephone interview with both parents separately. Additional interviews were carried out with one parent of children who survived concerning outcome according to Remi-­‐Pro®. Results: Response rate of assessment 1: 53 %; follow-­‐up: 6 months – 15 years after the accident (mean: 5 years). Assessment 2 in 53 / 85 children (62%) and 99 parents with a mean follow-­‐up of 15 years. Outcome: 14 children had died (26%), 5 were in sleep-­‐ wake level (9%), 10 in perception level (19%), 13 in communication level (24%), 2 in independence level (4%), 4 in group level (7%), and 5 in participation level (9%). Many parents reported massive and persisting feelings of guilt. When asked whether it would have been better that their child had died immediately after the accident despite resuscitation, 58 / 99 parents (59%) answered “no”. Independent of the outcome in their children the majority of parents reported a high level of satisfaction with their lives. Conclusion: Our results are in accordance with other investigations in chronic diseases of a non-­‐ linear relationship between physical health status and QoL. Our results can be useful for defining individual therapeutic goals and also support rehabilitation professionals in communicating confidence that long-­‐term QoL of families with children in vegetative state due to acquired brain injuries is often good. O54 -­‐ 1853 Manifestations of Cowden syndrome in childhood Schieving JH, Padberg GWAM, Willemsen MAAP. Radboud University Hospital Nijmegen, Department of Pediatric Neurology Nijmegen, The Netherlands -­‐ [email protected] Cowden syndrome (CS) is caused by a heterozygous germline mutation in the PTEN gene on chromosome 10. It is also called PTEN-­‐hamartome-­‐tumor syndrome because of the high risk to develop benign and malignant tumors in thyroid, breast, endometrium, colon and urogenital tract mainly at adult age. Many attention has been paid to adults with CS, but litte to children with this syndrome. We have seen 24 children with CS on our outpatient clinic of pediatric neurology and present their manifestations here. 50% of the children had an inherited mutation of one of the parents, the other 50% had a de novo mutation. All had birthweight above the 1st percentile, 50% even above the 2nd percentile. Head circumference was progressive in the first year of life and stabilized thereafter. All had also scaphocephaly. Gross motor milestones were delayed, but all children were walking independently at the age of three years. They all had hypotonia and suboptimal gross motor functioning. Verbal expression is a strong point of most children with CS. 40% of the children needed a special education school. Upper respiratory infections were common in infancy. Remarkable was the sweating during the night. Only one child developed a malignancy: an atypical meningeoma. O55 -­‐ 1566 Incidental white matter lesions in children presenting with headache Bayram E, Topcu Y, Karaoglu P, Yis U, Cakmakci HG, Hiz SK Dokuz Eylul University Hospital, Division of Pediatric Neurology Izmir, Turkey -­‐ [email protected] Aim: We aimed to describe the prevalence and significance of white matter lesions detected on magnetic resonance imaging in children with headache. Material and methods: Children who were admitted with the complaint of headache and had a neuroimaging between December 2007 and June 2012 were included in the study. The patients with nonspecific white matter lesions were called for a control visit and current status of headache and neurologic findings were determined. Results: A total of 941 patients were included in the study. 61 % of the patients had cranial neuroimaging. 8.2 % had only cranial computed tomography, 7.5 % had cranial cranial computed tomography and cranial magnetic resonance imaging and 84.3 % had only cranial magnetic resonance imaging. The rate of incidental nonspecific white matter changes detected in our study group was 23/527 (4.4 %) 14 (60.9 %) had migraine without aura, eight (34.8 %) had tension type headache and one (4.3 %) had migraine with aura. All patients with nonspecific white matter changes on magnetic resonance imaging showed normal psychomotor development. The physical and neurologic examinations of all patients were normal. The mean clinical follow up period of the patients was 16.8±17.3 months. No patients showed neurological deterioration during the follow up. The white matter lesions were supratentorial in all patients. The mean size of the lesions was 5.1±4.5 mm. Repeated radiological evaluations were performed in 11 (47.8 %) of the patients. No new white matter lesions were detected in control magnetic resonance imaging’s during 39 follow up Conclusion: Non specific incidental white matter changes may be seen in children with headache. Normal clinical follow up the absence of evident benefits from repeated imaging studies, we suggest that repeated imaging studies are not warranted in every patient, and should be tailored according to clinical course. O56 -­‐ 1721 The role of probabilistic tractography in the surgical treatment of pediatric brainstem gliomas Máté A, Kis D, Vörös E, Barzó P. Department of Neurosurgery, University of Szeged, Szeged, Hungary -­‐ [email protected] Objective: Brainstem gliomas are often considered to be inoperable due to the high surgical risk. However even partial resection of the tumor may considerably increase the efficacy of radiotherapy and can extend survival. This is of special importance in the case of pediatric brainstem gliomas. The localization of the most important anatomical components of the brainstem may significantly decrease surgical risk. Probabilistic tractography is based on diffusion tensor magnetic resonance imaging and enables probabilistic mapping of white matter pathways. Our aim was to investigate whether probabilistic tractography is capable to segment the brainstem by its connections and localize the main ascending and descending pathways in healthy individuals and children with brainstem tumor. Materials and methods: 10 children (age range: 5-­‐17 years) with brainstem gliomas and 15 healthy volunteers (age range: 20-­‐30 years) were included in the study. We performed segmentation of the pons and the midbrain (by their connections to the primary motor cortex, sensory and medial thalamus) and ran fiber tracking from the posterior limb of the internal capsule and the dorsolateral pons. Results: Our results revealed that segmentation of the brainstem by probabilistic tractography correlates well with brainstem anatomy. By fiber tracking we could localize motor, sensory and ascending reticular activating system pathways and unequivocally differentiate between expansive (n=6) and infiltrative (n=4) tumors. Navigation surgery was performed in 5 cases (2 subtotal and 3 partial resections). The patients’ neurological status did not deteriorate postoperatively. Conslusion: According to our results, probabilistic tractography seems to be a promising tool in the preoperative investigation of pediatric brainstem gliomas. Friday 27 September 2013 Parallel session 10: Movement disorders 2 Chairs: Mary King and Sameer Zuberi O57 -­‐ 1880 Progressive ataxia, hyperkinetic movement disorder with myoclonic jerks and falls in a toddler: think of cerebral folate deficiency! Toelle SP, Wille D, Schmitt B, Scheer I, Thöny B, Plecko B. University Children’s Hospital Zurich, Division of Neurology Switserland -­‐ [email protected] Cerebral folate deficiency (CFD) is characterized by decreased concentrations of 5-­‐ methyltetrahydrofolate (5-­‐
MTHF) in CSF in the context of normal systemic folate metabolism. Mutations in the FOLR1 gene lead to a specific inability to transport 5-­‐ MTHF across the blood-­‐brain barrier, resulting in progressive, severe neurological sequelae. A 5-­‐year-­‐old boy presented with progressive ataxia of trunk and limbs, a hyperkinetic movement disorder with myoclonic jerks, head stereotypies associated with abnormal eye movements, and daily attacks with sudden falls. These falls were to some extent triggered by body care as blowing his nose, washing his face or hands. They occurred up to more than 20 times per day, resembling myoclonic astatic seizures with a rapid, brief flexion of the neck and the trunk and extension of the arms, reminiscent of infantile spasms. They lasted only 1-­‐2 seconds but led to head injuries and were refractory to anticonvulsive treatment. The patients’ cognitive and motor abilities deteriorated and he became very impulsive. MRI of the brain revealed hypomyelination and mild cerebellar atrophy, CT showed calcification within the basal ganglia (not visible on MRI), and 5-­‐MTHF in the spinal fluid was measured 0.0 nmol/l whereas plasma folate was normal. The diagnosis of folate transporter deficiency was confirmed by identification of the homozygous nonsense mutation p.R204X in the FOLR1 gene, a mutation that was previously described. Treatment with oral and intravenous folinic acid resulted in impressive brain growth within months documented on imaging and obvious clinical improvement. Young children with ataxia, hyperkinetic movement disorder and seizures, typically combined with abnormal myelination should be screened for CFD, particularly in regard to the treatment option of this severe neurometabolic disorder. Calcifications within the basal ganglia can be a diagnostic finding not reported so far in the context of folate transporter deficiency. 40 O58 -­‐ 2017 Gabapentin can improve dystonia severity, transfers, sitting, sleep, mood and pain in children Liow N, Marianczak J, Kirk E, Tomlin S, Lumsden D, Gimeno H, Kaminska M, Perides S, Lin JP. Complex Motor Disorders Service Children’s Neurosciences Centre, Evelina Children’s Hospital, Guy’s and St. Thomas’ NHS Foundation Trust UK -­‐ [email protected] Objectives: This report examines the precedence and efficacy of gabapentin use with a literature review and retrospective cohort study. Methods: Pubmed and embase literature reviews examined gabapentin use in movement disorders, doses used, adverse effects and graded according to the Oxford CEBM Levels of Evidence criteria. Case-­‐notes of children receiving gabapentin in the last four years were reviewed. Dystonia severity and functional levels were graded using the Dystonia Severity Assessment Plan (DSAP) and International Classification of Functioning, Disability and Health, Children & Youth version (ICF) respectively, before and after the use of gabapentin. ICF domains included seating tolerance, involuntary muscle contractions, sleep amount and quality, and mood, which were graded on a scale from 0 (no impairment/difficulty) to 4 (complete impairment/difficulty). These grades were analysed using Wilcoxon signed-­‐rank tests. Results: 41 reports described the use of gabapentin in the treatment of movement disorders. Highest levels of evidence were found in the treatment of Restless Leg Syndrome: a recent meta-­‐analysis found improvement of symptoms over placebo. Positive reports were also seen in orthostatic tremor, essential tremor and dystonia but limited evidence for gabapentin use in children with dystonia and chorea. 49 children were identified aged 2-­‐18 years. A significant decrease in DSAP ratings was seen following gabapentin treatment (mean before: 2.73, post: 1.68, Z=-­‐
4.682, p<0.01). All selected ICF category means and median values improved significantly, with a median gabapentin dose of 51.5mg/kg/day (SD: 37.0) compared to a median dose of 23.7mg/kg/day (SD: 13.1) in 15 children receiving gabapentin for neuropathic pain. No unexpected side-­‐effects were reported at this higher dose. Conclusion Gabapentin appears to improve dystonia severity, transfers, sleep amount and quality, sitting tolerance, agreeableness/mood, tone, involuntary contractions and pain. Median doses for successful management of dystonia was twice that needed for neuropathic pain in children, however, further research is required. O59 -­‐ 1906 Alternating hemiplegia and ATP1A3 gene: evolution of 12 cases into adulthood. Genotype-­‐Phenotype correlations. Ramirez-­‐Camacho A, Panagiotakaki E, Poncelin D, Nicole S, Lesca G, Arzimanoglou A. Epilepsy, Sleep and Paediatric Neurophysiology Dpt., Femme Mère Enfant Hospital, University Hospitals of Lyon (HCL), France -­‐ [email protected] Introduction: Mutations in ATP1A3 gene as the aetiology of 75% of cases of alternating hemiplegia of childhood (AHC) is a recent major discovery. Natural history and evolution of the disease into adulthood remain topics of debate and of future research. Objectives: To asses evolution 6 years after the last clinical update of French patients, previously included in the European Network for Research on Alternating Hemiplegia (ENRAH) Database. Methods: Patients were contacted through the French Parents Association (AFHA) and they were examined and filmed during its annual meeting. Results: At this occasion 18 patients were re-­‐evaluated (12 adults, 6 children) and 6 cases (all children) were new. Median age of the 12 adult patients was 27.5 years (18-­‐ 38 years). In contrast with hemiplegic attacks, 50% of the adult patients presented with an increase in frequency of the dystonic attacks that became their main type of paroxysmal phenomena. Five patients experienced severe status epilepticus frequently time-­‐related to gait deterioration. Half of the cohort had lost the ability to walk independently and were wheel chair-­‐bound. Only one of them was not epileptic. Seven of twelve patients had a stable clinical course after 6 years while three patients considered « to still make some progress ». Mutations in ATP1A3 gene were identified in nine patients, two had no mutations and genetic analysis is in process in one patient. Conclusion: Our previous results (Panagiotakaki et al, 2010) suggested individual variability in patients with AHC, but a rather steady clinical course in adults when studied as a group. Longer follow-­‐up of this cohort of adult patients shows that motor regression could be frequent, notably in patients with status epilepticus. In light of the discovery of ATP1A3 gene mutations as the aetiology of AHC, genotype-­‐ phenotype correlations will be presented and discussed. O60 -­‐ 1707 Ataxia and areflexia precede progressive myoclonus ataxia in young children with GOSR2 mutation van Egmond ME, Verschuuren-­‐Bemelmans CC, Nibbeling EA, Elting JW, Sival DA, Brouwer OF, de Vries JJ, Kremer HP, Sinke RJ, Tijssen, MA, de Koning TJ. Department of Neurology, University of Groningen, University Medical Center Groningen, The Netherlands -­‐ [email protected] 41 Objectives: Progressive myoclonus ataxia is a descriptive diagnosis characterized by myoclonus, ataxia and infrequent seizures. Possible underlying etiologies include Unverricht-­‐Lundborg disease and mitochondrial encephalopathy, but often the etiology cannot be determined. Recently, a homozygous mutation in the GOSR2 gene (c.430G>T, p.Gly144Trp) was reported in twelve patients with childhood-­‐onset progressive ataxia and myoclonus, denominated as progressive myoclonus epilepsy. The aim of this study is to provide longitudinal clinical descriptions of the natural history, video documentation, neuroimaging and neurophysiological data of five Dutch patients with GOSR2 mutations. Materials and methods: We evaluated five patients with cortical myoclonus, ataxia and areflexia caused by GOSR2 mutations. Results: All five patients (aged 7-­‐26 years) had the same homozygous mutation in GOSR2. All originated from the northern Netherlands and showed a remarkably homogeneous phenotype with ataxia, areflexia, myoclonus and relatively mild epilepsy. Four patients presented with symptoms of unsteady gait and clumsiness between 2-­‐3 years of age. Areflexia and ataxia preceded the multifocal myoclonus and generalized myoclonic seizures. Myoclonus and ataxia have been relentlessly progressive over the years. Electroencephalography showed cortical spikes preceding myoclonic jerks and a prominent photoconvulsive response, indicating cortical reflex myoclonus. Electromyography revealed signs of sensory neuronopathy and/or anterior horn cell involvement. Conclusions: We present new, longitudinal data of the evolution of the GOSR2 phenotype from infancy to adulthood. So far, GOSR2 mutations have been considered in the differential diagnosis of patients with progressive myoclonus epilepsy. Based on the presented data, we would advise to consider mutation analysis of GOSR2 in children and adolescents with progressive myoclonus ataxia as well as in young children with progressive ataxia and areflexia, a clinical picture resembling Friedreich's ataxia. O61 -­‐ 1802 Tyrosine hydroxylase deficiency. The Greek Experience Pons R, Syrengelas D, Gkika A, Dinopoulos A, Orfanou I, Serrano M, Artuch R, Youroukos S, Agia Sofia Hospital, Athens, Greece -­‐ [email protected] Objectives: The objective of this video presentation is to illustrate the evolution of the motor development of 4 patients with tyrosine hydroxylase deficiency. Materials and Methods: All patients were diagnosed based on CSF biogenic amine analysis and sequencing analysis of the TH gene that revealed a homozygous pathogenic mutation in exon 6 (c.707T>C). All patients were started with L-­‐Dopa at 0.5-­‐1mg/k/d. Doses were gradually increased according to tolerance and clinical response. The Gross Motor Function Measure was performed at several points in time. Results: All patients showed improvements in motor development that were objectively quantified on the Gross Motor Function Measure. Patients showed L-­‐dopa induced dyskinesias of variable intensity and they were managed mainly by a slow and gradual increase of the L-­‐dopa dose. Two patients were also managed with amantadine Conclusions: Tyrosine hydroxylase deficiency is a treatable disease. L-­‐dopa induced dyskinesias probably due to dopamine receptor hypersensitivity are tolerable with a slow titration of the L-­‐dopa dosing together with amantadine in some cases. Parallel session 11: Neurometabolic disorders Chairs: Rudy Van Coster and Marjo Vanderknaap O62 -­‐ 1673 The Natural History of Late Infantile CLN2 Disease: Striking Homogeneity of Clinical Progression in Two Independently Obtained Large Clinical Cohorts Schulz A, Nickel M, Downs M, Mezey J, Landy H, Sondhi D, Jacoby D, Wittes J, Crystal R, Kohlschuetter A. Children’s Hospital, University Medical Center Hamburg-­‐Eppendorf, Hamburg, Germany -­‐ [email protected] Late infantile CLN2 disease (CLN2) is a lysosomal storage disease caused by deficient tripeptidyl-­‐peptidase 1 activity and characterized by progressive psychomotor and language decline. The clinical course was originally described quantitatively in a patient cohort using a disease-­‐specific rating scale. Recently, this cohort has been expanded to 29 genetically confirmed patients. This new study focused on (i) first symptoms to support early diagnosis, (ii) prospective longitudinal data acquisition covering a period of 26 years (1986 to 2012), and (iii) quantification of rate of decline as a means to measure disease progression. Results of the study showed the following: (1) Early symptoms of CLN2 comprise delayed language acquisition and seizures (73% of patients; median age of onset 37 months). (2) Disease progression was measured longitudinally by the sums of the 3-­‐point motor and language subscales of the Hamburg-­‐LINCL score. In this cohort, onset of neurological decline occurred at a median of 39 months of age (lower to upper quartile 35-­‐44 months; range 14-­‐84 months). Onset of symptoms leads to a rapid, progressive clinical decline with a linearized mean rate of decline of 2.2 units/year 42 (SD±1.1). Slowly progressing patients were uncommon and mostly related to unusual genotypes. The age-­‐ specific level of functioning was similar in an independent dataset of 62 observations in 43 patients from the Weill Cornell CLN2 cohort. Further, quantification of CNS MRI parameters of the Weill Cornell subjects showed similar status. This analysis of CLN2 natural history shows a high degree of homogeneity in the population across time and geography and supports the use of such data as natural history controls in future therapeutic studies. The data underscore the rapid decline in this disease, and therefore the importance of early diagnosis for potential therapies. CLN2 should be considered in young children with new onset seizures of uncertain etiology. O63 -­‐ 1788 Diagnosing the tip of an iceberg in a potentially treatable neurometabolic disorder: cerebral creatine deficiency syndromes Haliloglu G, Oguz KK, Onol S, Tokatli A, Coskun T, Topcu M. Hacettepe University Children’s Hospital, Department of Pediatric Neurology -­‐ [email protected] Cerebral creatine deficiency syndromes (CCDS) include autosomal recessively inherited synthesis defects (GAMT and AGAT deficiency), and X-­‐linked creatine transporter defect (CRTR). These disorders are characterized by mental retardation, expressive aphasia, autistic behaviour, epilepsy, and movement disorders, and represent a group of neurometabolic diseases, which are potentially treatable. We would like to present clinical and neuroimaging features of 6 children diagnosed with GAMT deficieny, from 5 unrelated families, with long term follow-­‐up (2-­‐6 y) on oral creatine supplementation therapy. In our cohort (F: 2, M: 4) mean age at diagnosis was 11.5 months (6 -­‐ 18 months), mean age at diagnosis was 6.2 y (17 months-­‐11y). Delay in developmental milestones/retardation, autistic spectrum disorder, stereotypical movements, and speech delay were present in all of the patients, and febrile seizures (n= 3), hypoxic insult at birth (n= 2), hypotonia (n= 2), movement disorder (n= 1), indirect hyperbilirubinemia (n= 1), epileptic encephalopathy (n= 1) were additional features. There were increased urinary guanidinoacetate levels (tandem-­‐MS) (n= 6), basal ganglia involvement (n= 4), cerebral creatine deficiency demonstrated by MRS (n= 6), and diagnosis was confirmed by GAMT mutations (n= 5). Neuroimaging findings including basal ganglia involvement and lack of creatine peaks were normalized on 6th month of oral creatine supplementation. Epilepsy, behavioural features, movement disorder responded well to treatment, and time lag between onset of symptoms and age at diagnosis correlated with degree of mental retardation and expressive language (n= 4). Developmental and expressive language delay, hypotonia, seizures, movement disorder, autistic behaviour are core features of CCDS, and this potentially treatable neurometabolic disease should be included in the differential diagnosis. MR-­‐ spectroscopy serves as a valuable tool for both diagnosis and monitorization of therapy. O64 -­‐ 1920 Zellweger spectrum manifestations in adulthood Berendse K, Engelen M, Wanders RJA, Waterham HR. Poll-­‐The BT. Department of Paediatric Neurology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands -­‐ [email protected] Background: Zellweger spectrum disorders (ZSDs) are peroxisomal biogenesis disorders (PBDs) and represent a continuum of different phenotypes. This spectrum is clinically characterized by a variable severity of global neurological involvement, dysmorphism, visual impairment, sensorineural deafness and other systemic manifestations. ZSD patients with severe disease manifestations usually do not survive their first-­‐year of life and patients with a milder phenotype can survive into their first or early second decade. Common biochemical markers in plasma are elevated very long chain fatty acids, bile acid intermediates and branched-­‐chain fatty acids. Furthermore there is an impairment in the plasmalogen biosynthesis. As a result of improved biochemical and clinical characterization, more patients with milder forms of ZSDs are diagnosed. Furthermore, as a consequence of improved health care, more patients will survive and reach adulthood. Currently mutations in PEX-­‐1, -­‐2, -­‐3, -­‐6 and -­‐10 are already associated with milder clinical phenotypes. However an overview of clinical manifestations in adult ZSD patients is currently lacking. Objective: To give an overview of the clinical and biochemical spectrum in adult ZSD patients. Methods: This retrospective study included 10 ZSD patients, regularly followed-­‐up by our hospital teams for neurological and non-­‐neurological symptoms. Results: In our cohort, all patients had a severe visual-­‐ and hearing-­‐ impairment. Verbal communication was possible in 7/10 and the majority is able to walk independently. Surprisingly, none of the patients had epilepsy. A cerebellar syndrome and pyramidal signs were seen in 3 patients and 5 suffered from peripheral polyneuropathy. Normal MRI was seen in 2/10. We only noted progressive leukoencephalopathy in 1 patient. In some patients, we also noticed normalization of abnormal peroxisomal markers in plasma (e.g. C29 and pipecolic acid). Conclusion: Relatively mild ZSDs with prolonged survival is not uncommon in ZSDs. In addition, mild patients can present with normal peroxisomal markers. 43 O65 -­‐ 1997 Hematopoietic stem cell transplantation in juvenile metachromatic leukodystrophy Groeschel S, Bley A, Kühl JS, Kehrer C, Müller I, Kohlschütter A, Weschke B, Krägeloh-­‐Mann I. Department of Pediatric Neurology & Developmental Medicine, University Children’s Hospital, Tübingen, Germany -­‐ [email protected]­‐tuebingen.de Objective: Hematopoietic stem cell transplantation (HSCT) is thought to result in endogenous and continuous enzyme replacement in metachromatic leukodystrophy (MLD), a rare neurometabolic disorder. Former anecdotal HSCT reports indicated inconclusive results due to the variable natural course of later onset forms. Patients and methods: 23 patients with juvenile MLD had undergone HSCT in 3 German centers between 1991 and 2011. Their motor and cognitive functions as well as MRI changes were compared to 25 untreated MLD patients. ‘Stable disease’ was defined as losing not more than one level in gross motor function (GMFC-­‐MLD) and less than 15 IQ points (1 SD). Results: Among HSCT patients, 4 children died from transplant-­‐related mortality; two patients with rapid MLD progression at HSCT deceased after 1.5 and 8.6 years. Although survival rates after HSCT did not differ from the non-­‐treated group, neurological outcome was improved. Patients transplanted in the presymptomatic and early symptomatic stage were more likely to show ‘stable disease’ (not significant, p=0.1, chi square). MRI severity scores at HSCT were significantly lower in patients with ‘stable disease’ than in those who deteriorated (p=0.007, M-­‐W-­‐test). In comparison to untreated controls, HSCT patients with ‘stable disease’ had lower MRI scores at their last exam (p=0.013, M-­‐W-­‐test). More importantly, 65% of untreated patients progressed to GMFC-­‐MLD level 5 (only head control possible) 10 years after disease onset, whereas all of the HSCT patients with ‘stable disease’ retained the ability to sit independently (level 3 or better) (p=0.025, log-­‐rank test). Conclusions: Children with juvenile MLD have a reasonable chance to show ‘stable disease’ after HSCT when transplanted at an early stage with limited MRI changes. These patients have a better motor outcome and MRI scores compared to untreated patients. However, benefit and risk have to be carefully balanced considering the relevant transplant-­‐related mortality. O66 -­‐ 1608 Hypomyelination and congenital cataract: three additional patients carrying novel mutations Biancheri R, Traverso M, Rossi A, Gazzerro E, Assereto S, Baldassari S, Fruscione F, Abdalla EM, Fassad MR, Ruffinazzi G, Savasta S, Zara F, Minetti C. Department of Neuroscience, Istituto Giannina Gaslini, Genova, Italy -­‐ [email protected] Objectives: to describe three additional patients affected by Hypomyelination and congenital cataract (HCC, OMIM #610532) carrying novel mutations in the FAM126A gene. HCC is a rare autosomal recessive disorder characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system (Zara F et al, 2006; Biancheri R et al, 2007). Materials and methods: a 19-­‐month-­‐
old girl from Morocco (patient#1) and two female siblings aged 7 and 4 years respectively from Egypt (patients #2 and #3) underwent clinical, neurophysiological, neuroradiologic and molecular studies. Results: Patient#1 showed bilateral congenital cataract and mild developmental delay. Nerve conduction velocity studies were normal. Brain MRI showed diffuse supratentorial hypomyelination. Molecular analysis identified the homozygous variant c.169T>C determining the substitution of cysteine with arginine in position 57 of the protein. Patients #2 and #3 showed congenital cataract and developmental delay, being unable to walk without support. Pyramidal and cerebellar signs were evident at neurological examination and peripheral nervous system involvement was depicted by neurophysiological studies. Brain MRI showed diffuse supratentorial hypomyelination with superimposed areas of increased water content. Molecular analysis identified a microdeletion c.100-­‐101delAA which causing a premature stop (p.Lys33Glufs*17) in the protein. Conclusions: The clinical picture of the first patient is consistent with a mild form of HCC. Interestingly, this is the second patient in whom peripheral nervous system was not involved. It is likely that the identified missense mutation has less detrimental effects if compared with splice-­‐site mutations or deletions. On the other hand, the phenotype of the siblings is consistent with the classical HCC form. This report further confirms that HCC is not uncommon in the Mediterranean area. The peculiar clinical and magnetic resonance findings are useful to properly address molecular investigations to obtain the correct diagnosis. O67 -­‐ 2165 Phenotypical variation in vanishing white matter disease van der Lei HDW, Gerver JAM, van Berkel CGM, van der Knaap MS. Child Neurology, VU University Medical Center, Amsterdam the Netherlands -­‐ [email protected] 44 Objective: Vanishing white matter (VWM) is an autosomal-­‐recessive leukoencephalopathy characterized by slowly progressive ataxia and spasticity with additional stress-­‐provoked episodes of rapid deterioration. VWM is caused by mutations in the genes encoding eukaryotic initiation factor 2B, which is pivotal in protein translation. The disease onset, clinical severity and disease course of VWM patients vary greatly. Although VWM was initially recognized as a disorder of young children, it has become clear that the variation in disease severity is large. Severe forms start in the antenatal or early infantile period and lead to early demise. Much milder variants start in adolescence or adulthood and are characterized by slow disease progression. Large studies on phenotypical variation are scrace. Methods: We performed a large cross-­‐sectional observational study and included all available patients from our genetically confirmed VWM patient database. We used clinical questionnaires on rubust parameters to collect information on disease course. Results: From our database of 228 patients with VWM, 5 patients were excluded because of co-­‐morbidity. 102 patients were female. Mean age of first symptoms was 7.5 years (range 0-­‐54.0). Mean age at diagnosis was 14.4 years (range 0-­‐59.3). Mean age of death (54 patients) was 9.1 years (range 0.1-­‐39). We divided the population into four age of onset categories; antenatal-­‐
infantile (0-­‐≤2 years), early-­‐juvenile (2-­‐≤6 years), late-­‐juvenile (6-­‐≤18 years), and adult onset (>18 years). Young patients had a more severe disease course characterized with earlier fatality, loss of independent walking, vision and speech, more involvement of other organs, epilepsy, and higher occurrence of coma episodes. The younger the more sensitive to stress. Female patients were older and had milder disease. Conclusions: The clinical variation in VWM is extremely wide. The younger the first neurological symptoms appear, the more severe the disease course is. Females tend to have less severe disease. O68 -­‐ 2091 Neurological phenotypes in Niemann-­‐Pick type C disease: unraveling an overlooked neurometabolic disorder Lourenço CM, Van der Linden V, Bonfim D, Ribeiro E, Marques Jr W. University of Sao Paulo, Sao Paulo, Brazil -­‐ [email protected] Objective: Niemann-­‐Pick type C disease (NP-­‐C) is a rare inborn error of metabolism caused by defective intracellular transport of cholesterol. It can present with a wide range of neurologic findings, some of them quite non-­‐specific. This study discusses the neurological features of NP-­‐C. Design: Retrospective cohort study. Method: A retrospective study, with review of neuroimaging and neurophysiological data, was carried out of Brazilian NP-­‐
C patients diagnosed in the last 6 years. Results: Thirty-­‐eight patients were included in the study, in 25/38 NP-­‐C was confirmed by filipin staining (13 patients required molecular analysis). The following clinical types were seen seen: perinatal (5), infantile (15) and juvenile (18). Prolonged neonatal jaundice was a common feature and 3 patients were diagnosed with “neonatal hepatitis”. Patients with the perinatal form usually had hypotonia as the main feature, followed later by spasticity. Infantile patients usually had a “symptom-­‐free” period, followed by relentless neurodegeneration: cerebellar ataxia, dystonia, learning disabilities and behavior changes were commonly seen in this group. Juvenile patients, presented mostly with progressive psychiatric changes and extrapyramidal features. Ocular abnormalities were seen in 30 patients (mostly, vertical supranuclear gaze paralysis). Leukoencephalopathy and progressive cerebral/cerebellar atrophy were the main MRI features. Gelastic cataplexy, although present only in a subset of the infantile/juvenile patients, is a relatively specific finding for NP-­‐C. Conclusion: Neurological manifestations in NP-­‐C patients are extremely variable, even in the same family. Better understanding of the natural history of the disease is crucial for evaluation of potential therapeutic approaches in such devastating disorder. O69 -­‐ 1973 MRI in the diagnosis of peroxisomal disorders when laboratory tests fail van der Knaap MS, Ferdinandusse S, Vanderver A. Child Neurology, VU University Medical Center, Amsterdam -­‐ [email protected] Objectives: Peroxisomal blood tests are generally considered to be conclusive. We observed several patients with a clinical and MRI phenotype suggestive of a peroxisomal defect, but no convincing abnormalities in peroxisomal blood tests. Brain MRI showed typical abnormalities as observed in different variants of peroxisomal disorders. Our aim was to evaluate the accuracy of this MRI diagnosis with further peroxisomal and molecular testing. Materials and Methods: We searched our database of unclassified leukoencephalopathies and found 18 such patients. We collected clinical data and scored available MRIs of these patients. We performed further peroxisomal studies in fibroblasts, including immunofluorescence microscopy analysis with antibodies against catalase, a peroxisomal matrix enzyme. We performed complementation analysis. We analyzed the suspected genes. Results: We confirmed the diagnosis of Zellweger spectrum disorder in 3 patients, D-­‐ bifunctional protein deficiency in 3 patients, and Refsum disease in the others. The clinical findings were within the spectrum known 45 for these diagnoses. In the early onset peroxisomal disorders, sequential MRIs showed that the abnormalities started in the hilus of the dentate nucleus and superior cerebellar peduncles. Subsequently, the cerebellar white matter and brain stem tracts were affected, followed by the parieto-­‐occipital white matter, splenium of the corpus callosum and posterior limb of the internal capsule. Eventually, all cerebral white matter became abnormal. The thalamus was typically affected as well. In patients with Refsum disease the cerebellar white matter was affected. Conclusions: If MRI reveals abnormalities suggestive of peroxisomal defects, negative peroxisomal blood tests do not exclude the diagnosis. DNA analysis of suspected genes or further tests in fibroblasts should be performed, most importantly immunofluorescence microscopy analysis with antibodies against catalase to stain peroxisomes. O70 -­‐ 1720 Brain Volumetry and Clinical Scoring in Patients with CLN2 Disease: A Diagnostic Tool to Monitor Disease Progression Löbel U, Nickel M, Nestrasil I, Sedlacik J, Kohlschütter A, Schulz A. Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-­‐Eppendorf, Hamburg, Germany -­‐ [email protected] Objectives Brain atrophy due to neuronal loss is a striking feature of patients with late-­‐infantile neuronal ceroid lipofuscinosis (CLN2), one of the most common degenerative brain disorders in childhood. A precise and quantitative description of disease progression is urgently needed in order to establish an evaluation tool for future experimental treatments. We measured the longitudinal development of gray matter (GM), white matter (WM) and CSF volumes and correlated those with the clinical course. Materials and Methods Twenty-­‐one MRIs of eight patients (3 male; 5 female; mean age, 6.9 ± 2.5 years) with genetically confirmed CLN2 were performed on a 1.5T scanner using a 3D T1-­‐weighted magnetization-­‐prepared rapid gradient-­‐echo (MP-­‐RAGE) sequence using the following parameters: TR/TE/TI/flip angle= 1900/2.97/1100ms/15°; FOV, 256 mm; matrix, 256×176; slice thickness, 1 mm; 160 slices with whole brain coverage. Volumetric segmentation of the brain was performed with the Freesurfer image analysis suite. The clinical severity was assessed by the Hamburg late-­‐
infantile NCL-­‐score, a disease-­‐specific scoring system. Results The volumes of overall supratentorial brain tissue, supratentorial cortical GM, volume of basal ganglia and thalami, cerebellar GM and cerbellar WM significantly decreased with age (P<.01), while the volume of the lateral ventricles increased (P=.03). Supratentorial WM volume did not correlate with age. A strong correlation with clinical scoring existed for all GM regions (P<.01) and for CSF volume (P=.011). Conclusions Patients with CLN2 showed a highly homogeneous decline of GM and WM, and an increase of CSF volumes. The correlation of MRI parameters with age and the clinical score was stronger for the GM volumes as for CSF volumes. Decline of cortical GM volume seems to be the most sensitive parameter for assessment of disease progression and represents a potential sensitive outcome measure for evaluation of future therapies. O71 -­‐ 2078 Brain gene therapy for Metachromatic Leukodystrophy Sevin C, Roujeau T, Piguet F, Sondhi D, Colle MA, Raoul S, Deschamps JY, Bouquet C. Inserm U986 Paris, Hopital Bictere, France -­‐ [email protected] inserm.fr Metachromatic Leukodystrophy (MLD) is a lethal neurodegenerative disease caused by deficiency of Arylsulfatase A (ARSA). The most severe late-­‐infantile form starts around 1-­‐2 years, leading to death within a few years, without available treatment. Among potential therapeutic interventions, brain gene therapy could ensure rapid and sustained delivery of ARSA enzyme in the brain, a prerequisite to arrest the neurodegenerative process in due time. We have demonstrated efficiency and safety of intracerebral delivery of adeno-­‐associated-­‐vector serotype rh.10 encoding human ARSA (AAVrh.10/ARSA) in MLD mice. Particularly, sulfatide isoforms that accumulate specifically in oligodendrocytes of MLD mice were normalized after treatment. We have optimized and validated, in non-­‐human primates, the neurosurgical procedure to allow simultaneous infusion of vector at 12 different brain sites, and demonstrated that the injection of AAVrh.10/ARSA (10EXP11 viral particles/hemisphere) results in significant ARSA overexpression in normal monkey, without any side effect. Toxicological studies have been achieved and we have obtained authorizations from regulatory agencies to move towards phase I/II tolerance and efficiency clinical trial that is opened for recruitment. This trial will enroll five children (age between 6 months and 4 years) with early-­‐onset forms of MLD, following specific clinical, neurocognitive and radiological criteria. AAVrh.10/ARSA vector will be administrated to 12 locations in the CNS, guided by brain imaging. Safety and efficiency parameters will be evaluated up to 2 years, a period that will be sufficient enough to assess the potential therapeutic efficiency of brain gene therapy in rapidly progressing forms of MLD. 46 Parallel session 12: Fetal and neonatal neurology Chairs: Marc D’Hooghe and Linda De Vries O72 -­‐ 1702 Concordance between Head Circumference Growth and Neurological Impairment among four Clinical Presentations of Microcephaly Coronado R, Giraldo J, Macaya A, Roig M. Hospital de Terrassa, Catalonia, Spain -­‐ [email protected] Our aim was to investigate correlations between head circumference (HC) growth and neurological impairment among four different clinical presentations of microcephaly in pediatric patients. HC charts of 3,269 patients from a tertiary paediatric neurology section were reviewed and 136 microcephalic participants were selected. Standardized HC Minimum, HC Drop and HC Catch-­‐up variables were defined. Children with evidence of Severe Learning Disability (IQ below 70) and/or significant Cerebral Palsy (GMF-­‐CS III or higher) were classified within the Neurologically Impaired Group and the rest of participants within the Normal-­‐Mildly Impaired Group. Using the Head Growth Function C= HC Minimum + HC Drop, with a cut-­‐off level of C = –4.28 SD, we analyzed the agreement between the function prediction and the actual neurological status in four clinical groups: Idiopathic, Familial, Syndromic and Symptomatic. We discuss the differences found in the concordance between function prediction and neurological outcome for every clinical presentation of microcephaly. Our results are helpful to refine the clinical use of HC charts in order to anticipate Neurological Impairment in microcephalic infants and children. O73 -­‐ 1935 SBA and Control Muscle Ultrasound Density From Pre-­‐ to Postnatal Life Verbeek RJ, Sollie KM, Mulder PB, van der Hoeven JH, Hoving EW, Sentner CP, Sival DA. Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands -­‐ [email protected] Objectives: In spina bifida aperta (SBA), the “second-­‐hit of damage” refers to delayed neurological damage superimposed upon the congenital myelomeningocele (MMC). Neuro-­‐protective treatment strategies aim to reduce this, but potential neuromuscular gain is still unclear, partly by the lack of comparable quantitative indicators. We reasoned that longitudinal muscle ultrasound density (MUD) could non-­‐invasively elucidate alterations in segmental neuromuscular integrity. However, longitudinal fetal MUD outcomes are still unknown, so far. In SBA and control children, we aimed to assess and compare MUD from pre-­‐ to postnatal life. Materials and methods: In 30 SBA [MMC Th8-­‐S1 (median L4)] and 20 control children we cross-­‐sectionally compared MUD of biceps, quadriceps, tibial anterior and calf muscles during the 1st; 2nd and 3rd trimester of pregnancy and subsequently during 0, 6 and 12 months postnatal age. Results: 12 of 30 SBA-­‐patients died (9 fetuses by planned terminated pregnancy; 3 neonates by the consequences of devastating hydrocephalus). Both SBA and control children revealed an intra-­‐individual MUD increase from the first trimester of pregnancy until the sixth month after birth [median MUD increase: 51% and 31% in SBA and controls, resp.] and stabilized, thereafter. Comparing fetal-­‐MUD between SBA and controls, revealed significantly higher SBA-­‐MUD outcomes from the 1st to 3rd trimester of pregnancy (caudal to the MMC; p<.05). Comparing postnatal-­‐MUD between SBA and controls, also revealed significantly higher SBA-­‐MUD outcomes from birth to 1 year (caudal to the MMC; p<.05). Conclusions: From the first trimester of pregnancy to 1 year of follow-­‐up, SBA MUD caudal to the MMC is increased compared to controls. This may implicate that the muscle ultrasound technique is applicable for longitudinal comparison between innovative fetal treatment strategies. Future analysis of individual MUD trajectories may reveal whether the technique could also be applied for individual neuromuscular surveillance. O74 -­‐ 2025 Benefits of universal newborn screening for permanent childhood hearing impairment to reading comprehension in adolescence: early confirmation of deafness matters Kennedy CR, Pimperton H, Chorozoglou M, Kreppner J, Mahon H, Powers SG, Peacock J, Stevenson JE, Terlektsi M, Worsfold SM, Yuen HM. Southampton General Hospital, Southhampton, UK -­‐ [email protected] Objectives: To determine the effect of universal newborn hearing screening (UNHS) and early confirmation of permanent childhood hearing impairment (PCHI) on reading and language in adolescence. Materials and methods: Long-­‐term follow-­‐up study of a large group of deaf teenagers and a comparison group of normally hearing children all of whom were previously involved in population-­‐based studies of UNHS when they were born in 1992-­‐97 and also had assessment of language and reading at primary school age.1,2 The primary outcome was scores on the York Assessment of Reading for Comprehension (YARC) analysed in a regression 47 model that adjusted for the effects of maternal education, non-­‐verbal ability (Raven’s progressive matrices score) and severity of PCHI. Language comprehension and expression were also assessed. Scores were expressed as z scores where the mean (SD) score in the comparison group was 0 (1). Results: Reading comprehension z-­‐
scores at mean (SD) age of 17.1 (1.45) years in 67 of 98 (68%) of those previously assessed at primary school age, including 15 with cochlear implantation, were significantly higher in those whose PCHI had been confirmed at age < 9 months than in those with later confirmed PCHI (group means -­‐ 0.63, -­‐1.86 respectively; adjusted group mean difference = 1.07, 95% CI = 0.33 to 1.81, p = 0.005). This pattern of findings was attributable to the subgroup treated with hearing aids and was not seen for the subgroup who had received cochlear implants. Language outcomes showed similar patterns of inter-­‐group differences. Conclusions: This unique study shows continuation of benefit into adolescence in aided children with bilateral PCHI from confirmation of deafness prior to age 9 months. Other factors seem more salient in determining the reading and language outcomes of cochlear implantees. O75 -­‐ 1987 Specific impairment of functional connectivity between language regions in former early preterms Wilke M, Hauser T-­‐K, Krägeloh-­‐Mann I, Lidzba K. Department of Pediatric Neurology & Developmental Medicine, University Children’s Hospital Tübingen, Germany -­‐ [email protected]­‐tuebingen.de Objectives: Prematurity is associated with a high risk for an adverse neurodevelopmental outcome; particularly in children born ≤ 32 weeks of gestation. In recent years, the importance of neurocognitive deficits has been increasingly recognized. Among these, language has consistently been shown to be affected. It has the advantage that it can be well-­‐characterized using both neuropsychological testing and non-­‐invasive imaging approaches, such as functional magnetic resonance imaging (fMRI). Materials and Methods: We here report on a study comparing former early preterm born children and adolescents (PT, n = 29, 20M) and typically developing children (TD, n = 19, 7M), using conventional MRI group analyses as well as task-­‐based and resting-­‐state functional connectivity analyses. Results: We found only small regions with significantly different activation on the group level (PT > TD) but significantly stronger connectivity between functionally-­‐defined superior temporal lobe (STL) language regions in TD participants. There were also significant differences in local and global network efficiency (TD > PT). Surprisingly, there was a stronger connectivity of STL regions with non-­‐STL regions both intra-­‐ and interhemispherically in PT participants, suggesting the presence of both reduced and increased connectivity in the language network of former preterms. Very similar results were obtained when using task-­‐
based vs. resting state functional connectivity approaches. Finally, lateralization of functional connectivity correlated with verbal comprehension abilities, suggesting that a more bilateral language comprehension representation in the brain is associated with better performance. Conclusions: Our results suggest the existence and persistence of abnormal connectivity patterns; they are discussed in the context of normal brain and language development. They underline the importance of interhemispheric crosstalk for the development of language comprehension in former early preterms. O76 -­‐ 1901 Neurodevelopmental outcomes of newborns requiring a brain MRI: A retrospective study Papandreou A, Poulton C, Kermode R, Ramesh CA. West Hertfrodshire Hospitals NHS Trust, Watford General Hospital, Watford, UK -­‐ [email protected] Objectives: To assess neurodevelopment of babies requiring an MRI brain in the neonatal period. Materials and methods : A retrospective study was performed. All neonates (n=84), born in a UK district general hospital and requiring an MRI brain from January 2001 to December 2009 were included. Neurodevelopmental status around the age of 2 years was assessed, either in a tertiary centre (using the Griffiths developmental assessment tool) or locally by community and/or acute paediatric consultants. Babies lost to follow up before the corrected age of 12 months were not included in our results analysis. Results: 70/84 notes were reviewed. 74% had a final neurodevelopmental assessment at a corrected age equal or greater than 18months. 14%(n=10/70) were lost to follow up before 12months corrected age. Neurodevelopmental outcomes were correlated with clinical examination at discharge, with imaging and EEG findings. 16% of patients with normal examination at discharge had moderate/severe delay. Conversely, 73% patients with abnormal neurological examination had developmental delay (18% mild, 55% moderate/severe) during final assessment. 28% of patients with abnormal cranial ultrasound scans had mild delay and 28% had moderate/severe delay. A normal MRI brain was associated with normal neurodevelopment in 100% of cases. An abnormal MRI was associated with mild delay in 30% and moderate/severe delay in 30% of cases. An abnormal neonatal EEG was associated with 50% moderate/severe developmental delay. An abnormal MRI paired with an abnormal EEG report was associated with moderate/severe delay in 60% of patients. Conclusions: Neurological condition at discharge correlates well with 48 final outcomes. Cranial ultrasound abnormalities do not necessarily predict developmental delay. A normal MRI is a very strong predictor of normal neurodevelopment. An abnormal MRI is associated with moderate to severe delay in 30% of cases, percentage which is increased to 60% when paired with an abnormal EEG. O77 -­‐ 1605 Thrombophilic genes polymorphisms in children with perinatal brain injury Baranov DA, Lvova OA, Kuznetsov NN, Kovtun OP, Plaxina AN, Kolmogortseva VD. City’s Perinatal Center, Russia -­‐ [email protected] Aim. To estimate the role of inherited thrombophilia in newborns with hypoxic-­‐ ischemic encephalopathy (HIE) and intraventricular hemorrhage (IVH). Materials and Methods. A double center case-­‐control study. We screened 49 full-­‐term and preterm infants with HIE/IVH and 57 term-­‐ and sex matched healthy control group for 7 single nucleotide polymorphisms (SNPs) of hemostasis’ and folic acid cycle’s enzymes’ genes with the help of polymerase real-­‐time chain reaction. Results. Almost all the neonates had the thrombophilic SNPs in homozygous or heterozygous state 2,76+/-­‐1,0 vs 1,88+/-­‐0,8. Only 2 infants (control group) had no gene’s defects. One SNP had been identified in 6vs18 cases (p=0,01), two – 13 vs22 (p=0,1), three – 18vs15 (p=0,1), four (n=11) and five (n=1) SNPs had only neonates with HIE/ IVH (p=0,001). 16 patients had FGB:G-­‐455A polymorphism versus 7 in control group (OR=3,46, 95% confidence interval (CI) 1,3-­‐9,5; p=0,01). Prothrombin gene heterozygosity in normal controls (1.8%) did not statistically differ from HIE/ IVH cases (6.1%) (p=0,2). We also observed F5: G1691A 5 vs0 (p=0,018); ITGA2: C807T 29vs23 (OR=2,14, 95% CI 1,0-­‐4,7; p=0,04); ITGA2: TT in homozygous state 8vs0 (p=0,001); ITGB: T1565C 20 vs.16 (OR=2,19, 95% CI 1,0-­‐4,9; p=0,01); PAI-­‐1: -­‐675 4G4G in homozygous state 15vs6 (OR=3,75, 95% CI 1,3-­‐10,9; p=0,009); MTHFR: C677T 25vs17 (OR=2,45, 95% CI 1,1-­‐5,5; p=0,02). Conclusion. The incident of severe thrombophilic SNPs (FGB: G-­‐455A, F5: G1691A, ITGA2: C807T, ITGB: T1565C, MTHFR: C677T) among neonates with HIE/ IVH is higher than in control group. The carrier state of these SNPs increases the chance to develop perinatal HIE/IVH twice and more. O78 -­‐ 1870 Neuro-­‐imaging and Neurodevelopmental outcome in Preterm infants with a Periventricular Haemorrhagic Infarction located in the Temporal and Frontal lobe Soltirovska Salamon A, Groenendaal F, Van Haastert IC, Rademaker CM, Benders MJ, Koopman-­‐Esseboom C, de Vries L. Department of Neonatology, Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, The Netherlands -­‐ [email protected] Objectives: The neurodevelopmental outcome of preterm infants with periventricular haemorrhagic infarction (PVHI) has overall been reported as poor. The spatial relationship between the site of the PVHI and the corticospinal tracts is important for predicting motor outcome. No studies have compared the outcomes of infants with PVHI located in the temporal or frontal lobe. The aim of this study was to compare clinical, neuroimaging characteristics and neurodevelopmental outcome in preterm infants with a PVHI located in the temporal and frontal periventricular white matter. Methods: retrospective hospital based study of preterm infants with a gestational age < 34 weeks with a frontal (n=22) and temporal (n=12) PVHI. The clinical course, neuroimaging studies (cranial ultrasound and/or MRI) and neurodevelopmental outcomes were reviewed. Adverse outcome was defined as moderately or severely abnormal neurological examination during the last visit, presence of cerebral palsy, epilepsy, hearing or visual impairment and/or an abnormal development between 24 and 36 months (Griffiths' developmental quotient ≤ 85). Results: infants with a temporal PVHI were significantly more at risk of an adverse outcome compared with those with a frontal PVHI (p 0.006). One infant with a temporal lobe PHVI developed ipsilateral CP due to a parietal PVHI on the contralateral side. Cognitive impairment was noted in one third of the infants in both groups. A significantly larger proportion of infants with a temporal PVHI developed visual impairment and/or behavioural problems (50% and 70% respectively) compared to those with a frontal PVHI (9% and 13% respectively). Conclusion: PVHI located in the temporal and frontal lobe is almost invariably related to a normal motor outcome, but carries a risk for cognitive, behavioural and visual problems. Preterm infants with temporal lobe PVHI are more at risk of an adverse outcome than those with frontal lobe PVHI. O79 -­‐ 1599 Prognostic value of conventional EEG in asphyxiated term newborns treated with Hypothermia: experience in 20 cases Aeby A, Khabbache K, Van Overmeire B, Vermeylen D, Van Bogaert P. Pediatric Neurology, Erasme-­‐Hospital-­‐ULB. [email protected] 49 Introduction: Perinatal hypoxic ischemic encephalopathy (HIE) is an important cause of mortality and neurologic morbidity in the term newborn. Hypothermia has shown to reduce death and neurologic impairment in several studies on HIE infants. Numerous studies have shown that conventional EEG performed at 24 h of life has a very robust prognostic value in HIE managed without hypothermia. Nevertheless, the prognostic value of conventional EEG in HIE treated with hypothermia is uncertain. Objectives: To identify the prognosis value of conventional EEG in the first 20 HIE newborns treated with hypothermia at Erasme Hospital Methods: We reviewed the medical records, MRI, electroencephalograms and outcome data of the twenty HIE newborns that were managed with hypothermia in our service between 2008 and 2012. Bad neurological outcome was defined as Bayley III score < 70 at 2 years or cerebral palsy or moderate (parasagittal brain injury) to severe (basal ganglia lesions) brain injury on early (day 4) brain MRI. EEG was graded according to Murray classification (Grade 0 to 4). Results: Eight infants died (40%), amongst which two had a brain MRI that revealed severe brain injury. Amongst the 12 survivors, 11 had a normal neurological examination or Bayley III score and one had a cerebral palsy. All had a brain MRI, which was normal or mildly abnormal in eleven patient and moderately abnormal in one patient. All twenty patients showed significant abnormalities in the first EEG (Murray score ≥1). Death or bad neurological outcome was associated with the persistence of Murray score ≥ 2 at 48 hours. A normalization of the EEG (Grade 0-­‐1) in the first 48 hours was always associated with a good prognosis. Conclusions: Our study shows that conventional EEG performed at 48 hours in newborns with HIE undergoing therapeutic hypothermia provides prognostic information about neurologic outcome. O80 -­‐ 1570 Cognitive outcome in childhood following unilateral perinatal brain injury van der Aa NE, lvan Buuren LM, Dekker HC, Vermeulen RJ, van Nieuwenhuizen O, van Schooneveld MMJ, de Vries LS. Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands -­‐ [email protected] Objectives: To assess cognitive outcome in children with periventricular haemorrhagic infarction (PVHI) or perinatal arterial ischemic stroke (PAIS) and relate these findings with early developmental outcome and neonatal MRI findings. Methods: A neuropsychological assessment was performed in 50 children with unilateral PVHI (n=21) or PAIS (n=29) at a median age of 11y 9mo (range 6-­‐20 years) and included tests for intelligence, verbal memory, visual-­‐motor integration, word comprehension, attention, reaction times and executive function. The Griffiths’ scales were used for early developmental assessment at 24 months (range 18-­‐32 months). Results: In children with PVHI, both the early Griffiths’ scores (mean 87, 95%CI 83-­‐92) and the Full Scale IQ (FSIQ) scores at school age (mean 86, 95%CI 78-­‐94) were below the test mean of 100. In the PAIS group, early Griffiths’ scores were within the normal range (mean 98, 95%CI 93-­‐104) but at school-­‐age FSIQ scores were below average (mean 87, 95%CI 80-­‐94). In children with PVHI, FSIQ scores correlated with the level of maternal education and were lower following ventricular dilatation, whereas involvement of basal ganglia and thalami and postneonatal epilepsy were associated with lower cognitive outcome in PAIS children. Conclusion: Cognitive outcome following PVHI or PAIS is below average, but still within one SD for most children. Prediction of cognitive outcome remains challenging, but some early predictors can be recognised. Parallel session 14: Learning disabilities, ADHD and autism Chairs: Patrick Berquin and Sergiusz Jozwiak O81 -­‐ 1871 Motor cortical inhibition in ADHD: modulation of the transcranial magnetic stimulation-­‐evoked N100 during a go/nogo task D’Agati E, Hoegl T, Dippel G, Curatolo P, Bender S, Kratz O, Moll GH, Heinrich H. University Hospital of Erlangen, Germany, Tor Vergata University, Rome, Italy -­‐ [email protected] Objectives: The N100 component, evoked by transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is associated with the activation of inhibitory cortical circuits and has recently been suggested as a potential marker of inhibition in Attention Deficit Hyperactivity Disorder (ADHD). In healthy subjects, the TMS-­‐evoked N100 decreases during motor response preparation and movement execution and increases during response inhibition. This study is the first investigating modulation of the TMS-­‐evoked N100 at stages of response preparation, activation, execution and inhibition in ADHD patients during a go/nogo task. The aim of the present study was to investigate the modulation of the TMS-­‐evoked N100 at stages. Materials and Methods: 18 children with ADHD and 19 typically developing children, aged 10 to 14 years, all right handed were 50 assessed. TMS was delivered over the left motor cortex, the TMS-­‐N100 was measured at electrode P3. The TMS-­‐
evoked N100 was determined at rest and at different time points (50 ms before S2; 150, 300 and 500 ms after S2) in a cued go/nogo task (S1-­‐S2 paradigm). Correlations between the TMS-­‐evoked N100 measures, MEP-­‐
related TMS measures (e.g., short-­‐interval intracortical inhibition) and performance measures were calculated. Results: Though the TMS-­‐evoked N100 was not found to be significantly reduced at rest in the ADHD group, a smaller increase in go trials and a smaller decrease after inhibiting a response compared to typically developing children were observed. In go trials, a lower TMS-­‐evoked N100 was associated with a smaller variability of reaction times. Conclusions: A reduced modulation of the TMS-­‐evoked N100 amplitude at response execution and inhibition during a go/nogo task, extends the picture of inhibition deficits at the cortical level in ADHD underlining the relevance of the TMS-­‐evoked N100. Findings suggest a functional involvement of the mechanisms underlying the TMS-­‐evoked N100 at the motor output stage. O82 -­‐ 1582 Preliminary data on the use of cigarettes, alcohol and drugs in a follow-­‐up study of adolescents with Tourette Syndrome Groth C, Debes N, Skov L. Pediatric Department, Herlev University Hospital, Denmark -­‐ [email protected] Background and aim: Tourette Syndrome (TS) and co-­‐morbid symptoms often have psychosocial and educational consequences for the young. Adolescents with inadequately treated TS are at risk of developing abuse of cigarettes, alcohol and drugs. This abuse stems from the belief that it may dampen the tics and co-­‐morbid symptoms. Here, we examined the use of cigarettes, alcohol and drugs in adolescents with TS and its correlation with severity of tics Methods: We included 116 adolescents with TS (age 16–20 years) and used structured interviews to assess the use of cigarettes, alcohol and drugs and the Yale Global Tic Severity Scale Score to assess the severity of the tics. Data from the Danish National Youth Health profile from 2011 were used as background population. Results: The mean age of the included TS adolescents was 18.43 years and 81% were male. Compared with data from the Danish National Youth Health profile, fewer TS adolescents used alcohol and fewer TS adolescents had a weekly alcohol consumption above 20 units. More TS adolescent were daily smokers of cigarettes (28.5%) than in the background population (16.2%). One fourth (27.3 %) of the TS cigarette smokers felt an effect of smoking on tic. Cannabis was more frequently smoked (within 4 weeks) by the TS adolescents (15.5%) than their national counterparts (6.2 %). Of the TS-­‐cohort 4.3% had abused one or more hard drugs previously. Smokers and frequent users of drugs had a tendency towards higher Global Tic Scores. Conclusion: Compared with the Danish background population, more TS adolescents are smokers of cigarettes and cannabis but fewer drink alcohol. Professionals need to be aware of the risk of abuse among TS adolescents. No clear correlation exists on the use of cigarettes, alcohol and drugs and the severity of tics. O83 -­‐ 2038 Do rolandic spikes on EEG at ADHD assessment influence on ADHD subtype and the use of methylphenidate for ADHD? Socanski D, Herigstad A. Stavanger University Hospital, Norway -­‐ [email protected] There are some relationships between attention-­‐deficit/hyperactivity disorder (ADHD) and rolandic spikes (RS) on EEG. RS occur in children with ADHD and may contribute to the occurrence of ADHD symptoms is some cases. Purpose: The aim of the present study was to investigate whether RS on EEG at ADHD assessment influence on the occurrence of ADHD subtype and the use of methylphenidate (MPH) for ADHD. Method: A retrospective study of 607 ADHD children (82.4%male), aged between 5-­‐14 years, who were diagnosed between January 2000 and December 2005 was performed. At least one routine awake EEG was recorded on 517 patients and 39 patients had EEG with epileptiform abnormalities (EA). The group with RS (group one) was compared to control groups; group two (patients with EA without RS) and group three (patients without EA). The three groups were followed-­‐up for one year. Measure outcomes were: ADHD subtype and the use of MPH for ADHD. Results: The group with RS consisted of 9 patients, 2 of them had previous history of epilepsy. Group two (patients with EA without RS), consisted of 30 patients, 10 of them had previous epilepsy. Of the 30 patients without EA (group three), nobody had previous epilepsy. ADHD combined subtype was diagnosed in the vast majority of cases in all groups. MPH was used similarly in groups (89 %, group one; 87 %, group two; 83%, group three). There was no statistic difference between groups with and without RS where MPH was used as medication for ADHD. The previous epilepsy co-­‐morbidity and occurrence of RSs were not a reason for not treating ADHD. Conclusions: The study suggested that RS occurrence at ADHD assessment does not influence on ADHD subtype occurrence and the use of MPH during 12 months follow-­‐up. 51 O84 -­‐ 1965 Improving Motor Learning in a Rat Model of ADHD Soderlund GBW, Bergquist F. Norway -­‐ [email protected] Introduction and objectives: Counterintuitively, acoustic white noise improves performance in inattentive persons, e.g. with ADHD. Such noise benefit may involve stochastic resonance, where a certain amount of noise improves suboptimal performance. The moderate brain arousal model predicts that low dopamine ADHD subjects require more noise than control subjects for optimal performance. Like people with AHDH, the spontaneously hypertensive (SH) rat displays hyperactivity, impaired attention and impaired motor skills. The effect of white acoustic noise and methylphenidate on motor learning and spontaneous motor activity was investigated in the SH rat. Methods: Charles River SH rats (SHR/NCrl) and Wistar (WIS/SCA) rats were trained in a skilled reaching task (Montoya) and a gross motor coordination task (Rotarod acceleration) for ten days. Spontaneous open field locomotor activity was recorded. The independent variables were: noise (75 dBA), silence (35-­‐40 dBA), methylphenidate (4 mg/kg i.p.), and vehicle (0.9% NaCl i.p.). Results: Noise but not methylphenidate, improved skilled reach learning in the SH rat. Learning was unaffected by treatments in Wistar rats. SH rats only performed at 50% of Wistar rat performance on the Rotarod but performance was improved to normal by both noise and methylphenidate. SH rats displayed open field hyperactivity, which was attenuated by methylphenidate but not by noise. Discussion: Auditory noise has a strong positive effect on skilled motor learning in the ADHD phenotype rat, but not in a control strain. The effect of noise differs in several important aspects from the effect of methylphenidate, indicating different action mechanisms that could be capitalized clinically. O85 -­‐ 1992 Cortico-­‐vocal coherence in autism spectrum disorders Suarez Garcia S, Clumeck C, Bourguignon M, Wens V, Op de Beeck M, Marty B, Soncarrieu M, Deconinck N, Delvenne V, Goldman S, Van Bogaert P, De Tiège X. Université Libre de Bruxelles, Laboratoire de Cartographie Fonctionnelle du Cerveau Belgium -­‐ [email protected] Introduction: The cortico-­‐vocal coherence (CVC) measures the coupling between the reader's voice and the listener's cortical activity. Significant coupling typically occurs at about 0.5 Hz between the time-­‐course of the reader's voice and listener's cortical neuromagnetic signals with local coherence maxima located at the right posterior superior temporal sulcus (pSTS) and gyrus. This phenomenon seems to reflect the processing of rhythmic prosody at the sentence level. The integrity of prosody perception is still a controversial question in autism spectrum disorder (ASD) population. Neuroimaging studies have pointed out the key role of the STS in the pathophysiology of ASD. We investigated, using magnetoencephalography (MEG), the CVC phenomenon in ASD Patients. Methods: Seven ASD patients (6 males and l female aged 13-­‐20 years), diagnosed with Asperger Syndrome (n=4) or Autism (n=3) based on DSM-­‐IV criteria and the Autism Diagnostic Observation Schedule (ADOS) were recruited. Cortical neuromagnetic signals were recorded using a whole-­‐scalp MEG while patients listened to a text continuously read by a French speaking male (live) and female (recording) during five minutes. In the life voice condition, the voice’s fundamental frequency was recorded by a three-­‐axis accelometer attached to the reader's throat. We recorded also cortical activity in a rest condition. Coherence, which is an extension of Pearson correlation coefficient, was computed between the reader's voice time-­‐course and listener's MEG signals. Coherent neural sources were subsequently reconstructed using Dynamic Imaging of Coherent Source. Results: Significant CVC was found in all patients in the two conditions with coherent sources located at the right STS (life voice) and at the right middle temporal gyrus (recorded voice). Conclusions: These results suggest the existence of preserved CVC in patients with ASD. This finding supports the existence of preserved neural processing of rhythmic prosody at the sentence level in ASD patients. O86 -­‐ 1830 Cognitive functions in school-­‐children with frontal or temporal epilepsy -­‐ the long term study Mazurkiewicz-­‐Beldzinska M, Kondracka J, Szmuda M, Matheisel A. Dept. of Developmental Neurology Medical University of Gdansk Poland -­‐ [email protected] Purpose:In order to compare the cognitive functions in school-­‐children with temporal (TLE) versus frontal lobe epilepsy (FLE) and control group from the time of diagnosis through the long term follow up the following study was performed. Method: 61 children with TLE 56 children with FLE and 60 healthysubjects were included in study. The applied test battery consisted of measures assessing both intelligence as well as executive and motor skills. All children had MRI and EEG recordings (usually in 3-­‐ 6 months intervals). The follow up took from 3-­‐ 7 years (mean 5,2 years). At the time of diagnosis and in 12-­‐ 15 months intervals the neuropsychological 52 assessment was done and the results were correlated with the number of seizures, treatment and EEG changes. Results: There was no significant difference in global IQ scores between the groups at the time of diagnosis. Later during the study we observed the lower IQ performance in FLE group with poor control of seizures. Children with FLE had significantly lower scores in nonverbal memory tasks, presented higher attention deficit and slower performance speed at the time of diagnosis and through the whole study. The TLE group performed significantly worse as compared with control group in verbal learning and performance speed with no differences in attention. That changed during the study where we observed negative effect on attention and aggravation in deficits in verbal and also in nonverbal memory tasks. Conclusion: The children with new onset FLE present with more severe cognitive and attention problems compared with TLE group, however the TLE group performance changed during time. The strong correlation between the focus localization but also type of treatment end seizure control was found and will be discussed. O87 -­‐ 1771 Long-­‐term simvastatin treatment for cognition and daily life in children with Neurofibromatosis type 1; results from the NF1-­‐SIMCODA trial van der Vaart T, Plasschaert E, Rietman AB, Renard M, Oostenbrink R, Vogels A, de Wit MC, Descheemaeker MJ, Vergouwe Y, Catsman-­‐Berrevoets CE, Legius E, Elgersma Y, Moll HA. Department of Neuroscience; Department of Paediatrics; ENCORE Expertise centre for Neurodevelopmental disorders, Erasmus MC, Rotterdam, The Netherlands -­‐ [email protected] Background: Neurofibromatosis type 1 (NF1) is a common single-­‐gene neurocognitive disorder characterized by neurocutaneous symptoms, lower IQ, internalizing behavioural problems and attention deficits. In Nf1-­‐mice, loss of neurofibromin increases RAS-­‐activity and reduces synaptic plasticity in the brain. Statin-­‐ induced HMG-­‐CoA-­‐
reductase inhibition by statins prevented RAS-­‐activation, restored plasticity, learning and attention in Nf1-­‐mice. Short-­‐term simvastatin administration to NF1 patients was inconclusive. A trial with longer treatment duration and use of clinically relevant outcome measures was needed. The NF1-­‐SIMCODA trial aims at detecting the effects of long-­‐term simvastatin on cognition and daily life in children with NF1. Methods: Individuals from the Netherlands and Belgium aged 8 – 15 years with genetically confirmed diagnosis of NF1, not using stimulant medication were eligible for this 12-­‐month randomized double-­‐blind placebo-­‐controlled clinical trial. Intervention consisted of 20-­‐40 mg/d simvastatin or placebo. Primary outcomes were IQ (Wechsler Intelligence Scales for Children-­‐III-­‐NL) and parent reports on internalizing behavioural problems and attention problems (Child Behavioural Checklist) after 12 months of treatment. Results: We randomised 84 participants between March 9, 2010 and March 6, 2012. Data acquisition has been completed in March 5, 2013. Median age of participants was 11.5 years (range 7.9 – 16.0) and average IQ at baseline was 83.3 (SD 15.6). Conclusions: The effect of simvastatin on IQ and behaviour in children with Neurofibromatosis type 1 will be presented at the European Paediatric Neurology Society congress in Brussels. (Trial identifier: trialregister.nl number, NTR2150). 088 -­‐ 1682 Effects of methylphenidate on functional networks activation in children with Attention Deficit Hyperactivity Disorder Berquin P, Querne L, Service de Fall S, Delignieres A, Simonnot A, Le Moing A-­‐G. Service de Neuropédiatrie & GRAMFC U1105, CHU Amiens France -­‐ [email protected]­‐picardie.fr Background: Many fMRI studies in ADHD had focused on frontal regions known to be a site of action of methylphenidate and be involved in executive, control and inhibitory functions. New approach shifts the focus from regional brain abnormalities to dysfunction in distributed network organization. The objective was to study how the methylphenidate modifies in children with ADHD the activations of functional networks during visuospatial processing. Methods: Eleven drug-­‐naive ADHD children and 11 typically developing (TD) children performed a flanker task during magnetic resonance imaging. The ADHD-­‐group was scanned twice, before initiation of methylphenidate and one month afterwards with methylphenidate (extended-­‐release formulation). The functional sequence consisted of successive conflict/unconflicting blocks. Brain activity for visuomotor conflict was imaged by contrasting hemodynamic activity during conflict versus unconflicting blocks. Results: Prior to methylphenidate, the ADH-­‐group showed bilateral activations in visual and dorsal-­‐attentional (only the posterior part) networks and in several regions of the default-­‐mode network. In contrast, the TD-­‐group showed bilateral activation in the fronto-­‐parietal network. With methylphenidate, activations in the ADHD-­‐group were reduced in both visual and default-­‐mode networks. Methylphenidate also initiated activations in the anterior part of the dorsal-­‐attentional network and in the right hemispheric part of the fronto-­‐parietal network. Conclusions: Our results suggest that ADHD children engaged different networks than TD children for performed visuomotor conflict. Hyperactivation of the visual, dorsal-­‐attentional and default-­‐ mode networks could be 53 compensatory mechanisms and/or be consecutive to a default of inhibitory control normally exerted by the fronto-­‐parietal network. Methylphenidate by improving partially the activation of the fronto-­‐parietal network may improve in turn inhibitory control on visual and default-­‐mode networks. The dorsal attentional network remained activated, suggesting that attentional networks compensate the incomplete activation of the fronto-­‐
parietal network. O89 -­‐ 1600 Language development at 2 years is correlated to brain microstructure in the left superior temporal gyrus at term equivalent age: a diffusion tensor imaging study Aeby A, De Tiège X, David P, Balériaux D, Van Overmeire B, Metens T, Van Bogaert P. Pediatric Neurology and Laboratoire de Cartographie Fonctionnelle du Cerveau UNI (Université Libre de Bruxelles -­‐ULB Neuroscience Institute) Erasme-­‐Hospital, Belgium -­‐ [email protected]b.ac.be This study aims at testing the hypothesis that neurodevelopmental abilities at age 2 years are related with local brain microstructure of preterm infants at term equivalent age. Forty-­‐one preterm infants underwent brain MRI with diffusion tensor imaging sequences to measure mean diffusivity (MD), fractional anisotropy (FA), longitudinal and transverse diffusivity (λ// and λ⊥) at term equivalent age. Neurodevelopment was assessed at 2 years corrected age using the Bayley III scale. A voxel-­‐based analysis approach, statistical parametric mapping (SPM8), was used to correlate changes of the Bayley III scores with the regional distribution of MD, FA, λ// and λ⊥. We found that language abilities are negatively correlated to MD, λ// and λ⊥ in the left superior temporal gyrus in preterm infants. These findings suggest that higher MD, λ// and λ⊥ values at term-­‐ equivalent age in the left superior temporal gyrus are associated with poorer language scores in later childhood. Consequently, it highlights the key role of the left superior temporal gyrus for the development of language abilities in children. Further studies are needed to assess on an individual basis and on the long term the prognostic value of brain DTI at term equivalent age for the development of language. Parallel session 15: Epilepsy Chairs: Sameer Zuberi and Oebele Brouwer O90 -­‐ 2157 Treatment of Electrical Status Epilepticus in Sleep (ESES): A systematic review and meta-­‐analysis Van den Munckhof B, Van Dee V, Liukkonen E, Sagi L, Loddenkemper T, Sánchez Fernández I, Braun KPJ, Jansen FE. Rudolf Magnus Institute of Neuroscience, Department of Paediatric Neurology, University Medical Center, Utrecht, The Netherlands -­‐ [email protected] Purpose: Epileptic encephalopathy with ESES is a rare pediatric epilepsy syndrome with significant aggravation of interictal epileptiform discharges in sleep and acquired impairment of cognition or behavior. The aim of treatment of ESES syndrome is to improve cognitive outcome. However, it is unknown which treatment is most effective. The aim of this meta-­‐analysis is to create an overview of the current evidence for different treatment regimens in children with ESES syndrome. Methods: A broad literature search using Pubmed and Embase was performed. Articles were selected if they contained original treatment data of patients with ESES syndrome. Authors were contacted to gain additional information. Individual patient-­‐ data were collected, coded and checked by a second investigator. Results: The literature search yielded 1663 articles. After excluding duplicates and applying in-­‐ and exclusion criteria 109 articles remained that described 727 treatments in 493 patients. Treatment with conventional anti-­‐epileptic drugs (AED, n = 335) caused any (i.e. cognitive or EEG) improvement in 50% of patients, cognitive improvement in 38% and EEG-­‐improvement in 43%. Benzodiazepines (n=133) caused any improvement in 71%, cognitive improvement in 50% and EEG improvement in 61%. Steroids yielded any improvement in 84%, cognitive improvement in 85% and EEG improvement in 78%. Surgery (n=62) resulted in any improvement in 89%, cognitive improvement in 84% and EEG improvement in 82%. A subgroup analysis of studies that included consecutively treated patients only (n=309) showed significantly lower treatment effectiveness for AED and benzodiazepines (any improvement in 17% and 55% respectively). Conclusion: This meta-­‐analysis suggests superior effectiveness of steroids and surgery in epileptic encephalopathy with ESES. However, most studies were small and retrospective. Furthermore, the substantially lower success rates in the subgroup-­‐ analysis of consecutively treated patients suggest an important publication bias. Our findings emphasize the urgent need for a randomized controlled trial in patients with ESES syndrome. 54 O91 -­‐ 1581 Compensatory visual system adaptations after hemispherectomy in children Koenraads Y, van der Linden DCP, van Schooneveld MMJ, Imhof SM, Porro GL, Braun KPJ. Department of Ophthalmology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands -­‐ [email protected] Objectives: Several case-­‐reports have suggested that an anomalous head posture (AHP) and exotropia on the side of the visual field (VF) defect may compensate for homonymous hemianopia. The aim of this study was to determine the prevalence of these compensatory mechanisms in children who underwent hemispherectomy. Materials and Methods: Patient files from all children who underwent hemispherectomy and had a postoperative ophthalmological examination in the UMC Utrecht up to October 2012 were retrospectively reviewed. The prevalence of the possible compensatory mechanisms (dynamic AHP and manifest or intermittent exotropia both directed towards the side of the VF defect) was determined. Subsequently, clinical characteristics were compared between patients who did, and those who did not develop compensatory adaptations. To account for the potential effect of insufficient follow-­‐up time, children with no adaptations reported were only included in the study if follow-­‐up duration was at least two years. Results: 45 children (21 ♂ and 24 ♀) underwent a hemispherectomy (22 right and 23 left) at a median age of 2,1 yr (range 0,2-­‐14,3 yr). Median ophthalmological follow-­‐up was 2,4 yr (range 0,1-­‐14,8 yr). AHP and exotropia on the side of the VF defect were found in 53% and 40% of children respectively. The latter occurred significantly more often in children who underwent right-­‐sided hemispherectomy. There was no significant difference in age at surgery, etiology of epilepsy, seizure freedom, developmental scale, fixation, visual acuity, spherical equivalent or optic disc between the groups. Conclusions: This study shows that functional adaptations to compensate for homonymous hemianopia – i.e. AHP and exotropia – both occur frequently after hemispherectomy in children. Dynamic head posturing and exotropia of the eye on the side of the VF defect may be part of a coping strategy to maximize the visual field. Surgical treatment of exotropia should then be avoided. O92 -­‐ 2108 The classification of epilepsies using the ILAE revised terminology and concepts for organization of seizures and epilepsies and ICD-­‐10 -­‐ challenges in clinical practice Iliescu C, Barca D, Budisteanu M, Burloiu C, Butoianu N, Minciu I, Motoescu C, Tarta-­‐Arsene O, Craiu D. „Carol Davila” University of Medicine, Department of Neurology, Pediatric Neurology, Neurosurgery, Psychiatry -­‐ Pediatric Neurology Clinic No.II, Bucharest; Al. Obregia Hospital, Bucha rest, Romania -­‐ [email protected] Objectives: Epilepsies classification is important in clinical practice but different systems are used in the same time and the results might be inaccurate. New concepts were proposed but controversies exist and misunderstanding of terms persist in publications. The aim is to present our results and challenges we faced in applying the ILAE revised terminology and concepts for organization of epilepsies and to compare these with the data obtained with ICD-­‐10, which is used in daily practice. Materials and Methods: we searched our Epilepsy Registry and selected the cases admitted with a new diagnosis of epilepsy from our pediatric neurology clinic, during 2 consecutive months. We grouped the patients according with WHO age groups: infants (< 1 year), children (1 – 9 years old) and adolescents (from 10 years until 17 years old -­‐ upper age limit for pediatric specialties in our country). We used the history, clinical and complementary data for classifying the epilepsies and the ICD-­‐10 codes from files. Results: 51 patients under 18 years old were included. A diagnosis of electroclinical syndrome was possible in 28 (55%). Cause was defined in 20 of all patients (39%), and was unknown in 31. All 15 patients with an electroclinical syndrome and cause unknown were in fact „idiopathic” if using present classification, and 16 patients (31%) were with unknown cause and undefined prognosis. ICD-­‐10 classification offered few useful data for clinical practice. Conclusions: the ILAE revised terminology and concepts for epilepsies organization is useful. Still some terms are unclear and misunderstandings possible. Age grouping being different among publications, we propose that a standardized organization to be used and upper limit for pediatric age to be unified in studies, for useful analysis. ICD should be in accordance with the new concepts for a more accurate analysis on a National and European level O93 -­‐ 2003 Different aspects in the evaluation of vagus nerve stimulation efficacy among children with therapy-­‐refractory epilepsy Orosz I, Buck E, Sperner J, Thyen U. Department of Neuropediatrics, Childrens’s Hospital, University of Lübeck, Germany -­‐ [email protected] 55 Objectives: Efficacy of vagus nerve stimulation (VNS) among children with therapy-­‐refractory epilepsy has been reported to be around 30-­‐40% in most studies, although clinical experience shows that there are more patients who profit from VNS. Our goal was to examine the impact of VNS therapy not only on seizure frequency, but also on different other and so far underreported factors in children with recalcitrant epilepsy. Materials and Methods: 75 children (mean age at VNS implantation 10.9 ± 4.9 years, range 2.3 -­‐ 21.8 years) with treatment-­‐
resistant epilepsy implanted with a VNS system at the University of Lübeck, Germany, during the last decade were retrospectively analyzed. Patients were followed up to 11.4 years after VNS system implantation. Data were retrieved from patient charts and seizure diaries. Response was defined as ≥50% seizure reduction after VNS. Results: One year after implantation, the rate of responders and seizure-­‐free patients was 29.3% and 4%, respectively. At most recent follow-­‐up (mean 3.7 years, range 1.0 – 11.4 years), this rate was 37.3% and 13.3%, respectively. Significantly higher number of responders was observed with VNS output currents between 1.75 mA and 2.25 mA. At the last recording, 56% of patients had positive magnet effects, i.e. disruption of seizures. However, among these children there were up to 71.4% non-­‐responders according to seizure frequency analyses. By assessment of quality of life, most evident variables that improved with VNS therapy were mood, vigilance, and concentration. The longest seizure-­‐free time (days per month) was significantly increased during the whole follow-­‐up period. There was a significant decrease in number of hospital admissions and a trend towards a reduced number of stati epileptici 10 years before and after VNS. Conclusions: This implies that VNS in epileptic children has a broad spectrum of favourable effects, not being confined to reduction of seizure frequency. O94 -­‐ 1758 Cardiac and respiratory autonomic dysfunction in childhood epilepsy Jansen K, Varon C, Van Huffel S, Lagae L. Pediatric neurology, University Hospitals Leuven, Belgium -­‐
[email protected] Objectives Epilepsy is a neurological condition characterized by recurrent seizures. Since the autonomic nervous system has an important representation in the brain, autonomic disturbances can be part of the disease. Acute cardiac and respiratory changes can be seen due to involvement of autonomic control centers in seizure activity. Heart rate variability is an excellent tool to provide insight in the functionality of the autonomic nervous system. Our aim is to investigate the effect of epilepsy on the central autonomic nervous system by measuring heart rate, respiration and heart rate variability. Methods Long-­‐term EEG was recorded in childhood epilepsy patients including autonomic parameters. Heart rate was measured in 80 focal and generalized seizures. Respiration was measured in 20 focal and generalized seizures. Interictally, heart rate variability was assessed in 13 patients with West syndrome and 17 refractory epilepsy patients and compared to control subjects. Respiration was measured in 10 patients with West syndrome, 10 with temporal lobe epilepsy and 10 with absence epilepsy and compared to controls. Results Ictal tachycardia was clear in patients with focal seizures, but not in generalized seizures. In temporal lobe seizures, lower breathing frequencies with risk of apnea were noted. Interictally, a depressed heart rate variability was seen with a significant reduction in vagal tone during slow wave sleep after a longer disease course in patients with refractory epilepsy and West syndrome. In patients with West syndrome but also in absence epilepsy, respiratory control was altered in between seizures, early after onset of the disease. Conclusions We were able to show that cardiac as well as respiratory autonomic changes are present in childhood epilepsy. Respiration is altered earlier in the course of the disease compared to the cardiovascular system. Heart rate variability can be used as a biomarker for chronic autonomic dysfunction in patients with epilepsy. O95 -­‐ 1739 Severe myoclonic epilepsy in infancy: clinical and neuropsychological analysis according to age at diagnosis of SMEI El M Kaddem B, Christiaens F, van Rijckevorsel F, Nassogne MC. Université catholique de Louvain, Cliniques universitaires Saint-­‐Luc, Bruxelles, Belgium -­‐ [email protected] Introduction: Severe myoclonic epilepsy of infancy (SMEI) is a rare epileptic encephalopathy characterized by drug-­‐resistant febrile and afebrile generalized or unilateral convulsive seizures. Cognitive deterioration becomes evident from the second year of life. Sodium channel SCN1A gene mutations have been found in 40-­‐70% of patient with typical SMEI. Objectives: Clinical follow-­‐up, neuropsychological outcomes, control of seizures and antiepileptic treatments between different groups were analysed according to age at diagnosis of SMEI. Materials and Methods: A retrospective study realised in patients with SMEI and positive mutations of SCN1A, at Hospital Saint Luc. Medical records of 19 patients were reviewed to collect information regarding general characteristics, age at onset, type and duration of seizures, status epilepticus, neuropsychological features, and 56 genetic analysis. Antiepileptic treatment before and after genetic confirmation of SMEI was also noted. Patients were categorized according to the age at diagnosis of SMEI into three groups: Group 1 (3 patients diagnosed between 24-­‐31 years old), Group 2 (8 patients diagnosed between 6-­‐18 years old) and Group 3 (8 patients diagnosed between 6 – 24 months). Results: Epilepsy characteristics do not differ among the different groups at its onset. Later seizure control was more difficult to obtain in Groups 1 and 2; Group 2 being the one with the greatest seizure frequency. Patients in Group 1 and 2 received at least 4-­‐6 antiepileptic drugs and most of them were treated by currently contraindicated drugs. 66% of patients in Group 1 and 25% of patients in Group 2 have severe cognitive impairment. Conclusions: Seizure control in SMEI is difficult and cognitive prognosis remains poor. It appears that antiepileptic treatment according to new international recommendations leads to a better epileptic and cognitive development. For this reason, a prompt clinical and genetic diagnosis is necessary to provide an adequate treatment. O96 -­‐ 1638 Electrical status epilepticus in sleep (ESES): etiology, clinical picture and course Aleksandrova I, Bojinova V, Dimova P; Clinic of Child Neurology, “St. Naum” University Hospital of Neurology and Psychiatry, Sofia, Bulgaria -­‐ [email protected] Objectives: To analyze the etiology, clinical manifestations and disease course in children with electrical status epilepticus in sleep (ESES). Materials and Methods: We retrospectively analyzed the data of 60 children with ESES treated from 2006 to 2012. Results: Thirty eight patients had an atypical evolution of idiopathic focal childhood epilepsy with 33 of them being long-­‐term followed up. The mean age of seizure onset was 5 years with a mean age of ESES manifestation of 7 years. Initially, almost all children had focal seizures with or without secondary generalization. At the time of ESES manifestation 44.7% experienced new seizure types (atonic, myoclonic or atypical absences); 63.2% had increase in seizure frequency; and 44.7% had either cognitive deterioration or behavioral problems. The clinical features in two patients were consistent with acquired anterior opercular syndrome. In one case the epilepsy had a very aggressive course evolving to CSWS-­‐related encephalopathy. Twenty two patients had symptomatic epilepsy due to: cortical malformation (n=4), ante-­‐ or perinatal ischemic lesions (n=12), tuberous sclerosis, angioma, congenital toxoplasmosis, meningoencephalitis, stroke and microdeletion syndrome (each in one case). The epilepsy onset in this group was at a younger age (mean 2 years). Twenty-­‐one children were long-­‐term followed up. Seizure remission was achieved in 24/33 idiopathic cases. Improvement, or normalization, of EEG was achieved in 13/33 (40%) of them, while 20/33 (60%) had relapsing ESES. The evolution in the symptomatic group was unfavorable – 19/21 (90.5%) had relapsing or persistent ESES, and 16/21 (76%) continued to have seizures. Conclusion: With regard to the seizures, the outcome of ESES in idiopathic cases is good, yet many patients remained with cognitive or behavioral impairment. Thus, early recognition and appropriate treatment is essential for the prognosis. The underlying etiology seems to have a major impact, since patients with symptomatic epilepsy have a worse outcome. O97 -­‐ 1635 Treatment of electrical status epilepticus in sleep (ESES): efficacy and unsolved questions Dimova P, Alexandrova I, Bojinova V. Clinic of Child Neurology, St. Naum University Hospital of Neurology and Psychiatry -­‐ [email protected] Objectives: To analyze the treatment and its efficacy in children with electrical status epilepticus in sleep (ESES). Materials and Methods: We retrospectively reviewed the data of 60 children with ESES treated from 2006 to 2012. Results: In our cohort patients with idiopathic focal epilepsy predominated (38 vs 22 children with symptomatic epilepsy). They showed a later epilepsy and ESES onset and more benign disease course. A permanent remission of seizures and improvement, or normalization, of ESES was achieved with the initial treatment in 39.4% (13/33) of the idiopathic group. Best results were seen on therapy with: 1) corticosteroids in combination with ethosuximide [ESM] (n=2), levetiracetam [LEV] (n=3), clonazepam [CZP] and LEV (n=1) or lamotrigine [LTG] (n=1); 2) LEV alone (n=3) or in combination with valproate [VPA] (n=1) and CZP (n=1); 3) Sulthiame [STM] (n=1). Twenty out of 33 patients (60.9%) showed relapsing ESES. Later in the disease course seizure remission was achieved in 11/20 patients by: 1) corticosteroids alone (n=2) or in combination with LEV (n=1), ESM (n=1), CZP (n=1), Nitrazepam (n=1); 2) LEV (n=3); 3) STM (n=1); 4) ESM (n=1). The patients with symptomatic epilepsy had more unfavorable evolution as 19/21 (90.5%) had persistent or relapsing ESES with only transient improvement with various therapeutic approaches, and only 5 children (24%) became seizure-­‐
free. Conclusion: ESES is characterized by a significant therapeutic refractoriness, especially in symptomatic epilepsies. The most effective anticonvulsants in our study are LEV, benzodiazepines, STM and ESM. Corticosteroids, however, show the most pronounced and long-­‐lasting effect, but only when used in appropriate 57 doses and for sufficient period of time considering the risk of serious side effects. Large prospective studies are needed to establish guidelines for the treatment strategy in ESES. O98 -­‐ 1979 Intravenous methylprednisolone for the treatment of infantile spasms Aburahma A, Al-­‐Sharqawi S. Jordan -­‐ [email protected] Purpose: this is a description of the clinical experience of utilizing intravenous (IV) pulse methylprednisolone for the treatment of infantile spasms. Methods: a retrospective study utilizing chart reviews of all patients who presented with infantile spasms and were treated with IV pulse methylprednisolone between July 2007 and April 2013. Patients were identified through identifying all patients with a hypsarrhythmia pattern on EEG during that period of time. Data was collected regarding clinical presentation of patients, EEG results, neuroimaging, laboratory findings, presumed underlying cause of the spasms, response to treatment with pulse methylprednisolone, and complications of therapy. Results: Twenty nine patients were identified. All patients with infantile spasms were treated with IV methylprednisolone as ACTH is not available in Jordan. As EEG was utilized for identification of infants, all showed a hypsarrhythmia pattern. Twenty two patients had an abnormal MRI, most commonly congenital brain malformations, followed by evidence of perinatal brain injury. All patients received IV pulse methylprednisolone therapy at a dose of 20-­‐30mg/kg/day for 5 days, followed by outpatient oral prednisone taper. Oral Ranitidine was given during steroid therapy. Twenty one patients showed complete cessation of the spasms during the hospital stay. Four patients showed reduction in severity and frequency of spasms. None of the patients had any serious adverse effects that necessitated cessation of therapy. Conclusion: IV methylprednisolone is an effective, safe, inexpensive, and easy to administer therapeutic option for infants with infantile spasms. More studies are required to evaluate this therapy in a controlled manner and to evaluate the long term outcome of these infants. 58 2. Selected POSTER PRESENTATIONS Wednesday 25 September 2013 PP1 Cerebral palsy, neonatology, stroke Neonatology Lars Palm PP1.0-­‐1848 The Reparative Effects of Neural Stem Cells in Neonatal Hypoxic Ischemic Injury are Not Influenced by Host Gender Ashwal S, Ghosh N, Turenius C, Dulcich M, Denham CM, Tone B, Hartman R, Snyder EY, Obenaus A. Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California, USA -­‐ [email protected] BACKGROUND: Gender is increasingly recognized as an important influence on brain development, disease susceptibility, and response to pharmacologic and rehabilitative treatments. In regenerative medicine, it remains entirely unknown whether there is an interaction between transplanted stem cells and host gender that might bias efficacy and safety in some patients but not others. METHODS: As proof-­‐of-­‐concept, we examined the role of recipient gender in a rat pup model of neonatal hypoxic-­‐ischemic injury (HII) treated with human neural stem cells (hNSCs). Into the cerebral ventricles of rats subjected to HII, we implanted female hNSCs, labeled with superparamagnetic iron-­‐oxide (SPIO) particles, and serially monitored HII evolution (by magnetic resonance imaging [MRI], histopathology, behavioral testing) and hNSC fate (migration, replication, viability). RESULTS: Recipient gender after hNSC implantation did not influence the volume or location of ischemic injury (1, 30, or 90d post-­‐implantation) or behavior (at 90d). SPIO labeling did not influence HII evolution. Independent of gender, hNSC implantation appeared to have its greatest benefit on mild and moderate rather than severe HII lesions. Lesion volumes in pups with mild/moderate injuries receiving hNSCs remained stable over the 90d observation period rather than increasing as is the natural history for such lesions. Treatment, however, did not prevent the gradual increase in lesion volume in pups with severe HII. CONCLUSIONS: Our results suggest that hNSC treatment would be equally safe and effective for male and female human newborns with mild-­‐to-­‐
moderate HII. PP1.1 -­‐1847 Hypothermia after rat pup hypoxia/ischemia: effects on cytokines, signaling molecules and core/penumbra volumes Yuan X, Ghosh N, McFadden B, Tone B, Tian HR, Snyder EY, Obenaus A, Ashwal S.Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, Californie, USA -­‐ [email protected] Objective: Hypothermia (HT) is standard of care for neonates with hypoxic ischemic injury (HII). Because of its modest effect, additional translational studies are needed to maximize neuroprotection, specifically when HT is combined with other treatments (e.g., stem cells). Methods: Unilateral HII (carotid occlusion, 8% O2,) was induced in 10d rat pups and followed by 24 hours of HT (30ºC; n=18) or normothermia (NT, 35ºC; n=15). MRI, neurological testing (righting reflex) and cytokine/signaling molecule profiles (Luminex/ELISA) were collected pre-­‐HII and at 0, 24, 48, 72 hrs post HII. Results: Compared to NT, HT pups had less weight loss (33.5%) at 24hr and faster righting reflexes (43%) at 0-­‐48hr post HII. Compared to NT, HT reduced MRI measures of HII including the rat pup severity score (64%) & HII volumes (total lesion, 69%; ischemic core, 79% & penumbra, 63%) between 0-­‐48hrs. HT reduced expression of inflammatory cytokines (interleukin-­‐1β, p<0.05). Interferon-­‐γ, tumor necrosis factor-­‐α and monocyte chemoattractant protein-­‐1 expression were lower in the HT than in the NT group (although not statistically significant) indicating less inflammation in the HT group. Stromal cell-­‐derived factor-­‐1α levels were not modified (p<0.81) suggesting that HT does not affect stem cell signaling molecules. Interestingly, at 72hrs post HII (48hrs post HT) there was an increase in cytokine levels that was associated with increased HII injury volumes and a reduced righting reflex, suggesting a rebound effect. Our data demonstrate that HT reduces inflammatory cytokines without altering stem cell signaling within 0-­‐48hrs post HII, thus increasing the HT treatment window. PP1.2 -­‐1727 Susceptibility of Hippocampal Neurons to Hypothermia during Development Chae SA, Seo KA, Kim SH, Lee NM. Departments of Pediatrics, College of Medicine, Chung-­‐Ang University, Korea -­‐ [email protected] 59 Objectives: This study evaluated the extent of damage due to hypothermia in the mature and immature brain. Methods and Materials: Organotypic hippocampal cultures were prepared from 7 day old rat pups. Hippocampal tissue cultures at 7 and 14 days in vitro (DIV) were used to represent the immature and mature brain, respectively. The cultures were exposed at 25¢ªC for 0, 10, 30, and 60 min (n=30 in each subgroup). Propidium iodide fluorescent images were captured 24 and 48 hrs after hypothermic injury. Damaged areas of the Cornu Ammonis 1 (CA1), CA3, and dentate gyrus (DG) were measured using image analysis. Results: At 7 DIV, the tissues exposed to cold injury for 60 min showed increased damage in CA1 (P<0.001) and CA3 (P=0.005) compared to the control group at 48 hr. Increased damage to DG was observed at 24 (P=0.008) and 48 hrs (P=0.011). The 14 DIV tissues did not demonstrate any significant differences compared with the control group, except for the tissues exposed for 30 min in which DG showed less damage at 48 hr than the control group (P=0.048). In tissues at 7 DIV, CA1 (P=0.040) and DG (P=0.013) showed differences in the duration of cold exposure. Conclusions: The immature brain is more vulnerable to hypothermic injury than the mature brain. Cerebral palsy PP1.3 -­‐1950 Learning walking coordination through dynamic recurrent neural network in children with bilateral cerebral palsy Thomas Hoellinger, Guy Cheron, Bernard Dan. Laboratory of Neurophysiology and Movement Biomechanics, Université Libre de Bruxelles, Brussels, Belgium -­‐ [email protected] The existence of dedicated neuronal modules such as those organized in the cerebral cortex, thalamus, basal ganglia, cerebellum or spinal cord raises the question of how these functional modules are coordinated for appropriate motor behavior. Study of human locomotion offers an interesting field for addressing this central question. We describe the use of a dynamic recurrent neural network (DRNN) mimicking the natural oscillatory behavior of human locomotion for reproducing the planar covariation rule in both legs at different walking speeds. Neural network learning was based on sinusoidal signals integrating frequency and amplitude features of the first three harmonics of the sagittal elevation angles of the thigh, shank and foot of each lower limb. We verified the biological plausibility of the neural networks in healthy subjects and children with spastic bilateral cerebral palsy (GMFCSI-­‐II). Best results were obtained with oscillations extracted from the first three harmonics in comparison to oscillations outside the harmonic frequency peaks. We show application of this approach and discuss implications for neurophysiological understanding of the central pattern generator processing relevant oscillation signals and integrated management programs in cerebral palsy. PP1.4 -­‐1932 Botulinum toxin A in the treatment of cerebral palsy: stability of doses and inter-­‐session intervals across time for different patient groups Irene Nikaina, Katerina Foska, George Mitsou and Antigone Papavasiliou. Department of Neurology, Pendeli Children’s Hospital, Athens, Greece -­‐ [email protected] Aim: To review the experience with botulinum toxin A (BoNT-­‐A) of a paediatric multidisciplinary cerebral palsy clinic and test stability of doses and inter-­‐session intervals in different patient groups. Methods: Children and adolescents, younger than 18 years old with Spastc Cerebral Palsy (SCP) who received BoNT-­‐A injections were included in this study. Onabotulinumtoxin A and Abobotulinumtoxin A were used for multi-­‐level upper and/or lower limb injections, repeated as needed at >4 months intervals. Data on the dosage scheme, the frequency of the injections and the duration of the treatment along with patients' demographic data were collected. Results: 454 patients with a mean age of 5.3 years (± 3.6) received 1515 BoNT-­‐A sessions. Total doses/Kg of BoNT-­‐A were stable across sessions (p=0.244) but they were higher in children bilaterally (p<0.001) and more severely involved (p<0.001). In children with bilateral SCP doses/Kg demonstrated an increasing trend with time (p=0.030). Children older than 4 years were injected with similar doses/Kg as compared to the younger ones (p=0.109), but unlike younger patients their doses/Kg decreased with time (p=0.024). Doses/Kg in lower limbs were stable across time in both unilateral and bilateral SCP (p=0.177 and p=0.609, respectively). In bilateral SCP doses/Kg were higher in severely affected (p=0.020) and older patients (p=0.003); in unilateral SCP, children older than 4 years had lower doses/Kg in their lower limbs (p=0.061) versus the younger ones, with a decreasing trend as time evolved (p=0.016). Doses/Kg in upper limbs were stable across time in both unilateral and bilateral SCP (p=0.807 and p=0.106, respectively). Inter-­‐session intervals were longer as time evolved (p=0.003), when Onabotulinumtoxin A was used (p=0.019) and in older children (p=0.001). Conclusion: Age at treatment onset interfered with doses and intervals. Stability of doses/Kg injected and elongation of inter-­‐session intervals excluded secondary unresponsiveness to BoNT-­‐A due to antibodies. 60 PP1.5 -­‐1899 Management and interpretation of medical data related to Cerebral Palsy: the ICT4Rehab project Bonnechère B, Wermenbol V, Dan B, Salvia P, Le Borgne Y, Bontempi G, Vansummeren S, Sholukha V, Moiseev F, Jansen B, Rooze M, Van Sint Jan S. Laboratory of Anatomy, Biomechanics and Organogenesis (LABO), Université Libre de Bruxelles, Belgium -­‐ [email protected] Cerebral palsy (CP) is a complex disorder and the aetiology is probably one of the primary causes why different approaches are sometimes adopted in different hospitals for patient data management (anamnesis, clinical trials and functional analysis), and the decision-­‐making over the best treatment approach to offer to the patients. This variety of approaches is a problem for information and data exchange. The project ICT4Rehab (www.ICT4Rehab.org) is a multidisciplinary project funded by the Brussels region. ICT4Rehab develops a shared technology platform that addresses some of the above-­‐ mentioned problems. The platform offers hospitals the ability to store the data of their patients on a shared server data. A secured access then allows comparing the data of a particular patient with groups of patients (e.g. two groups of patients suffering for different pathologies within the same hospital, group a patient presenting the same pathologies from two different centres to compare methodology) or normal populations. This comparison is performed by data mining methods. The representation of data within the platform is based using today biomechanical and clinical standards. Serious gaming data are also integrated into the system. Clinical needs from several Belgian clinical centres have been gathered within a common shared technological structures developed by the project. Currently, patient files from three Brussels hospitals can be accessed by common statistical and reporting tools. Data integration of more hospitals is planned for the near future. The paradigm behind the ICT4Rehab project can be relatively extended to other efforts (for example, to connect to the creation of a central CP register in Europe (http://www.scpenetwork.eu/). Such shared information will allow producing more meaningful statistical results and facilitate consensus mechanism. The ICT4Rehab project seeks to expand its user group by inviting all motivated clinicians to test the structure of data sharing and mining tools developed by the project. PP1.6-­‐1680 Clinical patterns of secondary dystonia and choreoathetosis in dyskinetic CP Monbaliu E, Ortibus E, Prinzie P, De Cock P, Klingels K, Heyrman L, Feys H. KU Leuven, Department of Rehabilitation Sciences, Belgium; DC GID(t)S, Dominiek Savio Institute, Belgium -­‐ [email protected] Objectives: A better understanding of the clinical dystonia and choreoathetosis patterns in relation to motor classifications and brain lesions is essential to targeted therapy interventions. Therefore this study aimed: (1) to map dystonia and choreoathetosis across twelve body regions during voluntary asked activities and during rest; (2) to relate them with motor classifications; (3) to examine their relationship to lesions in the thalamus and basal ganglia. Material and Methods: Fifty-­‐five participants with dyskinetic CP (mean age 14 years 6 months, SD 4 years 1 month; age range 6-­‐22 years) were evaluated using the Dyskinesia Impairment Scale (DIS), measuring both dystonia and choreoathetosis, the Gross Motor Function Classification System (GMFCS) and the Manual Ability Classification System (MACS). Non-­‐parametric statistics (Wilcoxon signed-­‐rank test and Spearman’s rank correlation) were used to analyze clinical patterns and to relate them with the motor classifications. The Mann-­‐
Whitney U test was used to compare dystonia and choreoathetosis to the brain lesions. Results: Dystonia and choreoathetosis were simultaneously present across all body regions but participants showed significantly more dystonia than choreoathetosis (mean percentage 70.2% versus 26.7%, p<0.01). Also, dystonia and choreoathetosis were significantly higher during activity than at rest. Spearman correlations between the GMFCS and MACS with the DIS scores were high for dystonia, respectively 0.70 and 0.65. We found no significant correlations for choreoathetosis (rs=0.17 and 0.21). Finally, participants with pure thalamus and basal ganglia lesions clearly showed higher scores for choreoathetosis (p=0.03), but not for dystonia (p=0.44). Conclusions: In dyskinetic CP, dystonia and choreoathetosis are simultaneously present but with a higher dominance of dystonia. Higher scores for dystonia were clearly associated with more severe motor disability suggesting that dystonia, rather than choreoathetosis, has a larger impact on motor functions. Finally, pure thalamus and basal ganglia lesions seem to be particularly associated with choreoathetosis. Stroke and vascular disorders PP1.7 -­‐1983 Quality of Life One Year after Arterial Ischaemic Stroke in a Population-­‐Based Cohort Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, Parker AP, Wassmer E, Wraige E, Amin S, Edwards HB, O'Callaghan FJ. University of Bristol, United Kingdom -­‐ [email protected] 61 Objectives: To assess the quality of life (QoL) of children after arterial ischaemic stroke (AIS) and analyse factors associated with impaired QoL. Materials and Methods: A population-­‐based cohort of 96 children (aged >28 days to <16 years) residing in southern England with AIS onset between July 2008 and June 2009 were followed-­‐up at one year post AIS. QoL was assessed using the Pediatric Quality of Life Inventory (PedsQL). Children were also assessed using the Pediatric Stroke Outcome Measure (PSOM) and the Pediatric Stroke Recurrence and Recovery Questionnaire (RRQ) which have both been validated for use in paediatric stroke. Cognitive outcome was also assessed using a short form of the Wechsler Intelligence Scale for Children (WISC). Results: Parental-­‐proxy PedsQL scores were available for 62 children and child self-­‐ reported PedsQL scores were available for 34 children. The mean total-­‐scale PedsQL score by parental-­‐proxy was 75.5 (SD 20.2) which was significantly below the UK norm for healthy children (84.6, p=0.0008). The mean total-­‐scale PedsQL score by self-­‐report was 83.0 (SD 15.7) which was not significantly different from the UK norm (83.9, p=0.72). Increasing total PSOM scores (greater neurological impairment) was associated with lower parental (p<0.0001) and self-­‐reported (p<0.0001) PedsQL scores. Higher WISC scores were associated with higher parental (p=0.005) and self-­‐ reported (p=0.001) PedsQL scores. In a multivariate analysis PSOM sensorimotor deficits (but not other PSOM domains), female gender, and the presence of recurrent headache were all independently associated with lower parental-­‐proxy PedsQL scores. Conclusions: Parental-­‐proxy QoL scores are reduced one year after AIS but child self-­‐ reported scores are not. The presence of sensorimotor deficits is the most important predictor of reduced QoL. PP1.8 -­‐1980 Psychomotor development in children with posthaemorrhagic ventricular dilatation Laroche S, Hollander R, Ceulemans B. University Hospital Antwerp, Belgium -­‐ [email protected] Psychomotor development in children with posthaemorrhagic ventricular dilatation. Laroche S., Hollander R., Ceulemans B., departments of Neonatal Intensive Care and Paediatric Neurology of University Hospital Antwerp. Objective: Follow-­‐up study of posthaemorrhagic ventricular dilatation in a neonatal intensive care unit. Methods: We studied 47 children (period 2000 – 2010) with posthaemorrhagic ventricular dilatation retrospectively. Thirty-­‐one of them had a gestational age (GA) below 32 weeks, 10 between 32 and 37 weeks, and 6 were born term. Patiënts with congenital anomalies (2), postneonatal CNS damage (1) and those lost to follow-­‐up (1) were excluded. In the neonatal unit patiënts were followed with brain ultrasound. After hospital discharge their psychomotor development was assessed regularly. Results: We used Levene indices to make therapeutical decisions. In 17 patients the ventricular dilatation stabilised without intervention. We could stabilise 6 of the preterm neonates with a GA below 32 weeks with evacuating lumbar punctions only. In 6 patients the ventricular dilatation resolved using a subcutaneous reservoir. Twelve neonates needed a ventriculoperitoneal shunt. Two of the term neonates were treated with an external drain. There was an incidence of shuntinfections of 15%; Staphylococcus epidermidis was the main cause (62%). A central motor problem was seen in 12 (28%) of the children: 5 hemiplegias, 3 quadriplegias, 2 diplegias, and in another 2 hypotonia dominated the clinical picture. All but three of our patiënts with cerebral palsy walked independently around the age of 2,5 years. The incidence and severity of central motor problems was the highest in the group with a GA between 32 and 37 weeks. A mental developmental index below 70 was seen in 5 children (11%). Characteristics of autism spectrum disorder were diagnosed in 7 (15%). Conclusion: Only 12 out of 43 patients with posthaemorrhagic ventricular dilatation needed a ventriculoperitoneal shunt. Global outcome seems acceptable. PP2 Epilepsy 1 Peter Baxter PP2.0-­‐2107 A new approach to genetic diagnosis in early infantile epileptic encephalopathy and severe neurodevelopmental delay using a gene panel Mctague A, Scott RH, Moody H, Meyer E, Drury S, Fielding S, Trump N, Morrogh D, Lench NJ, Kurian MA. Neurosciences Unit, UCL-­‐Institute of Child Health, London, United Kingdom -­‐ [email protected] Objective: The early infantile epileptic encephalopathy (EIEE) syndromes are a heterogeneous group of conditions characterised by intractable seizures and developmental delay or regression. An increasing number of genetic causes are recognized; however genetic heterogeneity and phenotypic pleiotropy are common, rendering single gene testing impractical, time consuming and costly. We describe a pilot study of a new approach to genetic diagnosis using a multiple gene panel. Methods: Our gene panel included 29 genes associated with EIEE and developmental delay (including those cited on OMIM as EIEE 1-­‐13). For detection of small copy number variants, we utilised Roche Nimblegen custom design software to create an exon-­‐level 135K comparative genomic hybridization (CGH) array. In addition, Custom Haloplex sequence capture (Agilent) and 62 Illumina sequencing was undertaken using a MiSeq platform. We tested 48 children with severe developmental delay and early onset seizures. All had been pre-­‐screened with diagnostic microarray and methylation studies for Angelman’s syndrome, where appropriate. Results: Data quality was high (greater than 30x-­‐fold sequence data coverage, 90% of targeted coding bases) and no false positive calls were made. Mutations were identified in 5 patients (10%) and included nonsense mutations and deletions in a number of genes including MECP2 (2 patients), CDKL5, SLC9A6 and EHMT1. Conclusions: We report a multiple gene panel which has combined targeted, exon-­‐level array CGH with next-­‐generation sequencing technology to screen 29 disease causing genes in a cohort of patients with early onset seizures and neurodevelopmental delay. This diagnostic approach is likely to abolish to need for sequential gene testing in this group of disorders, and will no doubt improve genetic diagnosis (and likely provide earlier diagnosis) in this disparate range of conditions, thereby allowing better prognostication and genetic counselling for patients and their families. PP2.1-­‐1874 Ohtahara syndrome in two half siblings due to a novel SCN2A mutation Zerem Sheinman A, Halevy A, Michaeli-­‐Yossef Y, Goldberg-­‐Stern H, Blumkin L, Kivity S, Saitsu Hirotomo, Lev D, Leshansky-­‐Silver E, Lerman-­‐Sagie T. Pediatric Neurology Unit, Metabolic Neurogenetic Service, Wolfson Medical Center, Holon, Israel -­‐ [email protected] Objective: Ohtahara syndrome (OS) is a devastating early infantile epileptic encephalopathy characterized by early onset of tonic spasms, intractable seizures, suppression-­‐burst pattern on EEG and severe psychomotor retardation. De novo mutations in STXBP1 and ARX are major causes. SCN2A gene encodes the α1-­‐ subunit of the neuronal voltage-­‐gated sodium channel. Mutations in SCN2A have been reported to cause benign epileptic syndromes, such as benign familial neonatal-­‐ infantile seizures, which are inherited from an affected parent. In contrast, several de novo SCN2A mutations have been reported to cause more severe epileptic phenotypes such as Dravet syndrome. The objective of this report is to describe a gonadal mosaicism of SCN2A mutations in two half siblings with Ohtahara syndrome. Materials and Methods: We describe a patient with classic OS who presented on the first day of life with refractory tonic seizures. A suppression-­‐ burst pattern evolved later in life to modified hypsarrhythmia. The patient developed severe progressive microcephaly (-­‐6SD), profound mental retardation and spasticity and never achieved any developmental milestones. He died at the age of 5 years. The patient's DNA was screened for SCN2A mutations by high resolution melt analysis. The mutation was confirmed by Sanger sequencing. Results: The patient was found to have a novel missense mutation (c.4007C>A p.S1336Y). The parents were negative for the mutation. The father has another son from a different mother presenting as OS. The sibling with OS carries the same mutation; thus suggesting a diagnosis of paternal gonadal mosaicism. Conclusions: The broad clinical spectrum of SCN2A mutations should include Ohtahara syndrome. This is the first report of familial OS due to germline mosaicism. It has important consequences for genetic counseling when SCN2A mutations appear to occur de novo. PP2.2 -­‐2026 Novel compound heterozygous mutations in TBC1D24 cause familial Malignant Migrating Partial Seizures of Infancy Milh M, Falace A, Villeneuve N, Vanni N, Cacciagli P, Assereto S, Nabbout R, Benfenati F, Zara F, Chabrol B, Villard L, Fassio A. INSERM U 910 and APHM Service de Neurologie pédiatrique, Marseille, France -­‐ [email protected]­‐hm.fr Early-­‐onset epileptic encephalopathies (EOEEs) are a group of rare devastating epileptic syndromes of infancy characterized by severe drug resistant seizures and electroencephalographic abnormalities. The current study aims to determine the genetic etiology of a familial form of EOEE fulfilling the diagnosis criteria for malignant migrating partial seizures in infancy (MMPSI). We identified two inherited novel mutations in TBC1D24 in two affected siblings. Mutations severely impaired TBC1D24 expression and function, which is critical for maturation of neuronal circuits. The screening of TBC1D24 in an additional set of 8 MMPSI patients was negative. TBC1D24 loss of function has been associated to idiopathic infantile myoclonic epilepsy, as well as to drug resistant early onset epilepsy with intellectual disability. Here we describe a familial form of MMPSI due to mutation in TBC1D24, revealing a devastating epileptic phenotype associated with TBC1D24 dysfunction. PP2.3 -­‐2143 Clinical and neuroimaging features of patients with ESES Deniz Yüksel, Mehpare Ozkan, Ayşe Aksoy, Ülkühan Kaya. Dr. Sami Ulus Children's Health and Diseases Training and Research Hospital, Ankara, Turkey -­‐ [email protected] 63 Objective: ‘‘Electrical status epilepticus during slow wave sleep’’ (ESES) is characterised by the electroencephalographic pattern of continuous spike waves during slow wave sleep (CSWS) and variable neuropsychological impairments. The aim of this study was to evaluate the clinical and neuroimaging features of ESES and to investigate possible risk factors. Methods: In a retrospective study, we analysed the demographic and clinical data and waking after sleep EEG slow waves of 16 patients with ESES. The patients showed continuous spike waves (>85%) associated with regression of cognitive functions. Results: The mean age was 9.37 ± 3.15 (range 3-­‐15 years), 7 male and 9 female patients who had been diagnosed with ESES were enrolled in the study. The age at the onset of their first seizure was 2.93 ± 2.48 (range 0-­‐10 years), the mean age at the onset of the ESES clinic was 7.5 ± 2.78 (range 2-­‐13 years). Their respective medical histories showed 2 patients with a prematurity, 3 patients with perinatal asphyxia, 2 patients with congenital cytomegalovirus infections, 2 patients with neonatal convulsions, 1 patients with neonatal stroke, 1 patients with intrauterine growth retardation, and 2 patients with febrile convulsions. Our neurological examination revealed 8 patients (50%) with microcephaly, 13 patients (81%) with mental retardation, 6 patients (37%) with cerebral palsy, 5 patients with speech delay, and 2 patients with ataxia. Brain magnetic resonance imaging findings showed malformations of cortical development (schizencephaly, lissencephaly, cortical dysplasia), corpus callosum agenesis, periventricular leukomalacia, cortical atrophy, thalamic lesions, calcifications, hypoxic ischemic lesions, stroke, and only five patients had normal results. Except three patients the remaining patients underwent antiepileptic drug polytheraphy. Conclusions: Early and effective therapy aiming to decrease the duration of ESES may also help prevent permanent neuropsychological impairment, though no consensus exists as to the optimal treatment. PP2.4 -­‐2121 Recurrent status epilepticus and dystonia caused by a mutation in SCN8A Peake D, Anderson J, Anderson C, McKee S. Paediatric Neurology Department, Royal Belfast Hospital for Sick Children, United Kingdom -­‐ [email protected] Introduction: Several voltage-­‐gated sodium-­‐channel genes have been implicated in seizure disorders, including SCN1A, SCN2A, SCN3A, and SCN9. SCN8A encodes the neuronal sodium channel NaV1.6 that is highly abundant in the CNS, and recently linked with infantile epileptic encephalopathy. We present a 16 year-­‐old female with a severe epileptic encephalopathy associated with an SCN8A mutation detected by whole-­‐exome sequencing. Case report: The proband presented at age 8 months with clustering of frequent myoclonic seizures -­‐ up to 50/day, not associated with fever or illness. Subsequent recurrent generalised tonic clonic seizures and frequent episodes of status epilepticus (from age 1y) resulted in >25 admissions to hospital, often involving PICU. Later seizures (refractory to treatment) were more typical of clustering of focal motor, tonic and atonic seizures. The last EEG showed slow spike-­‐and-­‐wave discharge superimposed on abnormal, slow background, frequency 1.5-­‐
2.0Hz (Lennox-­‐Gastaut). Several neuroimaging studies (MRI & CT) between 8m and 16y were normal. There was no period of normal development; neurological examination revealed a normocephalic child with central hypotonia, generalised limb dystonia and contractures. There were no dysmorphic features other than small, cold hands and feet. Death occurred at 16 years following a period of hospital admission with intractable seizures and acute chest infection on a background of increasing respiratory compromise. Karyotype and microarray-­‐CGH were normal. Whole-­‐exome sequencing revealed a de novo heterozygous missense mutation p.G1625R in SCN8A. Conclusion: Further cases of SCN8A-­‐associated early infantile epileptic encephalopathy will almost certainly come to light via exome sequencing, and help clarify the phenotypic spectrum and management options. PP2.5 -­‐2056 The Role of Ictal Subtraction SPECT for the Diagnosis of Focal Cortical Dysplasia in An Infant Kara B, Maras H, Yalcin EU, Aktan F, Demirbas F, Anik Y, Ciftci EA, Gorur GD. Kocaeli University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Kocaeli, Turkey -­‐ [email protected] Infantile epileptic encephalopathies cause global developmental and intellectual retardation without effective treatment. Cortical dysplasias are an important cause of infantile epileptic encephalopathy, because surgical treatment of the epileptic foci may improve the prognosis. Cortical dysplasias cannot be shown with cranial magnetic resonance imaging in every patient, and PET and/or SPECT have been shown to be valuable tests in the detection of seizure foci. In the literature, ictal subtraction SPECT appears to be more sensitive than other tests. 4-­‐month-­‐old girl was reported for hypomotor and complex focal seizures, and nystagmus-­‐like eye movements. Seizures could not be controlled despite different antiepileptics. Interictal electroencephalograms (EEG) showed bilateral occipital epileptiform activity. Cranial magnetic resonance imaging was normal. During video EEG monitorization, a lot of seizures were recorded, and all of them were from the occipital lobes, especially left. PET 64 analysis was not informative. Ictal SPECT showed left occipital parasagittal hyperperfusion area, and perfusion of this area returned to normal with interictal SPECT. A new cranial magnetic resonance imaging was ordered, and we observed thin cortex (2.7 mm) and insufficient sulcation at the left parasagittal occipital lobe compatible with ictal SPECT. The diagnosis of the patient was intractable epilepsy due to focal cortical dysplasia, and now she is being evaluated for surgical treatment. Ictal subtraction SPECT can provide important information in the detection of seizure foci and preoperative evaluation of medically intractable epilepsy. PP2.6 -­‐2050 Crossed cerebellar diaschisis with non-­‐refractory epilepsy Monier A, Aouni S, Dan B. Clinique de Neurologie, Hôpital Universitaire des Enfants Reine Fabiola, ULB, Brussels, Belgium -­‐ [email protected] We report a 5 year-­‐old boy who presented with iterative generalized seizures lasting for 24 hours with febrile otitis media. He had previously suffered one status epilepticus episode at 18 month and one short-­‐lasting seizure at 4 years, with normal brain MRI. He also presented a mild coordination disorder. On presentation, MRI showed left fronto-­‐occipital gliotic lesions with normal diffusion-­‐weighted images and MRA. EEG showed moderate left fronto-­‐parietal epileptiform activity. After acute management, the child was rapidly seizure-­‐free. Two-­‐year follow-­‐up revealed no seizure under valproic acid, mild right upper limb paresis, coordination disorder and executive dysfunction, necessitating integration in a special school. Repeat brain MRI (after 1 and 2 years) showed an increase of the white matter lesions and significant atrophy of the right cerebellar hemisphere, with normal MRA. EEG shows sustained epileptiform activity in the left fronto-­‐parietal region and no continuous spikes and waves syndrome during sleep. This evolution is consistent with crossed cerebellar diaschisis (CDD), a rare condition where a cerebellar lesion develops remote from a controlateral supratentorial primary site of injury, presumably due to loss of afferentation in the corticopontocerebellar tract connecting the two areas. Metabolic depression, retrograde degeneration and excitotoxicity are the main suggested mechanisms. In children, most cases are related to encephalitis and tumor, rarely to stroke, migraine and refractory focal epilepsy. The present report suggests that CDD can occur without clinical seizure, potentially due to remaining focal epileptiform activity. In our patient, it is highly probable that the slowly progressive white matter injury of unknown origin potentiates the phenomenon. Whether epileptic subclinical activity should be treated more aggressively remains questionable. PP2.7 -­‐2032 Benign Familial Infantile Epilepsy Due To PRRT2 Gene Mutation Without Paroxysmal Kinesigenic Dyskinesia Maras H, Kara B, Yalcin EU, Iseri SU, Ozbek U. Kocaeli University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Kocaeli, Turkey -­‐ [email protected] Mutations of PRRT2, which encodes “proline-­‐rich transmembrane protein 2”, have been identified in patients with benign familial infantile sizures (BFIS), infantile convulsions with choreoathetosis (ICCA) syndrome and familial paroxysmal kinesigenic dyskinesia (PKD). All these phenotypes had autosomal dominant inheritance. PRRT2 is a presynaptic protein, and likely has a role for exocytosis and neurotransmitter release. Recent studies show that PRRT2 gene mutation is the most common cause of BFIS. 6-­‐month-­‐old boy had hypomotor seizures. His brother, maternal aunt, and maternal uncle also had seizure history in infancy. All patients had normal neurologic development. Seizures of the index patient and his brother were controlled with phenobarbital, maternal aunt and maternal uncle of the index patient were free of seizures, and had no history of antiepileptic medication. BFIS was diagnosed due to seizures beginning in infancy and normal neurologic development. PRRT2 gene mutation was observed in the affected patients. All affected patients were reevaluated for paroxysmal kinesigenic dyskinesia, but there were no history or clinical evidence of dyskinesia. PRRT2 should be the first gene to screen in patients with BFIS. Paroxysmal kinesigenic dyskinesia may not accompany in all patients with PRRT2 mutations. PP2.8 -­‐1767 Safety of adjunctive zonisamide in paediatric epilepsy patients: results from a pooled analysis of 17 studies Giorgi L, Patten A. Eisai Limited, Hatfield, Herts, UK -­‐ [email protected] Objective: To assess the safety of adjunctive zonisamide in paediatric epilepsy patients.A pooled analysis of 17 studies (including four randomised, double-­‐blind trials) was conducted. Safety population comprised patients aged ≤16 years receiving ≥1 study drug dose. Assessments included treatment-­‐emergent adverse events (TEAEs), clinical laboratory parameters, vital signs and electrocardiography. Analysis included 398 patients (<12 years, n=191; 12–16 years, n=207). All but seven received zonisamide as adjunctive therapy. Mean zonisamide dose was 253 mg/day and mean exposure duration was 319 days. Most TEAEs were of mild or moderate intensity; the 65 most frequently reported treatment-­‐related TEAEs (≥5%) being decreased appetite (13.7%), somnolence (12.3%), fatigue (9.6%), irritability (7.5%) and lethargy (5.5%) in patients aged 6–11 years, and decreased appetite (15.9%), fatigue (10.1%), somnolence (8.7%), weight decreased (7.7%), dizziness (7.7%), headache (6.8%) and insomnia (5.3%) in patients aged 12–16 years. Incidence of serious zonisamide-­‐related TEAEs was 3.5% overall. Seven patients experienced TEAEs resulting in death, two of which were judged as related to zonisamide treatment (status epilepticus, possibly related; multi-­‐system organ failure, definitely related). One case of death (SUDEP) in a placebo-­‐treated patient occurred in Study E2090-­‐E044-­‐317. However, this study was excluded from the pooled analysis, having not met the entry criterion of including ≥3 zonisamide-­‐exposed paediatric patients. TEAEs led to discontinuation of 10.3% patients; most commonly, lethargy (1.0%) and fatigue (1.0%). 28 patients (7.0%) had TEAEs of decreased weight and 78 (19.6%) had TEAEs of decreased appetite. There were no reports of Stevens Johnson Syndrome or toxic epidermal necrolysis. Twenty-­‐eight patients had decreased bicarbonate levels and two had TEAEs of decreased bicarbonate. No changes in vital signs of clinical concern were observed and there were no reports of clinically significant electrocardiogram abnormalities with zonisamide treatment. No new or unexpected safety findings emerged when zonisamide was used as adjunctive treatment in paediatric patients. PP2.9 -­‐2030 Intelligence two years after epilepsy surgery in children Viggedal G, Olsson I, Carlsson G, Rydenhag B, Uvebrant P. Sahlgrenska University Hospital, Gothenburg, Sweden, Department of Paediatrics, Institute of Clinical Sciences at the Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden, Department of Neuropediatrics, Medical Center of Schleswig-­‐Holstein, Sweden -­‐ [email protected] Objectives: To evaluate cognitive functions before and two years after surgery in a consecutive series of paediatric patients. Specific objectives were to relate cognitive effects to seizure outcome and to explore the effect on IQ in children with a low preoperative IQ. Matrial and Method: Ninety-­‐four children underwent epilepsy surgery in the years 1987 to 2006 at Sahlgrenska University Hospital in Gothenburg and had complete pre-­‐ and postoperative assessments of intelligence. The Swedish versions of the Griffiths’ Developmental Scales and the Wechsler scales were used to assess intelligence. Results: Higher or unchanged full-­‐scale IQ and verbal IQ scores two years after surgery were recorded in 43 (46%) of the 94 children, and 51 (54%) had higher or unchanged performance IQ. Before surgery 49 (52%) had an average full-­‐scale IQ (>69), 17 (18%) had mild learning disabilities (IQ 50 to 69) and 28 (30%) severe learning disabilities (IQ<50). Sixty-­‐five of the children (69%) had at least a 75% reduction in seizure frequency and 47 (50%) became seizure-­‐free. A significant difference in median levels of change in full-­‐scale IQ, verbal IQ and performance IQ was found between the seizure-­‐free and not seizure-­‐free children two years after surgery A higher or unchanged full-­‐scale IQ was found in four of the ten seizure-­‐free and in six (33%) of 18 not seizure-­‐free children with severe learning disabilities. Six (86%) of 7 seizure-­‐free children with a mild learning disabilities had a higher or unchanged full-­‐scale IQ, compared with three of the ten not seizure-­‐free. Eighteen (60%) of 30 seizure-­‐free children with an average IQ had a higher or unchanged full-­‐scale IQ compared with six (32%) of the 19 not seizure-­‐free children. Conclusion: Seizure freedom is the most important factor for the prognosis of cognitive development, regardless of the intellectual level of the child before surgery. PP3 Neuromuscular and movement disorders Neuromuscular Michèl Willemsen PP3.0 -­‐2024 Congenital myopathy associated with mutations in skeletal muscle alpha-­‐actin gene (ACTA1) Coppens S, Dan B. Belgium -­‐ [email protected] Objectives: To describe the clinical and histopathological presentation of ACTA1 congenital myopathy. Material and methods: We reviewed the history, clinical examination, muscular histopathology and genetics results in three patients with a genetically proven or suspected ACTA1 congenital myopathy. Results: The first two patients have a very similar clinical presentation with severe hypotonia at birth, high-­‐arched palate, facial weakness, prominent neck flexion weakness, scoliosis and nocturnal hypoventilation requiring nocturnal non-­‐invasive ventilation, and delayed motor milestones but eventual acquisition of independent walking. Muscle pathology was non-­‐specific in one patient and showed congenital fiber-­‐type disproportion in the other one. A dominant, de novo, missense mutation was identified in ACTA1 gene in both patients: c.16G>A in the first and c.925C>T in the 66 second one. The third patient showed a severe fetal presentation with polyhydramnios and akinesia, and severe neonatal respiratory insufficiency causing death soon after birth. Muscle pathology showed a severe myofibrilllary disorganisation with large accumulations of thin myofilaments, that are highly suggestive of actin myopathy. Genetic search for ACTA1 mutation is still in progress in this third patient. Conclusion: ACTA1 mutations are a common cause of congenital myopathy associated with various muscle pathology types, with two specific patterns: actin myopathy and intranuclear rods. Mutations sites occur all along the gene and explain the important variety in the clinical presentation that ranges from a severe neonatal form with akinesia and respiratory insufficiency requiring mechanical ventilation to a milder form compatible with life into adulthood. The striking feature in the latter patients is the importance of the axial, facial, bulbar and respiratory weakness contrasting with the relative preservation of limb strength, compatible with independent walking. PP3.1 -­‐1795 Muscular dystrophies and congenital myopathies in childhood. Incidence and frequency of individual subtypes diagnosed in a thirty year period Thorarinsdottir BK, Tulinius M, Darin N. Gothenburg, Sweden -­‐ [email protected] Muscular dystrophies and congenital myopathies often produce a similar clinical picture of muscle weakness and atrophy. Population studies that include muscular dystrophies and congenital myopathies are rare, it is not well studied how common these disorders are. The aim of the study was to identify all the patients diagnosed with muscular dystrophies and congenital myopathies in childhood over a thirty year period, between 1979 and 2009, and to describe the cumulative childhood incidence of these disorders. The geographic area studied was the region of western Sweden. We analyzed registers from local and regional pediatric hospitals and local and regional child rehabilitation centers, registers of muscle biopsies, neurophysiologic examinations and genetic analyses. The total number of identified cases were 207 patients. 139 patients with muscular dystrophies that were divided into 63 patients with Duchenne muscular dystrophy, 14 with Becker muscular dystrophy, 21 with limb-­‐ girdle muscular dystrophy, 15 with facioscapulohumeral muscular dystrophy, 3 with Emery–Dreifuss muscular dystrophy and 23 with congenital muscular dystrophy. 68 patients were diagnosed with congenital myopathy. The cumulative childhood incidence of Duchenne muscular dystrophy and congenital muscular dystrophy are similar to what have been found in previous studies from Sweden. The incidence of congenital myopathy is higher. In this group the majority of patients had unspecific muscle morphological findings. PP3.2 -­‐1699 The effect of steroids on puberty in Duchenne muscular dystrophy Dooley JM, Bobbitt SA. Nova Scotia, Canada -­‐ [email protected] Steroids have greatly enhanced the quality of life and longevity of patients with Duchenne muscular dystrophy (DMD) but often with associated side effects. All patients with DMD from the Canadian Province of Nova Scotia are followed in our Neuromuscular clinic at Dalhousie University in Halifax. We assessed the pubertal development of our patients who were 14 years or older and had been treated with deflazacort as their only glucocorticoid. Puberty was classified as delayed if the patient was 14 years or older and had testicular volume of less than 4 cc. Gonadotropin Releasing Hormone (GnRH) stimulation testing was performed, with LH and FSH measured before and 40 minutes following administration of a GnRH agonist . Half (6 of 12) of the boys who were treated with deflazacort as their only glucocorticoid had pubertal delay. There was no difference in the age of onset, dose or duration of deflazacort therapy between those who did and did not have delayed puberty. Deflazacort was used for 5-­‐16 years among those with pubertal delay and for 8-­‐15 years for those with normal puberty. Delayed puberty should be included and studied in future trials that address different doses and schedules of deflazacort therapy in DMD. PP3.3 -­‐1808 Disease-­‐related symptoms and activities of daily living: a novel survey of patients with nonsense mutation Duchenne muscular dystrophy Reha A, Barth J, Elfring GL, Spiegel R. South Plainfield, New Jersey, USA -­‐ [email protected] Objectives Health-­‐related quality of life in Duchenne muscular dystrophy (DMD) is not well understood, and there is a need for a sensitive disease-­‐specific questionnaire. We developed a survey of symptoms and activities of daily living (ADL) which we piloted in an ongoing open-­‐label study of ataluren in nonsense mutation DMD. We describe the survey design and provide a preliminary summary of baseline data in 18 patients. Substantial additional data will be available at the time of the EPNS meeting. Materials and Methods The survey is administered by site personnel to the same respondent (patient/parent/caregiver) throughout the study. At baseline (prior to initiation of ataluren treatment), information is collected on disease-­‐related symptoms/ADL 67 (classified into six pre-­‐specified categories). Respondents then rate any changes in these symptoms/ADL on a 5-­‐
point Likert scale at each 12-­‐week visit during the study. Results Patients representing various degrees of ambulatory disability were included. Physical functioning was the most commonly identified category at baseline (32 times by 14 patients), followed by general energy level (9 times; 9 patients) and cognition/school functioning (6 times; 6 patients). Sleep and emotional/social functioning were each identified by two patients, and ‘other’ by one. Walking, climbing stairs and standing up were the most common aspects of physical functioning reported at baseline. Concentration and school performance featured in the cognition/school functioning category. Conclusions Patient/caregiver reports are an essential component in the clinical assessment of DMD. We have developed a survey to allow patients/caregivers to self-­‐identify specific ADL affected by DMD and assess response to treatment. This is intended to aid in the construction of a new instrument sensitive to detect changes in ADL/disease symptoms. The survey is being piloted in an ongoing open-­‐label ataluren trial in nmDMD and will be used in a pivotal Phase 3 randomized study to complement functional outcome measures. PP3.4 -­‐1800 Ryanodine myopathies without central cores Rocha J, Taipa R, Melo Pires M, Oliveira J, Santos MR, Santos M. Neurology Department -­‐ Hospital de Braga, Portugal -­‐ [email protected] Objectives: Myopathies related to Ryanodine Receptor 1 (RYR1) mutations are one of the most frequent and their classical histological presentation is central core myopathy. Clinical variability and hystopathological overlap with other myopathies is increasingly recognized, promoting diagnostic difficulties. Here we report 3 cases of RYR1 myopathies without central cores and highlight their clinical particularities. Materials and Methods: Patients were selected from clinical database with the following criteria: congenital myopathies without cores and RYR1 mutation. We identified three unrelated patients. Results: Female, 15 years-­‐old, with maternal family history of limb weakness. She had lower limb weakness complaints from age of 5, presenting a progressive scoliosis since the age of 10. She presented a mild proximal tetraparesis with axial and facial involvement. Muscle biopsy revealed marked type 1 fiber predominance. Female, 18 years-­‐old, with history of easy fatigue. She developed a progressively worsening of muscle weakness and rapidly progressive scoliosis from age 11, with need of surgical treatment at 14 and need of BIPAP. She presented mild proximal tetraparesis and severe axial involvement. Muscle biopsy revealed abnormal fiber size variation, mild endomysial fibrosis, areas of increased adipose tissue and type 1 fiber predominance. Male, 11 years-­‐old, with muscle weakness since age 2 with slowly progressive course. At the age of 10 he had facial paresis with slight disphonia, moderate tetraparesis mainly proximal and in lower limbs. Muscle biopsy showed fiber typing uniformity with oxidative enzymes. Different RYR1 mutations were identified in all patients. Conclusions: These cases illustrate early-­‐onset myopathies, progressing later in childhood, two with a predominant axial involvement. Hystopathological examination revealed either a uniformity of fiber type or a clear predominance of type 1 fibers without central cores. These cases reinforce the need to recognize the hystopathological variability of RYR1 myopathies, stressing the lack of clinical correlation with histological non-­‐specific finding. PP3.5 -­‐1554 Multidisciplinary approach to rare diseases – Friedreich's ataxia Malenica M, Kukuruzovic M, Krakar G, Cvitanovic Sojat Lj. University hospital centre Sestre milosrdnice, pediatrics clinic, department of neuropediatrics, Croatia -­‐ [email protected] Aim: To emphasize the need for multidisciplinary approach in determining the diagnosis and in treatment of children with Freidreich's ataxia (FA)-­‐ autosomal recessive neurodegenerative disease. Case report: A female 15,5 years old girl with uneventful family history and normal psychomotor development was admitted due to clumsiness. She previously received an ortosis due to thoracic scoliosis. During her stay we noticed mild ataxia, tremor, and nystagmus with neurographical finding of complete loss of sensory potentials with demyelination signs and borderline speed of conduction on lower extremities. DNA analysis determined a full mutation of frataxin on chromosome 9. Heart ultrasonography confirmed concentric hypertrophic cardiomyopathy. Continuous measuring of systemic pressure diagnosed hypertension with high risk for damage of target organs. There was no other cause of hypertension so it was most likely a consequence of hypertrophic cardiomyopathy. With ACE inhibitor therapy she achieved pressure normalization. She is receiving support therapy with idebenon, coenzyme Q10, and vitamin E. She receives physical therapy following spine surgery due to scoliosis. Besides regular visits to pediatric neurology specialist she is also seeing a cardiologist, ENT specialist, ophthalmologist, and psychologist. Her neurological status is according to International Cooperative Ataxia Rating scale deteriorating despite support therapy. Conclusion: Out case emphasizes the need for continuous multidisciplinary approach to patients with FA which in our patient so far includes a pediatric neurology 68 specialist, pediatric cardiology specialist, pediatric nephrology specialist, physical therapy specialist, ENT specialist, ophthalmologist, and psychologist. Movement disorders PP3.6 -­‐2106 Early Onset Ataxia – an International Database Steinlin M, Baxter P, Boltshauser E, Brankovic V, Catsman-­‐Berrevoets C, Bertini E, Kennedy C, Mancini F, Nemeth A, Schöls L, Sival D, Synofzik M. Department of Neuropaediatrics, Development and Rehabilitation, University Children's Hospital, Berne, Switzerland -­‐ [email protected] Background: Problems of ataxia are of increasing interest over the last decade. There are indefinite variable etiologies of congenital and early onset ataxias (EOA)-­‐ only very few clearly defined by genetics and/or pathophysiology. We aim to improve knowledge in this field by creating a large-­‐scale database that will allow (i) to identify the frequency of different EOAs, (ii) to assess their natural history, and (iii) to establish a large cohort of unexplained EOA cases that will be accessible for next generation sequencing technologies to identify both known and novel genes presenting with EOA. Methods: By a pseudoanomynised, webbased registry we will collect data on children/young adults with congenital or early onset (start <40years of age) ataxias. The following data will be registered: demographics; clinical course including SARA scale, INAS (information on non ataxia symptoms) and quality of life; laboratory and electrophysiological work up; neuroimaging and genetic results. DNA should be collected for each patient locally. Application for collaboration: Accepted for collaboration are people interested in the field of ataxia who are either experienced in management/counseling of ataxic patients or have made other important contribution to the field of ataxia. Each collaborator has access to his own register data. By submission and acceptance of a more comprehensive research project to the steering committee of the EOA group, the necessary data from the registry for this project will given free to the individual researcher. Application to become a collaborator will have to be submitted to the steering group EOA. Summary: By an international approach we aim to collect data on children and young adults with congenital or early onset ataxia – to improve understanding, form phenomelogical groups, to solve underlying pathophysiology, to assess the frequency of established genes and identify novel EOA genes. PP3.7 -­‐2011 Acute and subacute chorea in a French series of 37 children Doummar D, Grisel C, Roubertie A, Héron B, Gras D, Laroche C, Sabouraud P, jMotte J, Maincent K, Isapof A, Rodriguez D, Billette De Villemeur T. Neuropédiatrie, Centre de référence mouvements anormaux de l’enfant, Hôpital Trousseau, Paris, France -­‐ [email protected] Chorea is characterized by brief, abrupt, irregular, non stereotyped movements. The recognition of this movement disorder is mandatory as it would facilitate proper management. We report 37 children with acute/ subacute chorea followed by multiple french neuropediatrics departments. The aim of this retrospective study work is to determine the clinical, etiological characteristics, treatment, and outcome. In our study, we found that chorea was unilateral (15/37), which had no localizing value. It was isolated (12), or associated with behaviour changes or altered consciousness, and proceeded by infectious episodes (16). The inflammatory causes were the most common (20/37, 54 %), including 7 Sydenham’s chorea, 5 post infectious basal ganglia encephalitis, 2 anti NMDAR encephalitis, 3 systemic lupus erythematosus , and 1 paraneoplastic syndrome. The other etiologies were vascular (8/37, 22%), metabolic or degenerative (n=3), and due to vitamine B12 deficiency (n=1). Repeated explorations before diagnosis were needed in some cases. Despite this, 5 cases remained with unspecific etiology. The evolution of chorea was favourable (n=15) with or without symptomatic treatment, especially in vascular origin. Nevertheless, 3 status choreic dystonicus required emergency pallidal deep brain stimulation. Furthermore, treatment was specific of the underlying etiology. One prospective case series of acute chorea (n=20) is reported in the literature. As in our study, autoimmune and inflammatory causes are the most frequent. On the other hand, drugs or toxic induced-­‐ chorea are reported, as hyperthyroidism. No psychogenic movement disorder is found. Children with Huntington disease rarely present with chorea. Brain MRI with angiography is mandatory to search for basal ganglia abnormalities, (especially in vascular, or metabolic disorders). However it can be normal (autoimmune or post pump chorea). This study highlights the various causes of acute chorea in children, which guides the treatment. Noteworthy, the diagnosis may be difficult and need a long term follow up. 69 PP3.8-­‐1704 Ataxia with vitamin E deficiency in Norway Elkamil AI, Johansen KK, Aasly JO. Department of Paediatrics, St. Olav’s University Hospital, Trondheim, Norway -­‐ [email protected] Ataxia with vitamin E deficiency (AVED) is a rare neurological disorder which usually starts in childhood. If not recognized and treated it usually leads to severe neurological impairment. The phenotype is variable but most patients have progressive gait ataxia, dysarthria and polyneuropathy. AVED is a very rare disorder in northern Europe with unknown prevalence. We performed a search in all health regions in Norway to get some estimate of the prevalence in a northern Scandinavian country. The prevalence of ataxias in the southern and eastern regions had been published in 2012. We had one case diagnosed in our department located in Central Norway and one additional was found in the northern part of the country. This was achieved by studying official reports. In all 3 cases the age of onset was in early childhood, around the age of 4 -­‐ 6 years. They all experienced gait ataxia and dysarthria. Sadly, none was diagnosed and treated before they had developed severe neurological deficits. The genetic testing showed that all three had pathogenic mutations in the TTPA gene. All were carriers of the non-­‐sense c.400C>T mutation, one was homozygous for that mutation the 2 others were compound heterozygous, either with c.358G>A or c.513_514insTT. The homozygous carrier was by far the most severely affected patient. In conclusion: We postulate that the prevalence of AVED in Norway is around 1 per million inhabitants and if not diagnosed and treated in early childhood it will progress to severe neurological deficits. PP3.9 -­‐1603 Alternating hemiplegia in childhood – a clinical and genetic study Nevsimalova S, Krepelova A, Kemlink D. Department of Neurology, Charles Universtity, 1st Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic -­‐ [email protected] Objective: Alternating hemiplegia in childhood (AHC) is a rare neurological disorder characterized by early-­‐onset episodes of hemiplegia, various paroxysmal symptoms including dystonic features and developmental impairment. Recently, de-­‐novo mutations in ATP1A3 gene were found in patients with AHC2 resembling allelic early rapid-­‐onset dystonia parkinsonism, classified as DYT12. Patients and Methods: Five AHC patients (3 boys, 2 girls) underwent a longitudinal (5-­‐ 20 years) neurological follow-­‐up including neurophysiological examinations (EEG, evoked potentials, video-­‐polysomnography), and neuroimaging, particularly a SPECT study. For Sanger sequencing of the ATP1A3 gene, DNA from peripheral blood samples was extracted and primers for DNA amplification and sequencing were used to cover all coding regions of the gene. Results: Paroxysmal dystonic features increased with age like other movement disorder symptoms including choreiform movements. Similarly to DYT12, dystonic features developed some signs of a rostrocaudal gradient (orofacial dystonia with dysphagia, dyspnoea). The mystery of AHC symptoms completely disappearing during sleep and reappearing again a few minutes after awakening, supports also movement disorder aetiology. ATP1A3 analysis revealed a pathogenic mutation c.2401G>A p. (Asp801Asn) in two patients, c.2839G>A p. (Gly947Arg) in one and 2839G>C p. (Gly947Arg) in another one. No mutation or deletion was detected in the last patient with atypical late onset of the disease. Conclusions: Our study suggests that AHC2 and DYT12 may represent a phenotypic continuum of one clinical entity, however, further genotype-­‐phenotype studies are desirable to prove this hypothesis. AHC patients may represent the most severe type of ATP1A3-­‐associated dystonic movement disorder, while DYT12 patients would present only a mild variety of the same disease. PP4 Neurometabolic disorders Rudy Van Coster PP4.0 -­‐1506 Longitudinal outcomes from the international disease registry for Niemann-­‐Pick disease type C (NP-­‐C) Pineda M, Mengel E, Wijburg FA, Vanier MT, Schwierin B, Muller A, Drevon H, Patterson MC. Fundació Hospital Sant Joan de Déu, CIBERER, Barcelona, Spain -­‐ [email protected] Objective: This disease registry was initiated to evaluate the long-­‐term disease course of NP-­‐C in clinical practice. The current analysis focuses on patients who received miglustat continuously between enrolment and last follow up visit, based on data collected from September 2009 to August 2012. Methods: All patients diagnosed with NP-­‐
C, irrespective of treatment, were eligible for inclusion in this multicentre, prospective, observational cohort study. Patient demographics, disease characteristics, disability status and treatment data were collected. Disability status was evaluated using a disease-­‐specific disability scale that rated four domains: ambulation, 70 manipulation, language and swallowing from 0 (normal) to 1 (worst). Patients were categorised as ‘improved/stable’ if ≥3 out of these 4 domain scores were lower or unchanged between enrolment and last follow-­‐up visit, or as ‘worsened’ if <3 domain scores were lower or unchanged. Results: Eighty out of the 190 enrolled patients (mean [SD] age at enrolment 17.8 [11.5] years; 52.5% female) received miglustat continuously throughout the observation period; mean (SD) exposure 1.19 (0.69) years. Among 74/80 patients with available data, the mean (SD) age at neurological onset was 9.9 (9.3) years. Ten (14%) patients had early-­‐infantile onset (aged <2 years), 24 (32%) had late-­‐infantile onset (2 to <6 years), 24 (32%) had juvenile onset (6 to <15 years), and 16 (22%) had adolescent/adult (≥15 years) onset of neurological manifestations. Mean (95%CI) composite disability scores at enrolment and last follow-­‐up visit were 0.39 (0.34, 0.45; N=75) and 0.45 (0.39, 0.51; N=76), respectively. Overall, 52/72 (72%) patients were categorised as ’improved/stable’; 20/72 (28%) were categorised as ‘worsened’. Safety and tolerability findings were in line with previous published data. A low proportion of patients had chronic diarrhoea during follow up (7.6%). Conclusion: NP-­‐C disease characteristics were in line with previous publications. Disability status was improved or stable in the majority of miglustat-­‐treated patients. PP4.1 -­‐1595 X-­‐linked adrenoleukodystrophy in childhood Kim EY, Park JH, Kook H and Woo YJ. Department of Pediatrics, Kwangju Christian Hospital, Chonnam National University Medical School, Gwangju, Korea -­‐ [email protected] Purpose: X-­‐linked adrenoleukodystrophy(ALD) is a rare disorder that shows a great deal of phenotypic variability. We subdivided chidhood X-­‐ linked ALD patients into several phenotypes by the age at onset, the sites of most severe clinical involvement and the rate of progression of neurologic symptoms. Methods: Fourteen patients who had been diagnosed as X-­‐ linked ALD and followed up for at least one year were enrolled from 1996 to 2010. Results: 1. Eleven had childhood cerebral ALD, who showed first neurologic symptoms at 7.29 years and progressed rapidly: interval between first symptoms and vegetative state was 1.48 years, and interval from initial symptoms to death was 3.44 years. Treatment with Lorenzo's oil did not prevent neurologic progression. Two patients who underwent umbilical cord blood transplantation died. 2. Two had adolescent cerebral ALD. They had first symptoms at 11.5 years, and showed tendency to progress less rapidly than childhood cerebral form patients. 3. One "Addison only" patient who had adrenal insufficiency without nervous system involvement remained asymptomatic during Lorenzo's oil treatment. 4. Most cerebral form patients except two showed the lesions in both parieto-­‐ocipital white matter in brain magnetic resonance imaging. Conclusion: The cerebral ALD was the most common form in childhood and was asoociated with a grave prognosis. PP4.2 -­‐1916 The clinical, biochemical and molecular characterisation of a UK patient with Salla disease. A case report Venkata NKP, Fry AE, van der Knaap MS, Scully R, Neal JW, Gibbon FM. Department of Paediatric Neurology, University Hospital of Wales, Cardiff, United Kingdom -­‐ [email protected] Salla disease is a rare autosomal recessive neurodegenerative disorder caused by mutations in the SLC17A5 gene. Salla disease (referring to the area of northeast of Finland where it was first described) has rarely been reported outside of Finland, where the p.R39C founder mutation leads to increased incidence. We report a UK patient with confirmed Salla disease. This male patient was the first child of non-­‐consanguineous white British parents. He presented in infancy with speech and motor delay (sitting 1 year, walking 4 years). The patient subsequently developed ataxia, spastic paraparesis and generalised dystonia. At the age of 12 years he developed severe startle seizures and absences. The patient’s EEG was particularly abnormal with high amplitude spike wave discharges. He is now 14 years-­‐old and can speak in simple sentences, finger feeds and dress with assistance. Repeated MRI brain scans showed almost complete absence of myelination of the cerebral white matter, reduced width of the cerebral mantle, thin corpus callosum and atrophic cerebellum. Cerebrospinal fluid analysis revealed an elevated level of N-­‐acetylaspartylglutamate but sequencing of the PLP1 gene was normal. Thin layer chromatography of the patient’s urine demonstrated increased sialic acid excretion. Electron microscopy of a skin biopsy from the patient revealed Schwann cells containing intracytoplasmic inclusions. Cultured skin fibroblasts generated a 6 fold increase in free sialic acid. Sequencing of the SLC17A5 gene showed the patient was a compound heterozygote for two mutations: a previously-­‐reported 5 amino-­‐acid deletion (c.802_816del15; p.Ser268_Asn272del) and a novel missense mutation (c.116G>A, p.R39H). Analysis of maternal DNA confirmed that the changes were on different chromosomes. This case highlights Salla disease as a rare cause of leukodystrophy, which needs considered even in patients without a Finnish heritage. PP4.3 -­‐1921 Outcome of modified Atkins diet in GLUT-­‐1 patients in Western Sweden Michael E, Darin N. Sweden -­‐ [email protected] 71 Objective: Glucose transporter protein-­‐1 deficiency (GLUT-­‐1) is a neurological disorder caused by mutations in SLC2A1-­‐gene leading to a transport defect of glucose over the blood-­‐ brain barrier. Our aim with this study is to report the broad spectrum of signs and symptoms associated with the disease in childhood and report the effects of treatment with a Modified Atkins diet (MAD). Methods and material: There are 7 childhood patients with genetically confirmed GLUT-­‐1 deficiency syndrome in Western Sweden. All are treated with MAD. We have retrospectively studied their medical journals. The effect of MAD was followed using a Clinical Research Form with clinical follow-­‐up after 1, 3, and 6 months as well as after 1 and 2 years. Results: Two patients are recently diagnosed, one of which has been on MAD for 1 month and the other is due in May 2013. The remaining patients have been treated for at least 2 years. All patients presented with epileptic seizures, most had motor deficits (4/7), developmental delay (5/7) and attention deficits (4/7). Two had microcephaly, one had exercise-­‐induced dyskinesia and four experienced worsening on fasting. Age of onset was below 2 years of age in the majority. The median CSF-­‐glucose level was 1.9 mmol/L (Range: 1.5-­‐2.2) and the median blood/CSF glucose-­‐ratio was 0.3(Range: 0.28-­‐0.43). Modes of inheritance were sporadic (3/7), autosomal-­‐dominant (1/7) and gonadal-­‐
mociasm in 3 siblings. Effects of MAD were a complete disappearance of epileptic seizures and discontinuation of medication (5/5), considerable improvement of the motor deficits (3/5) and improvement of the psychomotor development (5/5). Side-­‐effects were generally mild. Conclusion: GLUT-­‐1 deficiency syndrome has a broad clinical phenotype. Due to lack of awareness, the median of doctor’s delay before diagnosis is 2.3 years (range 0.1-­‐14.5 years). MAD is an effective treatment with few side-­‐effects, irrespective of age or combination of symptoms. PP4.4 -­‐1584 The Neuronal Ceroid Lipofuscinoses in Flanders, Belgium Keppens K, Peirens G, Standaert L, Mattheeuws S. De Kade, Spermalie Bruges, Belgium -­‐ [email protected]­‐spermalie.be The neuronal ceroid lipofuscinoses (NCL) are a group of extremely rare inherited neurodegenerative lysosomal storage diseases who can be defined as: “… progressive diseases of the brain and, in most cases, the retina in association with intracellular storage material that is morphologically characterized as ceroid lipofuscin…”. The new classification is based on genetic findings (CLN1-­‐CLN14). In Belgium we lack epidemiological information and a standardized approach. Objectives Starting from the available individual and demographic data, we aim to evolve towards a standardized multidisciplinary approach. This can facilitate early diagnosis and better support for all concerned. Materials and methods In this retrospective study, data from the medical files of patients who resided in Ganspoel or Spermalie are included. These are the 2 specialized institutes for the education of the visually impaired in Flanders. “Contactpunt NCL”, a patient support group, provided some extra info. Seen its predominance, we focused especially on the juvenile form. Results The data of 21 patients with NCL, born between 1964 and 2004, were revised. Early visual failure due to retinal dystrophy was the presenting symptom in all patients. Interval between symptoms and diagnosis was longer than 1 year in 13 cases. Before 1990 diagnosis consisted on the detection of vacuolised lymfocytes and electron microscopic investigation. After this date DNA-­‐analysis was performed. Other parameters were checked: epilepsy, geographical spread, survival rates, death causes. Conclusions Early visual failure is a specific presenting symptom. Although diagnosis is facilitated through genetic testing, the delay between onset of symptoms and final diagnosis is still (too) long. We are convinced that increased awareness, structural measures (register, reference centre, multidisciplinary cooperation) and a standardized approach can lead to less delay in diagnosis, offer better support and service for the patients and next of kin and eventually can be a stimulus for research initiatives. PP4.5 -­‐1813 Nonclinical development of rhTPP1 enzyme replacement therapy for NCL2 Vuillemenot BR, Kennedy D, Katz ML, Coates JR, Lobel P, Tsuruda LS, Henshaw J, Musson D, Keve S, Cahayag R, Tiger P, O'Neill CA. BioMarin Pharmaceutical Inc., California, USA -­‐ [email protected] Neuronal Ceroid Lipofuscinosis, type 2 (NCL2) is caused by lack of tripeptidyl-­‐ peptidase I (TPP1) enzyme activity. Patients accumulate CNS lysosomal storage materials and exhibit progressive neurodegeneration and resulting loss of cognitive, motor, and visual functions, typically beginning by age 4. Death typically occurs by early adolescence. BioMarin is developing recombinant human (rh) TPP1 enzyme replacement therapy. To bypass the blood-­‐brain barrier and facilitate CNS distribution, the enzyme will be administered by intravcerebroventricular (ICV) infusion to the cerebrospinal fluid (CSF). The nonclinical assessment of rhTPP1 evaluated the pharmacology, pharmacokinetics, and safety in disease and normal animal models after CNS delivery. The pharmacodynamic profile was assessed in two NCL2 disease models, the Tpp1-­‐knockout mouse and TPP1-­‐null Dachshund, which recapitulate many aspects of the human disease. In these disease models, administration of rhTPP1 resulted in a 72 reduction of lysosomal storage, attenuation of clinical decline, improvement of cognitive and motor function, and lifespan extension compared with vehicle treated controls. CSF and plasma pharmacokinetics, as well as CNS distribution, were assessed after administration to cynomolgus monkeys and Dachshunds. Peak CSF exposure after ICV infusion was 100-­‐ to 1000-­‐fold higher than that in plasma and remained above the lysosomal Kuptake for 2-­‐3 days post-­‐ dose. The administered rhTPP1 distributed widely in the brain resulting in concentrations 2-­‐ to 10-­‐fold greater than the endogenous wild-­‐type level in many sites. ICV administration resulted in an expected delivery device related inflammation along the catheter track in all animals, including vehicle treated controls. Mild to moderate anaphylactoid reactions observed after repeat dosing in Dachshunds were mitigated by increasing the duration of the infusions and administration of diphenhydramine. The positive nonclinical pharmacology and safety profiles of rhTPP1 offer promise for the planned first in human clinical trial of ICV administered rhTPP1 in NCL2 patients. PP4.6 -­‐1784 S-­‐adenosylmethionine and S-­‐adenosylhomocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation Hagebeuk E, Duran M, Abeling NG, Vyth A, Poll-­‐The BT. Department of Pediatric Neurology, Academic Medical Center, The Nederlands -­‐ [email protected] Objective: Rett syndrome is a neurodevelopmental disorder characterized by cognitive and locomotor regression and stereotypic hand movements. The disorder is caused by mutations in the X chromosomal MECP2 a gene encoding methyl CpG-­‐ binding protein. It has been associated with disturbances of cerebral folate homeostasis, as well as with speculations on a compromised DNA-­‐methylation. Folinic acid is the stable form of folate. Its derived intermediate 5-­‐MTHF supports the conversion of homocysteine to methionine, the precursor of S-­‐ adenosylmethionine (SAM). This in turn donates its methyl group to various acceptors, including DNA, thereby being converted to S-­‐adenosylhomocysteine (SAH). The SAM/SAH ratio reflects the methylation potential. The goal of our study was to influence DNA methylation processes and ameliorate the clinical symptoms in Rett syndrome. Methods: We examined the hypothesis that folinic acid supplementation, besides increasing cerebrospinal fluid (CSF) 5-­‐MTHF (p  =  0.003), influences SAM and SAH and their ratio. In our randomized, double-­‐
blind crossover study on folinic acid supplementation, ten female Rett patients received both folinic acid and placebo for 1 year each. Results: It was shown that both SAM and SAH levels in the CSF remained unchanged following folinic acid administration (p  =  0.202 and p  =  0.097, respectively) in spite of a rise of plasma SAM and SAH (p  =  0.007; p  =  0.009). There was no significant change in the SAM/SAH ratio either in plasma or CSF. Conclusion: The apparent inability of Rett patients to upregulate SAM and SAH levels in the CSF may contribute to the biochemical anomalies of the Rett syndrome. Our studies warrant further attempts to promote DNA methylation in the true region of interest, i.e. the brain. PP4.7 -­‐1709 Aspartylglucosaminuria in a non-­‐finnish patient: a case report Garcia Puig M, Delgadillo Chilavert V, Roche Martínez A, Fernández Zurita C, Escofet Soteras C, Lorente Hurtado I. Department of pediatric neurology. Hospital Parc Taulí Hospital, Sabadell (Barcelona) Spain -­‐ [email protected] Introduction: Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disease due to a defect in the AGA gene, which abolishes the activity of the aspartylglucosaminidase (AGA) enzyme. The most characteristic feature is progressive mental retardation. AGU is estimated to affect 1 in 18,500 people in Finland, this condition is much less common outside of Finland. Clinic case: A-­‐6-­‐year old boy, was visited because of learning difficulties, delay speech and clumsiness. His parents were not consanguineous. He was the product of a full-­‐term pregnancy with normal delivery. Though apparently normal at birth, their development milestones were slow. Physical examination showed language difficulty and clumsiness. Neuropsychological testing revealed IQ scores in the lower limit of the normality. Complementary test included: Karyotype, X-­‐fragile: normal; Brain MRI: cerebellar atrophy. Blood Metabolic screening (lactate, pyruvate, ammonia, amino acids, congenital disorder of glycosylation) and Urinary metabolic screening (amino acid, organic acid, mucopolysacharides , creatine deficiency study, purines): normal; MLPA Subtelomeric analysis: normal In childhood the patient learned new skills abnormally slowly. Mean IQ on WISC-­‐IV scale (10y): 73. From 14 years old he showed slight deterioration of both cognitive and motor skills, and behavioral changes. IQ on WISC-­‐IV scale (14y): 55. Complementary test to rule out neurological progressive disease were performed; brain MRI remained stable; electromyoneurographic, ophtalmological and cardiac examination, abdominal ultrasound were normal. Urinary oligosaccharide analysis detected an abnormal excretion of aspartylglucosamine. Assay for AGA enzyme in fibroblasts reveal a very low activity, establishing a definitive diagnosis of AGU. Conclusions: Clinical diagnosis of AGU is difficult; the initial presentation may be subtle and signs may be variable, resulting in frequent delays in 73 diagnosis. The main signs and symptoms are progressive mental retardation, facial dysmorphism, connective-­‐
tissue involvement and psychiatric problems. Biochemical detection is easy by urine chromatography. No specific therapy is available. PP4.8 -­‐1602 Neonatal onset of a Canavan disease in a Lybian non jewish ashkenazi patient Lakhdhar I, Nagi S, Miladi N. National Institute Mongi Ben Hamida of Neurology La Rabta 1007, Tunis, Tunisia -­‐ [email protected] Neonatal onset of a Canavan disease in a lybian non -­‐jewish ashkenazi patient Canavan disease is a genetic neurodegenerative disease caused by mutations in the ASPA gene. Important clinical features are macrocephaly, hypotonia, head lag and developmental delay. Patients show elevated urinary concentrations of NAA. We reported here a case of an eight month and a half year old girl, born to related Lybian non-­‐Jewish parents, from complicated pregnancy (eclampsia) and without perinatal risks, brought to our department for the etiologic diagnosis of severe developmental delay . The neurological exam shows total absence of psychomotor development with central hypotonic syndrome and slight spasticity of the lower extremities with bilateral Rossolimo sign and important macrocephaly. Epileptic seizures were not yet expressed in the infant. MRI findings shows a hyperintense T2 signal interesting bilaterally and symmetrical all subcortical white matter, and periventricular regions with U fibres involvement and a bilateral signal abnormalities in thalamus and pallidum . Proton magnetic resonance spectroscopy of the brain shows an increase in the concentration of N-­‐acetylaspartic acid (NAA). Although it is a panethnic disease, information on affected individuals in populations of Non-­‐
Ashkenazi Jewish origin is rather limited. Ongoing research aims at a better understanding of Canavan disease and underlying mechanisms as a basis for new therapeutic approaches. PP4.9-­‐1616 Tay-­‐Sachs Disease in a Turkish Patient due to c.78G>A HEXA Mutation: A Case Report Arslan M, Ünay B, Vurucu S, Gül D, Akýn R. Department of Pediatric Neurology, Gülhane Military Medical School, Ankara, Turkey -­‐ [email protected] Tay-­‐Sachs disease (TSD) is an autosomal recessive, neurodegenerative disorder caused by intralysosomal storage of the GM2 ganglioside, resulting from deficient β-­‐hexosaminidase A activity due to β-­‐hexosaminidase α-­‐subunit (HEXA) mutations. TSD has been reported in children of virtually all ethnic, racial, and religious groups. Tay–Sachs disease used to be prevalent (1 in 3900 live births) among Ashkenazi Jews but heterozygote screening and counseling programs led to a 90% reduction of the disease in this high-­‐risk population. At least seven different mutations were identified in Turkish Tay-­‐ Sachs patients to date. This report describes the first Turkish Tay-­‐Sachs patient with c.78G>A (p.W26X) HEXA mutation. Friday 27 September 2013 PP5 Varia (sleep, oncology, trauma) Richard Newton Trauma PP5.0 -­‐1888 Retinal hemorrhages in a university hospital: not always abusive head injury Mattheij M, Venstermans C, de Veuster I, Peerenboom K, Kenis S, Vanderstraete I, Ceulemans B. University Hospital Antwerp, Belgium -­‐ [email protected] Objectives Studies have shown that retinal hemorrhages (RH) and subdural hematomas (SDH) are frequently seen in the presence of shaken baby syndrome (SBS). Many authors state that presence of RH is a pathognomic finding to diagnose SBS. According to our experience, this assumption is incorrect. We performed a retrospective study on children admitted to our university hospital with RH. Material and methods Our study included 29 children with RH, aged 1-­‐18 months old, admitted to our hospital from the year 2000 to 2013. Story and physical examination during presentation, medical course, coagulation tests, metabolic investigations, skeletal survey and head circumference of the infant and his parents were collected. Retinal findings as well as central imaging (CT and MRI) were reassessed to obtain a standardized description. Evaluation reports by social services or civil/criminal courts were collected. (Preliminary) Results Of the 29 children, 23 were found suspect of SBS by the medical team and/or social services. In 5 of the 23 cases shaking was admitted. Three cases showed intraparenchymal hematomas, 4 interhemispheric blood, 4 cerebral edema, 6 compression of a ventricle, and 3 papilledema. In 15 of the 23 cases diffusion-­‐ weighted MRI was performed: 6 showed diffuse lesions, 4 showed 74 bilateral lesions. In 2 of the 6 non-­‐suspect cases a clear etiology was found (accidental trauma or cerebral aneurysm). None of the 4 remaining cases showed intraparenchymal or interhemispheric blood, cerebral edema, compression of a ventricle, diffuse lesions on diffusion-­‐weighted MRI or papilledema. Three of the 4 cases showed an accelerated growth of the head circumference months before presentation. Conclusion According to our study infants can present RH and/or SDH without SBS. Infants with a large head circumference could be predisposed to retinal or subdural hemorrhages with or without a minor trauma. PP5.1 -­‐1846 Pediatric TBI: acute and 1-­‐year MRs/DTI findings Holshouser BA, Ghosh N, Tong KA, Pivonka-­‐Jones J, Rundquist M, Ashwal S. Departments of Radiology and Pediatrics, Loma Linda University School of Medicine, USA -­‐ [email protected] Objective: We present longitudinal MR spectroscopic and DTI findings in children with complicated mild/severe TBI. Methods: Studies were done (7-­‐15 days & 1 year) with MRI (3D-­‐T1W, 3D-­‐T2W, FLAIR, SWI, DTI-­‐mean FA, ADC, AD, RD) and with 3D MRSI (10 mm slabs-­‐corpus callosum-­‐-­‐brain stem). MRSI voxel data were overlaid onto DTI white matter (WM) data to compare DTI parameters to metabolite ratios (NAA/Cr, NAA/Cho, Cho/Cr) for each voxel and region. Neuropsychological evaluations were done (3, 12 months). Results: We studied 17 TBI (13.2yrs; GCS: 3-­‐15) and 15 controls (11.5 yrs). Initial MRI found decreased NAA/Cr and NAA/Cho ratios in all regions in TBI patients compared to controls. Mean FA values were decreased in corpus callosum (CC), basal ganglia (BG), parieto-­‐occipital and temporal white matter. The mixed model analysis which accounts for age effects, showed a significant recovery of NAA/Cr only in 3 regions -­‐ BG (p=0.01), temporal gray (p=0.03) and thalami (p=0.01) and showed no significant longitudinal recovery of DTI metrics compared to controls. The initial NAA ratios and mean FA measurements correlated significantly with IQ and memory deficits evaluated at 12 months after injury. Conclusions: Early decreases in NAA represent neuronal loss or dysfunction and early FA reductions represent structural white matter injury. At 12 months, MRS showed significant recovery of metabolite ratios only in 3 regions, whereas, no regional DTI metrics recovered. This suggests incomplete metabolic and axonal recovery as the source of cognitive impairment. PP5.2 -­‐1844 Advanced MR and spectroscopic imaging in adolescents with chronic post-­‐concussive symptoms following sports-­‐related concussion Bartnik-­‐Olson BL, Grube M, Wang H, Wong V, Holshouser BA, Ashwal S. Departments of Radiology and Pediatrics, Loma Linda University Medical Center, USA -­‐ [email protected] Objective: There is growing interest in using advanced MRI techniques (diffusion tensor imaging, DTI; perfusion weighted imaging, PWI) to identify and quantify microstructural axonal injury and perfusion abnormalities in adolescents with sports related concussion (SRC). We investigated these changes in a group of post-­‐concussive symptomatic adolescents. Methods: We studied 13 adolescents (16± 4 years) who sustained a SRC (1–24 months before imaging) and 14 controls (15± 4 years). Symptoms included headache (persistent or intermittent, n=13), dizziness (n=3), and cognitive (n=6) or behavioral changes (including depression, n=4). DTI and PWI data were acquired on a Siemens Tim Trio 3T scanner. Region of interest DTI (FA, MD, RD) and PWI (CBF, CBV, MTT) analysis was performed. Results: FA and RD were reduced in the genu of the corpus callosum in SRC subjects compared to controls (p=0.05 and p=0.04). SRC subjects also showed reduced rCBF (p=0.03) and rCBV (p=0.05) in the right thalamus and a trend (p=0.06) towards reduced rCBF and rCBV in the left thalamus. Conclusions: Lower callosal FA values have been reported after mild TBI and indicate axonal injury. Elevated RD in this region suggests the presence of myelin damage along with axonal injury. rCBF and rCBV also were reduced in the thalami of SRC subjects and may be due to post-­‐injury vascular disruption or impairment of microvascular responsiveness. Our findings suggest that DTI and PWI reflect different components of the complex injury that occurs after SRC and that both are sensitive indicators of lasting injury in chronically symptomatic athletes. PP5.3 -­‐1676 The risk factors of severe brain injury by head trauma under 6 years old children Na YH, Cha BH. Wonju Severance Christian Hospital, Korea -­‐ [email protected] Objectives: The head trauma is common type of injury coming to emergency room during childhood period, especially under 6 years old children. We would like to evaluate the risk factors of severe brain injuries associated with the head trauma occurring under 6 years old children. Materials and Methods : We retrospectively reviewed the medical records of 392 children, who came to emergency room of Wonju Severance Christian Hospital from March, 2011 to February, 2012 due to head trauma. We evaluated the clinical characteristics of these children for risk factors of severe brain injuries. Results : The 1981 children under 15 75 years old came to emergency room due to traumatic injuries. Among them, 554 children (28.0%) had head trauma and 392 children (70.8%) were under 6 years old; under 3 years old, 244 (62.2%) and between 3 and 6 years old, 148 (37.8%). the male and female ratio was 1.65:1. The causes of head trauma were falling down (77.6%), strucken by objects (8.2%), car accident (7.9%) and unknown (6.3%). The most of children (77.1%) were no neurologic symptoms and signs, but there were noted that intracranial hemorrhage was 24 (6.1%); male 58%, skull fracture, 10 (2.6%); male 80%, seizure, 8 (2.0%); male 75%, intracranial hemorrhage with skull fracture, 14 (3.6%); male 71%, and soft neurologic symptoms, 10 (2.6%); male 67%. The younger aged and male children were more prone to severe brain injuries. Conclusions : The head trauma is common during childhood period, especially under 6 years old children. The most of head trauma children are no severe neurological damages but the severe brain injuries such as intracranial hemorrhage are more common to younger and male children. So we should have more close attention to male and younger aged children preventing severe brain injuries by head trauma. PP5.4 -­‐1971 Cognitive and neural characteristics of mathematical difficulties in children with mild traumatic brain injury (TBI) Van Beek L, Ghesquière P, Lagae L, De Smedt B. Parenting and Special Education, Faculty of Psychology and Educational Sciences, University of Leuven, Belgium -­‐ [email protected] Acute and long-­‐term impairments in academic skills have been reported following TBI in children (Johnson et al., 2009). It turns out that mathematics rather than reading or spelling is the most compromised in these children (Ewing-­‐Cobbs et al., 2004). However, a precise characterization of the mathematical difficulties in pediatric TBI is currently unavailable. Extending the existing body of data, the current study aimed to provide a detailed characterization of the mathematical difficulties in TBI at both behavioral and neural levels. Fifteen semi-­‐acute pediatric mild TBI patients were investigated and compared with 15 matched controls. Behavioral data, including measures of numerical processing, arithmetic and working memory as well as neuro-­‐imaging data were collected. Because diffuse axonal injury is common in TBI and might account for the persistent cognitive problems after TBI (Niogi & Mukherjee, 2010), we used Diffusion Tensor Imaging (DTI) to examine microstructure white matter abnormalities in TBI and related these measures to behavioral performance in children with mild TBI and controls. Against the background of the existence of a fronto-­‐parietal network that is consistently active during calculation tasks (Arsalidou & Taylor, 2011), we investigated fronto-­‐parietal white matter connections and their association with performance on the administered behavioral measures. More specifically, we used DTI tractography to delineate the left Arcuate Fasciculus (AF) that connects frontal and temporo-­‐parietal regions that are active during arithmetic. Preliminary data confirm the specific association between arithmetical competence and fractional anisotropy in the left AF. Data are currently being analysed and we will be able to make conclusions on whether a fronto-­‐parietal white matter deficit can be found in children with mild TBI who have arithmetical difficulties. PP5.5 -­‐1845 Acute and 1 year susceptibility-­‐weighted MRI of hemorrhagic shearing injury after pediatric TBI Tong K, Al-­‐Ramadhani R, Rundquist M, Pivonka-­‐Jones J, Holshouser BA, Ashwal S. Departments of Radiology and Pediatrics, Loma Linda University School of Medicine, USA -­‐ [email protected] OBJECTIVE: MRI susceptibility-­‐weighted imaging (SWI) accentuates paramagnetic properties of blood products and depicts more hemorrhagic brain lesions after traumatic brain injury (TBI) than conventional MRI. We present initial/1 year SWI data in 17 pediatric TBI patients. METHODS: Hospitalized pediatric patients with moderate/severe TBI (GCS score <13 or intracranial injury on CT scan) underwent MRI acutely (7-­‐17d post TBI) and at 1 year. SWI was analyzed using an off-­‐line post-­‐processing program, "SPIN", to semi-­‐automatically count and measure the volume of lesions. The number/volume of lesions between the initial and one year study were compared and correlated with initial injury and gender. RESULTS: We studied 17 patients (6-­‐17 yrs;12 males; 13-­‐
motor vehicle, motorcycle, ATV or pedestrian accidents; 4 falls).The number of SWI lesions/patient on the initial MRI ranged from 0 to 299.The number/volume of hemorrhages on the acute MRI did not correlate with the initial GCS score. By 1 year, the number (up to 81.3%) and volume (up to 84.5%) of hemorrhages decreased. Surprisingly, 9/17 patients retained more than 50% of the original hemorrhagic volume. We did not observe gender differences in resolution of the number/volume of hemorrhages. CONCULSIONS: About 50% of moderate/severe TBI patients have persistent SWI hemorrhagic lesions 1 year after injury. There was no association in degree of hemorrhage resolution with gender or initial GCS. Further analysis will determine if there are regional differences in the resolution or persistence of hemorrhages, correlation with other clinical and imaging variables, associations with lesion location or specific neurological/neuropsychological outcomes. 76 Sleep PP5.6 -­‐2044 Methylphenidate in children with narcolepsy/cataplexy Pons van Dijk G, Jansen K, Lagae L, Buyse G. University Hospitals Leuven, Belgium -­‐ [email protected] Introduction: Narcolepsy-­‐cataplexy is an uncommon sleep disorder that can present in childhood. There is little experience with modafinil in pediatric narcolepsy due to limited efficacy/safety data. Methods: We retrospectively evaluated efficacy and safety of methylphenidate therapy in all pediatric narcolepsy (with or without cataplexy) patients followed at our institution between 2003 and 2013. Results: We identified 13 children with narcolepsy (age of presentation 6-­‐15 years), of whom 3 had secondary narcolepsy. Three patients were excluded because of medical follow-­‐up elsewhere. In the group of primary narcolepsy (age of presentation 6-­‐11 years), 4/7 responded favorable on methylphenidate. Three of them had cataplexy. Excessive daytime sleepiness (EDS) improved in all, cataplexy improved in 2/3, and in 1 additional medication was needed for night terrors. Total follow-­‐up duration was 3 to 10 years. From the three who used modafinil, one switched to modafinil because EDS did not respond enough to methylphenidate, one switched because he reached the age of 18 and from that age modafinil is reimbursed in Belgium. The third never tried methylphenidate because parental refusal. Two of them also had cataplexy and they had a total follow-­‐up of 4 to 7 years. In one EDS improved only partially, cataplexy improved in both partially and 1/4 needed additional medication for night terrors. The 3 children with secondary narcolepsy (age of presentation 10-­‐15 years) responded well on methylphenidate. The causes were craniopharyngioma (1) and pilocytic astrocytomas (2), with a follow-­‐up duration of 2 to 3 years. Two of them also showed cataplexy. All aspects of narcolepsy improved with methylphenidate. Overall, 7/10 responded well on methylphenidate without any significant side-­‐effects. Conclusion: Whereas modafinil is the first choice drug option in adults with narcolepsy with or without cataplexy, our findings suggest that methylfenidate is an effective and well tolerated treatment in pediatric patients. Oncology PP5.7 -­‐1954 Long-­‐term outcome in children with lowgrade tectal tumors and acquired obstructive hydrocephalus Aarsen FK, Arts WFM, Van Veelen-­‐Vincent ML, Lequin MH, Catsman-­‐Berrevoets CE. Erasmus University Hospital-­‐
Sophia Children's Hospital, The Netherlands -­‐ [email protected] Objective: To study long-­‐term neurologic, cognitive and behavioral deficits in children with a low grade tectal tumor and acquired obstructive hydrocephalus. Method : In a consecutive series of 12 children with low-­‐grade tectal tumor diagnosed in our hospital neurologic, neuropsychologic, and radiologic data were prospectively collected. Intelligence, memory, attention, language, visual-­‐spatial, and executive functions were assessed. Follow-­‐up ranged from 1 year to 10 years. Results: At follow-­‐up, most frequent neurologic disability was fatigue in children with a low-­‐grade tectal tumor. They scored lower on sustained attention, long-­‐term memory and had more behavioral problems. Factors influencing cognition were duration of symptoms of raised intracranial pressure and persisting severe hydrocephalus. The cognitive problems resulted in 60% of children needing assistances of special services at school. Conclusion: At long-­‐term, children with a low-­‐grade tectal tumor display invalidating neuropsychologic impairments due to compression of supratentorial structures in the cerebello-­‐
cortical circuitry by the obstructive hydrocephalus resulting in educational problems. Adequate and timely treatment of hydrocephalus may result in better cognitive functioning. Neuropsychological findings in children with tectal glioma and obstructive hydrocephalus are very similar to findings in children with the cerebellar cognitive affective syndrome after cerebellar tumor surgery. This suggests that at least part of this syndrome in children after cerebellar tumor surgery is caused by the effects of obstructive hydrocephalus. PP5.8 -­‐1542 Vincristine induced neuropathy in Children with Acute Lymphoblastic Leukemia -­‐ Prevalence and Electrophysiological Characteristics Puneet Jain, Sheffali Gulati, Rachna Seth, Sameer Bakhshi, GS Toteja, Ravindra Mohan Pandey. Division of Pediatric Neurology, AIIMS, Delhi, India -­‐ [email protected] Objectives: With better survival rates in childhood acute lymphoblastic leukemia (ALL), the focus is increasing on the late effects of treatment and ways to monitor and prevent them. The prevalence of vincristine induced neuropathy have been poorly documented in childhood ALL survivors. The aim of the current study was to assess the prevalence of neuropathy (clinical and electrophysiological) in a cohort of childhood ALL patients > 5 years of age who had completed their chemotherapy regimen. Methods: This cross-­‐sectional study was carried out in the Departments of Pediatrics and Medical oncology at a tertiary care centre in North India from October 2011 to 77 June 2012. After obtaining the ethical clearance, 80 consecutive children, meeting the inclusion and exclusion criteria, were enrolled. Informed written consent was taken. Detailed nerve conduction studies were performed and Reduced version of Total Neuropathy Score (TNSr) was calculated. Results: 80 consecutive children were enrolled. The mean age at the time of evaluation was 11.2 ± 3.2 years. The children on average were 20.5 ± 11.8 months post-­‐chemotherapy. The mean interval between the VCR injection and evaluation was 20.6 ± 11.8 months (3-­‐39 months). The mean cumulative VCR dose during the treatment was 25.8 ± 9.3 mg. Around 13.8% children had clinical evidence of peripheral neuropathy. Twenty-­‐seven children (33.75%; 95% CI: 23.6-­‐45.2%) had peripheral neuropathy electrophysiologically. Symmetric motor axonal polyneuropathy was the most common pattern of involvement with common peroneal nerve most commonly involved. Twenty-­‐seven children (33.75%) had TNSr score ≥ 1. Conclusions: Neuropathy may be a long term adverse effect of VCR rather than being limited to acute neurotoxicity during therapy. Neuropathy may persist despite stopping VCR therapy. Thus, early detection of neuropathy and dose alteration of VCR is important during chemotherapy. Varia PP5.9 -­‐1991 Effect of hypothyreosis on the developing chick cerebellum Larsen SM, Aden P, Paulsen RE, Goverud IL. Oslo University Hospital, Dept. of Clinical Neurosciences for Children and University of Oslo, Norway -­‐ [email protected] Objectives: Brain development in humans is a complex process needing optimal environment in utero, good health and nutritional level of the mother so that processes such as cell proliferation, programmed cell death, and migration are timed correctly. Thyroid hormones play a pivotal role in these processes but detailed mechanisms are still unknown. Materials and Methods: We have used a chicken embryo model to test hypothyreosis in the developing cerebellum, by injecting the thyreostatic drug methimazole into eggs on embryonic day 14 (E14), and then sacrificing the embryos on E17 and E19. Investigation of cell proliferation was done by BrdU labeling, injected 3 h before sacrifice. Morphological cell death was quantified in HE microscopy. Western blot has been used to investigate migration of granule neurons measuring the level of PAX6 protein as marker. Results: Our results showed that cell proliferation was physiologically reduced during this period. Similar tendencies were seen in mild and severe hypothyreosis (BrdU). Programmed cell death or apoptosis is physiologically reduced in this period. Our study shows that mild hypothyreosis delayed this process in this period, and severe hypothyreosis probably even more. Western blot showed a tendency to physiological reduction in expression of PAX6 protein in this period. Expression of PAX 6 in severe hypothyreosis increased rather than decreased. Conclusions: Lack of thyroid hormone delays cell death, and results in changes in migration marker PAX6, suggesting that cerebellum may be a target for hypothyreotic neurotoxicity. PP6 Neurogenetic and mitochondrial disorders Haiki Rantala Neurogenetic PP6.0 -­‐1815 Everolimus for subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis complex (TSC): results from the EXIST-­‐1 trial by age category Jozwiak S, Brechenmacher T, Segal S, Franz DN. The Children's Memorial Health Institute of Warsaw, Poland -­‐ [email protected] Objective: To examine the impact of age on the efficacy and safety of everolimus treatment for SEGAs associated with TSC for patients in the EXIST-­‐1 trial (NCT00789828). This trial previously demonstrated that everolimus was superior to placebo for reducing SEGA volume (P˂0.0001) with a safety profile consistent with previous reports in the TSC population. Materials and Methods: Patients of any age with ≥1 SEGA lesion (≥1 cm in longest diameter) were randomized (2:1) to receive 4.5 mg/m2/day everolimus (titrated to blood trough levels of 5-­‐15 ng/mL) or placebo. The primary endpoint was SEGA response rate (proportion of patients with ≥50% reduction in sum of volumes of all target SEGAs [≥1 cm in longest diameter] compared with baseline). Skin lesion response rate was one of the key secondary endpoints and was assessed in patients with ≥1 skin lesion at baseline. Adverse events (AEs) were monitored at every visit. The data for everolimus patients aged ˂3 (n=13), ≥3 to 18 (n=55), and ≥18 years (n=10) and placebo patients aged <3 (n=7), ≥3 to 18 (n=26), and ≥18 years (n=6) are reported herein. Results: The SEGA response rate for patients aged ˂3, ≥3-­‐18, and ≥18 years was 23% (95% CI, 5%-­‐54%), 40% (95% CI, 27%-­‐54%), and 50% (95% CI, 19%-­‐81%) for everolimus, compared with 0% (95% CI, 0%-­‐
41%), 0% (95% CI, 0%-­‐13%), and 0% (95% CI, 0%-­‐46%) for placebo. All skin lesion responses were partial (improvement ≥50%-­‐˂100%). For everolimus and placebo, respectively, skin lesion responses were seen in 2/12, 78 31/51, and 5/9 patients and 0/7, 4/25, and 0/6 patients aged ˂3, ≥3 to 18, and ≥18 years, respectively. Conclusions: SEGA and skin lesion responses were observed in all everolimus age categories. The small sample size in some age categories may have limited the results. PP6.1 -­‐2162 Hamartin and tuberin expression studies: further insights into TSC1 and TSC2 genes in a cohort of patients with well defined phenotype Lannoy N, Durant J-­‐F, Corbisier T, Ambroise J, Nellist M, Jansen A, Pelc K, Nassogne M-­‐C, Gala J-­‐L, Lederer D, Vikkula M, Sznajer Y. Centre de Génétique Humaine UCL, Cliniques Universitaires Saint-­‐Luc, Brussels, Belgium -­‐ [email protected] Tuberous sclerosis complex (TSC) represents one autosomal dominant genodermatosis with multisystemic involvement. In 20% of patients with definite TSC diagnosis, point mutation or deletion/duplication either in TSC1/TSC2 genes can’t be identified. Neither other mechanisms nor gene anomalies contribute so far to the cause of TSC. To further evaluate on TSC1 or TSC2 genes involvement in TSC patients, we conduct a distinct expression study. In a cohort of 132 index patients referred with definite, possible or probable TSC diagnosis, 25 (19, 5, 1 respectively) were not found with a deletion or mutation. In two familial presentations segregation was completed as RT-­‐PCR quantification of 24 TSC1/TSC2 mRNA (DNA and RNA from blood samples and from 5 normal and/or abnormal fibroblast cultures). Gene expression modulation was carried out after normalization with β-­‐actin housekeeping gene and with DU145 cell line as qPCR calibrator using the 2-­‐ΔΔCt method. Sequencing of TSC1/TSC2 promoters and flanking 5’/3’UTR regions were studied from DNA of 8 definite TSC patients. In one familial presentation, haplotype segregation identified an association to TSC2 locus. Among the 24 TSC patients -­‐ after validation with healthy controls -­‐ expression studies identify normal, elevated or decreased hamartin or tuberin levels (in one only or both TSC alleles) in 50 % patients of all classified. In one patient, expression studies from pigmented skin revealed abnormal values compared with the normal skin. Decreased TSC2 mRNA value was observed in patient with familial association to TSC2 locus. Any sequence distortion was found in both promoters as in 5’/3’UTR regions of TSC1/TSC2 genes in 4 definite TSC patients presenting expression anomalies. The present results postulate on additional genetic heterogeneity or epigenetic mechanism to possibly explain occurrence for TSC when expression studies were abnormal. In case of normal levels, one or more other genes could be associated with TSC phenotype. PP6.2 -­‐1668 Early EEG monitoring following prenatal diagnosis predicts epileptogenesis in tuberous sclerosis Moavero R, Cusmai R, Vigevano F, Toscano A, Caforio L, Bernardi B. Child neurology and psychiatry unit, Tor Vergata University Hospital, Rome, Italy -­‐ [email protected] Objectives. To describe the role and the usefulness of a close EEG monitoring in children with tuberous sclerosis complex (TSC), following a prenatal diagnosis. Materials and Methods. We present 3 patients with negative familial history, in which the routine fetal ultrasound revealed the presence of multiple cardiac rhabdomyomas. Between 30 and 32 weeks of gestation we performed a fetal MRI, which was able to detect the presence of subependymal nodules or tubers, allowing a definite prenatal diagnosis of TSC. Due to large rhabdomyomas and to the risk of cardiac symptoms, we planned delivery by cesarean section in tertiary centres with experienced neonatal cardiologists. Soon after birth, all these children began a close EEG monitoring, with awake/sleep EEG performed every 3-­‐4 weeks. All the families have been informed of the high risk of epilepsy of TSC infants in the first year of life, and have been educated to recognize focal subtle seizures and epileptic spasms. Results. EEG monitoring allowed us to identify focal epileptiform abnormalities early and to observe their evolution towards multifocal abnormalities. In the child who developed epileptic spasms we observed a further evolution toward secondary bilateral synchronization and a tendency toward a pre-­‐hypsarrhythmic pattern the day before the appearance of spasms. The immediate treatment with vigabatrin early reversed this EEG pattern, and we never observed again abnormalities suggestive of an epileptic encephalopathy. Conclusions. Our data suggests that epileptogenesis is a slow process, taking several weeks or months from the first EEG epileptiform abnormalities to the first seizure. The close EEG monitoring allows us to detect subtle changes in the EEG pattern which might indicate an evolution towards epilepsy. The immediate detection and treatment of seizures is crucial to minimize the possible long-­‐term neurodevelopmental sequelae of early life seizures. PP6.3 -­‐1724 X-­‐linked sideroblastic anemia and ataxia: a fourth family with identification of a novel ABCB7 gene mutation D'Hooghe M, Selleslag D, Mortier G, Van Coster R, Vermeersch P, Billiet J, Bekri S. Department of Neurology and Child Neurology, Hospital Sint-­‐Jan, Bruges, Belgium -­‐ [email protected] 79 X-­‐linked sideroblastic anemia and ataxia (XLSA-­‐A) is a rare cause of early onset ataxia, which may be overlooked due to the usually mild asymptomatic anemia. The genetic defect has been identified as a mutation in the ABCB7 gene at Xq12-­‐q13. The gene encodes a mitochondrial ATP-­‐binding cassette (ABC) transporter protein involved in iron homeostasis. Previously only three families have been reported, each with a distinct missense mutation in this gene. We describe a fourth family with XLSA-­‐A and a novel mutation in the ABCB7 gene. Mutations in this gene should be considered in any unexplained X-­‐linked ataxia, even in the absence of clear hematological changes. The whole blood total erythrocyte protoporphyrin measurement may be used as a screening tool. The precise diagnosis of XLSA-­‐A gives important information about the management, the prognosis and the genetic implications. For many references, see: D'Hooghe M, Selleslag D, Mortier G, Van Coster R, Vermeersch P, Billiet J, Bekri S. X-­‐linked sideroblastic anemia and ataxia: A new family with identification of a fourth ABCB7 gene mutation. Eur J Paediatr Neurol. 2012 Nov;16(6):730-­‐5. doi: 10.1016/j.ejpn.2012.02.003. Epub 2012 Mar 6. PP6.4 -­‐1601 Aicardi-­‐Goutieres syndrome in a Lybian family Lakhdhar I, Turki I, Miladi N. National Institute Mongi Ben Hamida of Neurology La Rabta 1007, Tunis, Tunisia -­‐ [email protected] Aicardi–Goutieres syndrome in a Lybian Family Ines Lakhdhar, Ilhem Turki, Najoua Miladi National Institute Mongi Ben Hamida of Neurology La Rabta 1007 Tunis Tunisia Aicardi-­‐Goutières syndrome (AGS) is a progressive encephalopathy, possibly with a recessive autosomal pattern of inheritance, which has onset in the first year of life and is characterized by acquired microcephaly, basal ganglia calcifications, white matter abnormalities, chronic lymphocytosis in the cerebrospinal fluid (CSF) and raised interferon-­‐alpha (INF-­‐alpha) in the CSF. We report here a case of a seven year old boy, born to healthy, related parents (distant consanguinity), from non-­‐
complicated pregnancy and without perinatal risks, presenting at the age of one month and a half a severe psychomotor regression. The parent’s history revealed similar clinical features on two sisters aged respectively five and one year and a half, and three cousins born to related parents. The neurological exam showed tetraplegia, upper limb dystonic movements, oral-­‐facial dyskinesias, nystagmus and absence of eye contact. Cerebral CT scan showed bilateral and symmetrical calcifications in the cerebellum, the dentate nucleus, basal ganglia and periventricular regions. MRI demonstrated a leukoencephalopathy aspect, calcifications and severe atrophy. Laboratory results (blood and urinary phosphorus and calcium, serum total parathormone, lactate, pyruvate, amino and organic acid chromatography) permitted to exclude common and rare causes of basal ganglia calcifications. TORCH serology was negative. Analysis of the CSF was performed searching increased levels of INF-­‐alpha. AGS is a genetic disease with a severe clinical picture. It can be misdiagnosed as a congenital infection or, unless a brain CT scan is performed, as a leukoencephalopathy of unknown origin. Current studies aiming to clarify the molecular mechanisms underlying the pathogenesis of AGS could lead to the development of new therapeutic strategies. PP6.5 -­‐1922 Incidental findings in array CGH Keymolen K, De Rademaeker M, Van Den Bogaert A. Center for Medical Genetics, UZ Brussel, VUB, Belgium -­‐ [email protected] Array Comparative Genomic Hybridization (array CGH) is nowadays widely used in the diagnostic work-­‐up of intellectual disability, congenital anomalies and psychiatric disorders. In contrast with the standard karyotype, it allows us to pick up microdeletions -­‐ and duplications, thus increasing the number of patients for which the etiology of their problem can be demonstrated. In few cases, the array CGH result also uncovers susceptibility to serious late(r) -­‐ onset disorders, such as hereditary cancer syndromes. Although the risk for such an incidental finding is low, the physician who prescribes the analysis should be aware of this possibility and should inform the patient and / or the parents before the test is undertaken. In case of a parentally inherited aberration, the carrier parent is equally at risk for the concerned disorder and pretesting counseling should address this item too. We will illustrate the possibility of incidental findings on array CGH with two cases. The first patient is an infant with congenital anomalies and severe hypotonia.. Array CGH analysis reveals a 23Mb deletion of 5q22.1q23.1. This region includes the APC gene, responsible for Familial Adenomatous Polyposis. This child will thus require close gastrointestinal follow-­‐up from the age of 10 years on. Since the deletion is de novo, the parents are not at increased risk. The second patient is a girl with bilateral aniridia. She has a 15 Mb deletion on 11p14.1p11.2, encompassing the PAX 6 gene, which explains the ocular phenotype. However, the deletion also includes the WT1 gene, involved in renal neoplasia. Close monitoring allowed the early detection and treatment of a kidney tumor in the child. Conclusion: we want to draw the attention of the prescriber of array CGH to the small but 80 existing risk of incidental findings with important consequences for the patient. Pretest information is therefore mandatory. Mitochondrial PP6.6 -­‐1797 Isolated Complex I Deficiency and Atypical Clinical Courses in Three Patients due to Novel Mutations in NDUFS1 and NDUFV1 Björkman K, Sofou K, Darin N, Kollberg G, Holme E, Tulinius M, Oldfors A, Moslemi AR. The Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Göteborg, Sweden -­‐ [email protected] Objectives: To report three patients with atypical clinical course, to add to our understanding of genotype-­‐
phenotype correlations in genes encoding complex I electron input module subunits. Materials and methods: Three patients with isolated complex I deficiency. One girl, patient 1, who presented at birth with hypotonia and feeding difficulties, and died at 5 weeks of age. Two sisters, patients 2 and 3, who presented at 6-­‐7 months of age with progressive muscle weakness and delayed motor development, and have since showed a mild clinical course with long life span and normal mental development. Results: Metabolic findings indicated isolated complex I deficiency. Molecular genetic analysis showed compound heterozygosity for two novel point mutations in NDUFS1 for patient 1 and compound heterozygosity for two novel point mutations in NDUFV1 for patients 2 and 3. A literature review of all reported cases of mutations in the affected genes (NDUFS1, 12 patients; NDUFV1, 14 patients) showed that the clinical course of these three patients was atypical with regard to other patients described with mutations in corresponding genes. Conclusions: Genotype-­‐phenotype correlations in patients with mutations affecting the genes that encode the electron input module of complex I vary, but patients with NDUFS1 mutation tend to have a shorter life span than patients with NDUFV1 mutation. Even considering this, the reported patients show that atypical clinical courses occur. Identifying the mutations is of importance for accurate genetic counseling. Compund heterozygosity due to the combination of a null mutation and a milder missense mutation may predict a more severe phenotype compared to the combination of two milder missense mutations. PP6.7 -­‐1623 Acute liver failure in patients with POLG1 mutations after valproate exposure and their prognosis after liver transplantation Hynynen J, Komulainen T, Tukiainen E, Nordin A, Arola J, Kälviäinen R, Jutila L, Röyttä M, HInttala R, Suomalainen A, Majamaa K, Mäkisalo H, Uusimaa J. University of Oulu, Oulu University Hospital, Finland -­‐ [email protected] Objectives: Patients with mutations in POLG1 gene encoding the catalytic subunit of mitochondrial DNA polymerase gamma have an increased risk for valproate-­‐ induced liver failure. The role of liver transplantation for patients with mitochondrial diseases has been controversial. We studied the development of valproate-­‐
induced liver failure in patients with POLG1 mutations and the prognosis after possible liver transplantation. Methods: Patients with severe valproate-­‐induced liver failure were retrospectively identified from the register at the Department of Transplantation and Liver Surgery, Helsinki University Hospital, Finland (880 liver transplantations since 1988). Liver transplantation and clinical follow-­‐up had been conducted according to routine procedure. POLG1 was analyzed in blood DNA and the mtDNA content in patient and control liver samples was quantified by using real-­‐time quantitative PCR. Results: Five out of six patients with valproate-­‐
induced liver failure (at 13-­‐34 years) were identified (one patient with reversible liver failure was not studied). Four patients had mtDNA depletion in liver associated with homozygous POLG1 p. W748S and p. E1143G mutations; one being also heterozygous for p. Q497H mutation. One patient had died due to intractable status epilepticus and liver failure without transplantation. Three patients with liver transplant are alive and have survived 4-­‐19 years. One patient has chronic pancreatic insufficiency. Neurological manifestations include ataxia, peripheral neuropathy and occasional epileptic seizures; one patient has been seizure free for 11 years. Furthermore, one patient with a heterozygous POLG1 p. Q1236H mutation without mtDNA depletion in liver died suddenly two years after the liver transplantation. Conclusions: Consistent with the recent finding a heterozygous POLG1 p. Q1236H mutation was related to valproate-­‐induced liver failure without mtDNA depletion whereas patients homozygous for POLG1 p. W748S and p. E1143G mutations have mtDNA depletion. We emphasize that POLG1 gene analysis should be performed for all patients with acute liver failure following valproate treatment. 81 PP6.8 -­‐1911 A complex V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy Jonckheere AI, Renkema GH, Bras M, van den Heuvel LP, Hoischen A, Gilissen C, Huynen MA, de Vries MC, Smeitink JAM, Rodenburg RJT. University Hospital Brussels, Belgium -­‐ [email protected] Objective: Whole exome sequencing is a powerful tool to detect novel pathogenic mutations in patients with suspected mitochondrial disease. However, the interpretation of novel genetic variants is not always straightforward. Here, we present two siblings with a severe neonatal encephalopathy caused by complex V deficiency. The aim of this study was to uncover the underlying genetic defect using the combination of enzymatic testing and whole exome sequence analysis, and to provide evidence for causality by functional follow-­‐up. Materials and methods: Measurement of the oxygen consumption rate and enzyme analysis in fibroblasts were performed. Immunoblotting techniques were applied to study complex V assembly. The coding regions of the genome were analysed. Three-­‐dimensional modelling was applied. Results: Exome sequencing of the two siblings with complex V deficiency revealed a heterozygous mutation in the ATP5A1 gene, coding for complex V subunit α. The father carried the variant heterozygously. At the messenger RNA level, only the mutated allele was expressed in the patients, while father expressed both the wild type and the mutant allele. Gene expression data indicate that the maternal allele is not expressed, which is supported by the observation that the ATP5A1 expression levels in the patients and their mother are reduced to approximately 50%. Complementation with wild type ATP5A1 restored complex V in the patient fibroblasts, confirming pathogenicity of the defect. At the protein level, the mutation results in a disturbed interaction of the α-­‐subunit with the β-­‐
subunit of complex V, which interferes with the stability of the complex. Conclusions: This study demonstrates the important value of functional studies in the diagnostic work-­‐up of mitochondrial patients, in order to guide genetic variant prioritization, and to validate gene defects. PP6.9-­‐1900 Early fatal outcome in two patients with defect in NFU1 Van Coster R, Smet J, De Paepe B, Vanlander A, De Latter E, De Meirleir L, Lissens W, Seneca S. Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Gent, Belgium -­‐ [email protected] Background: Recently, mutations have been detected in NFU1 and BOLA3, two genes involved in iron-­‐sulfur biogenesis. In affected patients, defects in the OXPHOS complexes I and II, in 2-­‐oxoacid dehydrogenase and in lipoate synthesis were found. Objective: The objective was to screen our database of patients to find patients with similar clinical and biochemical findings and to sequence the two genes in suspected patients. Patients and Methods: Patients with encephalopathy, failure to thrive, hyperlactacidemia, increased glycine in cerebrospinal fluid and decreased activities of the complexes I and II were selected. BN-­‐PAGE, western blotting and Sanger sequencing was performed. Results: A decreased protein amount in the complexes I and II was visualized using BN-­‐ PAGE. A decrease of structural subunits in complexes I and II and low signals of protein-­‐bound lipoic acid were detected by western blotting. Mutations were detected in NFU1 in both patients. One patient carried the 'hotspot' mutation p.Gly208Cys and the other was a compound heterozygote for this mutation and for p.Arg21Pro. Conclusion: Only three papers were reported earlier in the literature describing patients with NFU1 deficiency. Our results are concordant with the assumed role of NFU1 in ISC biosynthesis and a novel compound heterozygous mutation is presented here. PP7 Epilepsy 2 PP7.0 -­‐2029 Morphological ECG changes in seizures: implications for seizure detection John Stevenson Jansen K, Varon C, Van Huffel S, Lagae L. Pediatric neurology, University Hospitals Leuven, Belgium -­‐ [email protected] Objectives: Epileptic seizures can influence cardiac function in epilepsy patients. This can change the morphology of the ECG signal during seizures. Seizure detection could reduce morbidity and mortality in epilepsy patients. This study aims to develop a method for seizure detection based on morphological ECG changes during seizures in childhood epilepsy. Materials and methods: ECG segments were selected from recordings of 35 patients admitted to the epilepsy clinic of the University Hospital Leuven. From these recordings, 80 segments of 5 minutes were selected, starting 3 minutes before the onset of 40 partial and 40 generalized seizures. For each 82 segment, a moving window equivalent to 5 heartbeats was shifted with an overlap of 4 heartbeats throughout the whole segment. For each window, a matrix containing the 5 QRS complexes was analyzed using principal component analysis (PCA). The 4th and 5th components were selected as features. These two features, together with the mean RR interval per window, were used to discriminate seizures. Results: The positive predictive value (PPV) of the proposed methodology was 79.17% for partial seizures, which were identified in a 7.4±14.3 seconds range. For generalized seizures, the obtained PPV equals 57.38%, and the time difference was 9.6±20.5 seconds. For both types of seizures, about 75% of the changes in the ECG were lagging the onset in the EEG. Conclusions: Morphological ECG changes can be used to improve seizure detection in partial and generalized seizures in childhood. PP7.1 -­‐1956 Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsy – first European experience Biro A, Stephani U, Tarallo T, Bast T, Kurlemann G, Leiz S, Nikanorova M, Wolff M, Haberlandt E, Selch C, Fiedler A, Staudt M, Kluger G. Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Vogtareuth, Germany -­‐ [email protected] Objectives: Aim of this survey was to explore the effectiveness and tolerability of perampanel (PER) in a heterogeneous group of patients under 18 years of age with refractory epilepsies. Methods: This observational survey was conducted as a collection of retrospective data from multiple centers in Germany, Austria and Denmark. Clinical course of the first patients treated in these centers with PER was documented. Initial dosage and titration schedule of PER were at the discretion of the treating physician according to medical need. Effectiveness was evaluated by comparing the frequency of seizures between baseline and the last 4-­‐week period of observation. Observation is continuous and planned until an 18-­‐month follow-­‐up. Results: The study population consisted of 50 children (mean age: 10,3 years, range: 2-­‐17, male: 22), with various refractory epilepsies classified as focal epilepsy (n=28), generalized epilepsy (n=14), LGS (n=4), Dravet Syndrome (n=2), and others (n=2). The response rate (50% seizure reduction) in the first 3 months of therapy was 26% (13 of 50 patients) in total. Of all patients, 12% (n=6) experienced a 50-­‐75% reduction and 12 % (n=6) experienced a more than 75% reduction in seizure frequency. Complete seizure control was achieved in 2 % (n=1). Adverse events were reported in 24 cases, mostly mild-­‐moderate, with remission spontaneously or with decreasing the PER dosage. The most frequently occurring adverse events were fatigue (n=11), agitation or aggressivity (n=9), dizziness (n=5), and changes in appetite (n=5). Severe adverse events (severe behavioral changes, dizziness, fatigue, headache, diarrhea-­‐vomiting) occurred in 6 cases. Conclusions: These preliminary data suggest that PER may be effective in the treatment of children and adolescents with refractory epilepsies of different etiologies. There is a lack of pharmacokinetic data in young patients, low titration rates may reduce side effects. Longer follow-­‐up of our patients and further investigations are needed. PP7.2 -­‐1886 Do adolescents with epilepsy have adequate knowledge regarding antiepileptic drug treatment? Prpic I, Bezak B. Rijeka, Croatia -­‐ [email protected] Objective: Knowledge and education process regarding drug therapy of epilepsy is very challenging process. So, we investigated general knowledge and sources of information about antiepileptic drug (AED) treatment among adolescents with epilepsy. Methods: Written survey containing 29 questions was administrated among 60 randomly selected adolescents with epilepsy (mean age=14,6 years, mean duration of AED treatment 3,7 years) who attended their ordinary check-­‐up’s on Paediatric Neurology department in University Hospital Rijeka, Croatia. Questions were formed to investigate adolescent’s knowledge towards their illness, their general awareness of drugs and correct usage of AEDs, treatment compliance, and adolescent's main source of education towards their illness and drugs they're using. Parental informed consent was obtained at the beginning of the survey. Results: AED was taken without parental control in 70% of respondents, mostly in those adolescents older than 15 years. 78% of respondents named exact dose of drug that they are using. Questions regarding general drug knowledge were correctly answered in 58%. Additional factors relevant for successful treatment and control of epilepsy were correctly recognized only in 28% of respondents. Child neurologist, parents, and internet were major source of information regarding epilepsy and AEDs treatment. Conclusion: Results regarding knowledge towards AEDs among adolescents with epilepsy are encouraging. However, great majority of adolescents are not aware of additional factors important in decreasing the risk of harm due to seizure and seizure treatment (regular sleep, alcohol use, appropriate sport activities). Furthermore, in process of reducing and avoiding harm due to epilepsy and AED treatment among children with epilepsy education 83 should be extended to younger children. Nurses, family physicians and psychologist should be more active members in that process. PP7.3 -­‐1883 Language area organization in children with non-­‐lesional frontal epilepsy Tarta-­‐Arsene O, Preoteasa F, Agavriloaei M, Tarta-­‐Arsene E. Pediatric Neurology Department, Clinica Hospital 'Al. Obregia', Bucharest, Romania -­‐ [email protected] Purpose: It was described that language areas in children with epileptic seizures is different due to neuroplasticity of a developing brain. In this study, it was analyzed through fMRI the features of Broca’s area in children with frontal non-­‐dominant, non-­‐lesional epilepsy and compared with normal children at the same age, in order to find significant differences. Methods: 26 children diagnosed with focal frontal non-­‐lesional epilepsy were analyzed and compared with 25 normal children at the same age. The clinical features related to epileptic seizures were analyzed. All subjects had morphological cerebral MRI in order to exclude a structural lesion in the language area and then they have performed fMRI with specific tasks for activation of Broca area. The results were statistically analyzed and compared with published data. Results: The two groups of subjects were statically comparative considering general data: age, sex, social environment, verbal intelligence coefficient and clinical laterality. The epilepsy’s analysis showed a median period between the onset of epilepsy and fMRI of almost 4 years and median number of seizures 10 (a sufficient period of time and number of seizures for reorganization of cerebral brain area). The EEGs show an active frontal dominant epileptiform discharges in 60% of cases. All children had succeed to follow efficient the tasks for language activation for Broca’s area, and the comparative analyzes showed an abnormal lateralization in epileptic patients, more on the right hemisphere than in normal group (p-­‐0.0327). This aberrant organization was proven to be correlated with onset of seizures below the age of 1 (p-­‐0.0467), presence of status epilepticus (p-­‐0.0424) and treatment with two antiepileptic drugs (p-­‐ 0.0424). Conclusions: This study could be considering as a starting point for the futures studies in evaluation of abnormal language organization of epileptic children. PP7.4 -­‐1876 Contribution of magnetic source imaging to the presurgical evaluation of refractory focal epilepsy in children Badin F, De Tiège X, Op De Beeck M, Van Bogaert P. Department of Pediatric Neurology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium -­‐ [email protected] Magnetic source imaging (MSI) combines magnetoencephalography (MEG) and structural cerebral MRI to estimate non-­‐invasively the source location at the origin of magnetic fields recorded by MEG. To evaluate the contribution of MSI in the presurgical evaluation of refractory focal epilepsy in children, we retrospectively selected 24 consecutive patients aged from 2 to 17 years who benefited from MSI in their presurgical work-­‐up. MEG sources location of epileptic events was determined by conventional equivalent current dipole modeling. We first studied the concordance between MEG sources and the presumed location of the epileptogenic zone (PLEZ) as determined by scalp video-­‐EEG, MRI, and FDG-­‐PET data. In a second step, we correlated the extent of MEG sources resection with post-­‐surgical outcome in patients who underwent respective surgery. This was performed by coregistering MEG sources on postsurgical MRI to assess whether they were located inside or outside the resected cerebral tissue. We found MEG epileptic events in 19 children (79%), and good concordance between the PLEZ and the MEG sources in all of them. Seven children had MEG sources outside the PLEZ. In the subgroup of 9 children who were operated on, the seizure-­‐ free patients (n=8) had 41% of their MEG sources inside the resection, 77% of their sources in the 1-­‐cm extended area, and 96% in the 2-­‐cm extended area. For the only patient who was not seizure-­‐free, these numbers were 5%, 57% and 87%, respectively. In conclusion, MSI added new information to indentify the PLEZ in the presurgical evaluation of this pediatric cohort of refractory epileptic patients. On the other hand, we found that the whole MEG sources resection was not necessary to make the patient seizure-­‐free. The relationship between the extent of resection of tissue containing MEG sources and the post-­‐surgical outcome needs to be prospectively analyzed on a larger population. PP7.5 -­‐1768 Efficacy of long-­‐term adjunctive zonisamide therapy in paediatric patients with partial epilepsy: results of an open-­‐label extension study of a Phase III, randomised, double-­‐blind, placebo-­‐controlled trial Rosati A, Giorgi L, Bradshaw K, Guerrini R. Neuroscience Department, Children’s Hospital Anna Meyer-­‐University of Florence, Florence, Italy -­‐ [email protected] Objectives: To assess the long-­‐term efficacy of once-­‐daily adjunctive zonisamide therapy in paediatric patients with partial epilepsy. Materials and Methods: An open-­‐label extension study of a Phase III, double-­‐blind, randomised, placebo-­‐controlled, multicentre trial was conducted in patients (age 6-­‐18 years) with partial 84 epilepsy receiving one or two antiepileptic drugs (AEDs). Study began with a double-­‐blind transition period (duration 2-­‐11 weeks), during which patients already receiving zonisamide continued at same dose, while those previously receiving placebo switched to zonisamide, initiated at 1 mg/kg/day and up-­‐titrated to a target of 8 mg/kg/day (maximum 500 mg/day). This was followed by an open-­‐label period (duration 45-­‐57 weeks), during which zonisamide dosing could be adjusted according to tolerability/response. Primary efficacy assessment was responder rate during open-­‐label period (response defined as ≥50% seizure frequency reduction from baseline of initial trial). Secondary assessments included seizure freedom rate and reduction in 28-­‐day seizure frequency (from baseline of original trial) during open-­‐label period. Results: In total, 144 patients entered the extension study, of whom 72 had received placebo and 72 had received zonisamide during the initial trial; 99/144 (68.8%) patients completed the study. During open-­‐label period, 81/144 (56.3%) patients were responders (95% confidence interval [CI], 47.7%, 64.5%). Results were similar for patients who initially received placebo (40/72; 55.6%; 95% CI, 43.4%, 67.3%) and zonisamide (41/72; 56.9%; 95% CI, 44.7%, 68.6%). Overall, 16/144 (11.1%) patients achieved seizure freedom during open-­‐label period (95% CI, 6.5%, 17.4%); results being identical for patients initially receiving placebo and zonisamide (for both populations: 8/72; 11.1%; 95% CI, 4.9%, 20.7%). Seizure frequency reduction was maintained throughout the study; the median percentage decrease in seizure frequency being 65.9% during open-­‐label period. Conclusions: The efficacy of adjunctive zonisamide in paediatric patients with partial epilepsy was maintained over a treatment period of >1 year. PP7.6 -­‐ 687 Does vigabatrin treatment for infantile spasms cause visual field defects? An international multicenter study Riikonen R, Carmant L, Dorofeeva M, Hollody K, Krajnc B, Rener Primec Z, Szabo I, Wohlrab G, Sorri I. Kuopio, Finland -­‐ [email protected] There exists little information how often the vigabatrin (VGB) treatment for infantile spasms (IS) causes irreversible visual field defects (VFDs). The aim of this study was to examine IS patients at school age for visual fields to see whether the VGB treatment in infancy had caused defects. Patients and Methods This study included 34 children aged 11 (range 8 to 22 years). Six centers were involved in the study. Nine children had tuberous sclerosis (TS), two other symptomatic (mild brain malformations) and the remaining 23 cryptogenic aetiology for their spasms. Visual fields were examined by the Goldmann kinetic perimetry, by the static Humphrey or Octopus perimetry by experienced perimetrist. Visual fields were re-­‐evaluated by the ophthalmologist (I.S). Results We found typical VGB-­‐attributed visual field defects altogether in 12/34 (35%) patients. The defects were mild in 5, moderate in 4 and severe in 3 cases. One child out of 12 children who used VGB less than one year (Group 1) had a mild VFD. Four of 9 patients (44%) using VGB up to 22-­‐24 months and 7/13 patients (53%) using VGB more than 2 years (Group 3) had VFDs. Defects were mild (2), moderate (1) and severe (1) in the Group 2, and mild (2), moderate (3) and severe (2) in the Group 3. The mean cumulative doses were 155 g (Group 1), 808 g (Group 2) and 2547 g (Group 3), respectively. The patients with TS had more VFDs (6/9 patients) but their VGB treatment was also longer. The frequency of VFDs varied in different centers. Conclusions The VFDs were found in the same frequency as reported in adults. The plasticity of an infant retina seems not to prevent from the damage. The risk/benefit ratio should always be carefully considered when using VGB. Treatment should be as short as possible. PP7.7 -­‐1583 The effectiveness of a low-­‐dose oral diazepam treatment to prevent recurrence of febrile seizures Park HJ, Kim SY, Choi SH. MBL Children's Hospital, Eulji Medical University, Korea -­‐ [email protected] Purpose: Diazepam suppositories or oral diazepam have been used to prevent recurrence of febrile seizures(FS). But this strategy cause many side effects such as sleepiness, lethargy, irritability, and ataxia. This study aimed to investigate the optimum dose of diazepam to reduce the recurrence of FS and side effects in children who have had a febrile seizure attack. Methods: The subjects of this study included 528 children with FS who were admitted to Eulji University Hospital from 2008 to 2011. The children divided into four groups according to the dose of diazepam: Group I, 121 patients, received no diazepam therapy, Group II, 129 patients, received oral diazepam in a single dose of 0.1mg/Kg after the febrile seizure, Group III, 127 patients, 0.2mg/Kg, and Group IV, 151 patients, 0.3mg/Kg, respectively. Results: Seizures recurred in 6 of 129 children (4.7%) in Group II, 1 of 127 (0.8%) in Group III, and none of 151 children in Group IV. For the 121 untreated patients, FS recurred in 20 children (16.5%). This study revealed a significant difference in the rate of recurrence of FS between children treated with diazepam and those who were not. And the recurrence rate was decreased by the increment of the dosage of diazepam. The adverse effects were observed in 19.9% of children with diazepam, 3.9% in Group II, 12.6% in Group III, and 39.7% in Group IV. The rate of adverse effects was also increased with the increment of dosage. Conclusion: An oral diazepam therapy will reduce the recurrence of FS during the same febrile illnesses. 85 We think the optimum dose of diazepam is 0.1mg/Kg or 0.2mg/Kg rather than 0.3mg/Kg. However, the use of oral diazepam after a FS should be carefully considered with weighing the benefits and potential adverse effects. PP7.8 -­‐1576 Successful desensitization of oxcarbazepine and ethosuximide after cutaneous adverse drug reactions and HLA genotype in Korean Lee BL, Yu H, Lee M, Lee J. Department of Pediatrics, Pusan Paik Hospital, Inje University College of Medicine, Korea -­‐ [email protected] Objective: Allergic reaction to specific antiepileptic drugs (AEDs) can occur in some patients and require a change of therapy. An alternative strategy is to desensitize the patients to the offending drug. This study aimed to investigate the usefulness and safety of desensitization to oxcarbazepine (OXC) and ethosuximide (ETX) in patients who had cutaneous adverse drug reactions. Methods: We enrolled 20 patients who had good initial response to OXC (n=19) or ETX (n=1), but who discontinued due to cutaneous adverse drug reactions. Although alternative AEDs were tried on our patients, their seizures were refractory. Therefore, desensitization to OXC was tried in 18 children with partial seizures and one child with paroxysmal kinesigenic dyskinesia (PKD), and to ETX was attempted in one child with atypical absence seizures. High-­‐resolution human leukocyte antigen (HLA)-­‐
A, and -­‐B genotyping was performed to investigate the association between specific HLA allele and OXC-­‐induced cutaneous adverse drug reactions. Results: The median age at desensitization was 11.3 ¡¾ 3.5 years (range 4.8-­‐
16.2 years) and the mean duration of follow-­‐up was 16.2 ¡¾ 8.7 months (range 5-­‐37 months). Nineteen patients completed the desensitization protocol to a target dosage over 2-­‐5 months. Five children developed mild itching and erythema during desensitization, but the symptoms disappeared after the next dose increment was withheld for a short period. We did not find specific HLA genotypes associated with OXC-­‐induced cutaneous adverse drug reactions. The frequency of seizure or dyskinesia was reduced to less than baseline in 18 patients. At last follow-­‐
up, eight patients were seizure-­‐free, five patients showed > 90% reduction and the other four patients had > 50% reduction. Conclusions: The desensitization protocol was well tolerated and safe without serious allergic reactions. When allergic reactions occur with OXC or ETX and there are no effective drugs, desensitization can be a useful alternative. PP7.9 -­‐2061 Haematological parameters in children with epilepsy treated with levetiracetam monotherapy Dinopoulos A, Paschalidou M, Tsirouda M, Garoufi A, Zafiropoulou F, Attilakos A. 3rd department of Pediatrics, University of Athens, "Attikon" University Hospital, Greece -­‐ [email protected] Objectives: Levetiracetam (LEV), a newer broad spectrum antiepileptic agent, is used successfully as monotherapy for partial onset seizures, rolandic epilepsy and myoclonic epilepsy and appears to be well tolerated with mild adverse effects. However, in contrast with the older antiepileptic drugs which are well known to cause hematological changes, the effect of LEV is not yet sufficiently investigated. The aim of this study was to investigate prospectively the hematological effects of LEV in children with epilepsy. Materials and Methods: The study population consisted of 20 children (8 males, 12 females, aged 2 to 15 years old, mean age 6,5±4,16 years) with epilepsy treated with LEV monotherapy. None of the children were receiving any form of AED medication prior to LEV initiation. Complete blood count (CBC) was performed in all children, before and at 2 and 6 months of LEV monotherapy. Results: Lymphocyte absolute count was significantly decreased at 6 months (p=0,021) of LEV monotherapy. The rest of the white blood cells count as well as the red blood cells parameters and the platelets were not altered. Conclusions: LEV monotherapy may significantly decrease lymphocyte count at six months of treatment in children with epilepsy. This might indicate the need to monitor lymphocyte count and infection tendency in children receiving LEV. The depletion of lymphocytes, which is a primary component of the immune system could be associated with the higher incidence of infections reported in children receiving LEV. Further prospective studies are needed to investigate the effect of LEV in lymphocyte numbers and the possible association with the infection frequency reported in LEV patients. PP8 Learning disorders/ immunology Günter Bernert Learning PP8.0 -­‐1978 Rising prevalence of CVI in main stream education calls for a different approach Depourcq M, Vandamme AL, Bonamie E, Keppens K. De Kade, Spermalie, Bruges, Belgium -­‐ [email protected]­‐spermalie.be 86 Prevalence data indicate that CVI (Cerebral Visual Impairment) now is the leading cause of vision impairment in children. Better ability of the school support teams in dealing with CVI-­‐related problems ensure that more children remain in main stream education. Whereas better general awareness for (presumption of) visual dysfunction leads to more referrals to CVI-­‐clinics. Therefore we notice an increasing population of children with CVI in main stream education over the last five years. The presence of students with CVI nearing or in secondary education calls for a customized, specific, often multidisciplinary approach . Objectives Better support of CVI students in main stream secondary education. Materials and methods Prevalence data of the home intervention team Accent, De Kade, Spermalie Bruges. For better understanding of the needs of CVI students, they are referred to our multidisciplinary team. The data of these investigations are collected in a retrospective study. Results Between 2004 and 2008 only 2 students with CVI attended main stream secondary education and were supported by home intervention team Accent and/or the school support team Spermalie . Between 2009 and 2012 this amount increased to 12 students with CVI. We will give a detailed overview of their needs and concerns and of the typical problems they are confronted with. We will also provide information about the current approach and support. Conclusions Students with CVI in main stream secondary schools demand a different approach and/or support package than children with CVI in primary schools. PP8.1 -­‐1634 G.CVI.Tods, a novel diagnostic tool in the assessment of Cerebral Visual Impairment in the young child K. Van Parijsa MSc, A. Vandeputa OT, G. Peirensa,b MD, E. Ortibusa,b MD, PhD. Centrum Ganspoel, Belgium, bUniversity Hospitals Leuven, Department of Pediatric Neurology, Leuven, Belgium -­‐ [email protected] Objectives: Cerebral Visual Impairment (CVI), a neurological condition characterized by an impaired visual perception, has a large negative impact on global development. Early detection and early intervention leads to an improved quality of life. In children under 3 years and in those with a multiple handicap, diagnosis of CVI is largely based on observational and subjective methods, due to language or motor disabilities. Moreover, normative data for visual field size are lacking. Materials and methods: Ganspoel, an institution for the care for visually impaired people, set out to construct a standardized battery for the assessment of visual perceptual skills in this age group. Flemish children of 18, 24 and 30 months with a normal global development and a normal refraction, performed the G.CVI.Tods. The battery consists of a different constellation of subtests depending on age: • Visual recognition of o 3D situations (all) o 2D situations (line drawings (30m), colored images & photos (all)) o single objects (photos (18m), line drawings (24, 30m), black & white images & photos unconventional viewpoint (30m), colored images (all)) o simple objects (18m) • Motion pursuit (all) • Visual field assessment (all) • Daily visual functioning (18m) Results: Sixty-­‐four children were examined at 18 months, 67 at 24m and 77 at 30m. Sum scores of the visual recognition tasks and of the pursuit of motion task, the highest scores for every quadrant of the visual field and the questionnaire of daily visual functioning were plotted in frequency distributions per age. Split-­‐half reliability, Cronbach alpha and correlations between the different subtests of the visual recognition tasks showed valid and reliable results. Conclusion: Normative data have been gathered for a standardized battery for the assessment of visual perceptual skills in children of 18, 24 and 30 months. In a next project, validity will be evaluated. PP8.2 -­‐1914 Functional MRI-­‐guided probabilistic tractography of cortico-­‐cortical and cortico-­‐subcortical language networks in children Broser P, Groeschel S, Hauser T, Lidzba K, Wilke M. Pediatric Neurology & Developmental Medicine, University of Tübingen, Germany -­‐ [email protected]­‐tuebingen.de In this study, we analyzed the structural connectivity of cortico-­‐cortical and cortico-­‐ subcortical language networks in healthy children, using probabilistic tractography based on high angular resolution diffusion imaging. In addition to anatomically defining seed and target regions for tractography, we used fMRI to target inferior frontal and superior temporal cortical language areas on an individual basis. Further, connectivity between these cortical and subcortical (thalamus, caudate nucleus) language regions was assessed. Overall, data from 15 children (8f) aged 8–17 years (mean age 12.1±3 years) could be included. A slight but non-­‐significant trend towards leftward lateralization was found in the arcuate fasciculus/superior longitudinal fasciculus (AF/SLF) using anatomically defined masks (p>.05, Wilcoxon rank test), while the functionallyguided tractography showed a significant lateralization to the left (pb.01). Connectivity of the thalamus with language regions was strong but not lateralized. Connectivity of the caudate nucleus with inferior-­‐frontal language regions was also symmetrical, while connectivity with superior-­‐temporal language regions was strongly lateralized to the left (pb.01). To conclude, we could show that tracking the arcuate fasciculus/superior longitudinal fasciculus is possible using both anatomically and functionally-­‐defined seed and target regions. With the latter approach, we could confirm 87 the presence of structurally-­‐ lateralized cortico-­‐cortical language networks already in children, and finally, we could demonstrate a strongly asymmetrical connectivity of the caudate nucleus with superior temporal language regions. Further research is necessary in order to assess the usability of such an approach to assess language dominance in children unable to participate in an active fMRI study PP8.3 -­‐1910 Academic achievement of 7 year old children in Wales born to mothers taking anticonvulsants in pregnancy Lacey AS, White CP, Pickrell WO, Rees MI, Thomas RH. Health Informatics Research Unit, Institute of Life Science, Swansea University, Swansea, UK -­‐ [email protected] Objective: Prospective studies suggest that education attainment of children exposed to anticonvulsants in utero is poorer than expected and drug dependent. To avoid accusations of selection bias we used routinely collected education data on a population basis to compare academic achievement of children exposed to anticonvulsants in utero with those who were not. Methods: Using the Secure Anonymised information Linkage (SAIL) database of primary care records in Wales we identified children of women with a diagnosis of epilepsy and recorded the mother’s anticonvulsant prescription history. Using national standardised testing the percentage of children of a mother with epilepsy achieving the expected level or above in English or Welsh (first language), mathematics and science were compared to all those without a mother with epilepsy. Results: 481 children were identified and 291 mothers took no drugs during the pregnancy. 165 children were exposed to a single anticonvulsant and 25 to polytherapy (11 including Valproate). 81 children were exposed to Valproate in utero, 57 to Carbamazepine, 12 to Phenytoin and 15 to Lamotrigine. 68% of children whose mothers were taking any single anticonvulsant achieved the standard compared with 80% of all children (p= 0.0003). For children exposed to Valproate the figure was 65% (p=0.002) and 47% for Lamotrigine (p=0.004). There was no difference for those whose mothers took Carbamazepine (p=0.49) or Phenytoin (p=1.0) in pregnancy. Similar results were found in the individual assessments for language, mathematics and science. Only 52% of children whose mothers took more than one drug in pregnancy achieved the standard (p=0.008). Conclusions: Academic achievement is significantly reduced for children exposed to Valproate, Lamotrigine or combinations of anticonvulsants in utero. This study supports the increasing concern that foetal exposure to certain anticonvulsants is deleterious to later cognitive development. PP8.4 -­‐1626 Long-­‐term neuropsychiatric follow-­‐up in hyperprolinemia type 1 Di Rosa G, Nicotera N, Lenzo P, Spanò M, Tortorella G. Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences. Unit of Infantile Neuropsychiatry, University of Messina, Italy -­‐ [email protected] Objectives: Although a growing number of patients has been reported, the neuropsychiatric phenotype associated to hyperprolinemia type 1 (HPI) is still under debate. We previously described a small sample of patients with HPI. Now we report an expanded sample with HPI, long-­‐term followed-­‐up at our Unit for a mean duration of 11 years. Patients&Methods: Neuropsychiatric features and course of 10 patients (3M), actual age range 9-­‐21yrs (median 15,3 years) diagnosed with HPI were analyzed. Results: Clinical course was characterized by epileptic manifestations and/or cognitive impairment at onset , and, subsequently replaced by prevalent psychiatric disorders such as behavioral disturbances and aggressiveness. Social behavior and relational skills were the most markedly impaired in the majority of cases. Learning disorder was present in one patient. Behavioral and psychiatric symptoms were explored in all patients by Child Behavioral CheckList (CBCL) parents' interview. No relationship arose between CBCL scale scores and plasma proline levels, by Pearson's correlational analysis. All tests were 1-­‐tailed, we used an alpha level of 0.05 to assert statistical significance. Any correlation among the eight syndrome CBCL subscale scores, the plasma proline levels and IQs of the 10 patients was significant. As it could be expected, the patients' IQs were inversely related with the total CBCL scores (r= -­‐0,573; p<0,05). Conclusions: HPI appeared to be a neurodevelopmental disorder with a complex clinical course. In our sample psychiatric and behavioral features were the most prevalent at the long term follow-­‐up. Two unusual findings arose from this series: two patients with West syndrome and one with a complex learning disorder. Further series of HPI patients will help to define the neuropsychiatric phenotype of this disorder, meanwhile, HPI may be included in the diagnostic assessment of neurological and psychiatric patients. PP8.5 -­‐2096 Genetic intellectual disability; the Romanian experience based on clinical, cytogenetic and array-­‐CGH techniques Barca D, Arghir A, Tutulan-­‐Cunita AC, Papuc SM, Iliescu C, Burloiu C, Tarta-­‐Arsene O, Minciu I, Motoescu C, Craiu D, Budisteanu B, Budisteanu M. Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Psychiatry Hospital, Bucharest, Roemania -­‐ [email protected] 88 Objective: Global developmental delay (GDD) in younger children and intellectual disability (ID) are common reasons for referral in pediatric neurology, mental retardation(MR) affecting 2-­‐3% of the general population and being the most common developmental disability. The advances of genetic testing increased the diagnostic yield of unexplained GDD/ID and subsequently the recognition of certain syndromes. The aim of this paper is to present the experience of our team in the investigation of children with GDD/MR using classical and molecular genetic techniques. Material and methods: A large number of children -­‐ 450 aged beetwen 3 months and 17 years were included in a study regarding the identification of genetic causes of intellectual disabilities. Personal and familial history, clinical (including neurological, dysmorphological, psychological) and paraclinical examinations (brain imaging, EEG, ultrasounds, X-­‐rays) were performed for all the children. Children with MR, autistic spectrum disorder, dysmorphic features and/or malformations were selected for genetic testing, GTG-­‐
banded karyotype, FISH, arrayCGH being performed. Results: A specific cause for ID was identified in 72 children (16%): a chromosomal abnormality was identified in 54 cases (12%), microdeletion syndromes in 52 children (11,5%), recognizable syndromes in 50 cases (11%). Array-­‐CGH was perfomed in 45 patients with normal karyotype, but severe phenotype and 8 cases with cytogenetic abnormalities. Rare disorders were identified: 3p interstitial deletion (1 case), 4p interstitial deletion (1), 12p duplication (1), 15q deletion (1), 8p deletion (1 case), 18q deletion (1 case), unbalanced translocations, 4 cases -­‐ between 3q and 20q (1 case), 4p and 10q (2 siblings), 4p and 8p (1 case) and MECP2 duplication syndrome (1), Xp duplication (1). Conclusions: While clinical diagnosis and conventional techniques form the mainstay of investigation of children with ID, array CGH proved important diagnostic tool. Immuno PP8.6 -­‐2051 Optic neuritis-­‐ etiology and results of treatment Dunin-­‐Wisowicz D, Tomaszek K, Borkowska J, Kanigowska K, Hautz W, Jówiak S. Neurology and Epileptology Department, Warsaw, Poland -­‐ [email protected] Objectives: Optic neuritis is one of the very severe ophthalmological and neurological problems. Primary cause of optic neuritis is often unknown. The proper early diagnosis and introduction of treatment is important. Optic neuritis cases in children and teenagers are presented. Material and Methods: Five patients (4 boys, 1 girl) at the age of 9 to 13 years with bilateral optic neuritis were treated and followed-­‐up. The magnetic resonance imaging, as well as cerebrospinal fluid (CSF) analysis and different bacteriological, virusological, parasitological, metabolic and genetic test were performed. Results: Pathological changes were present in ophthalmological examinations and also in MR scans and CSF analysis. In one case optic neuritis was associated with meningoencephalitis. Etiological factor of the optic nerves inflammation involvement was confirmed only in one patient. In this case, infection with human cytomegalovirus (HCMV) based on polymerase chain reaction method (PCR) was diagnosed. Lyme disease, tuberculosis, syphilis, herpes zoster, toxoplasmosis, toxocarosis, lupus, vasculitis and diabetes were excluded during diagnostic process. All but one patient recovered completely after treatment with methylprednisolone and intravenous immunoglobulins. Patient with HCMV infection was successfully treated with intravenous ganciclovir (GCV). One male adolescent suffered from severe, progressive optic neuritis and neuropathy. In this patient Leber’s hereditary optic neuropathy was not confirmed. There were no multiple sclerosis cases. Conclusions: Difficulties with establishing the cause of the optic nerve inflammation involvement are presented frequently. Genetic tests should also be performed. Antiviral treatment seems to be important in some optic neuritis cases. PP8.7 -­‐2132 Acute necrotizing Encephalopathy (ANE) caused by mutation in RANBP2: three episodes in two affected family members Amsallem D, Pâris C, Mougey C, Bévalot J, Rodriguez D, Burglen L. Department of Paediatric Neurology, University Hospital Jean Minjoz, Besançon, France -­‐ [email protected]­‐besancon.fr We report a new family in which two children are affected with an autosomal dominant, incompletely penetrant, ANE. A previously healthy 5-­‐year-­‐old French girl presented in 02/2002, with dysarthria, unsteady gait, impaired consciousness, 3 days after fever, cough, vomiting. Laboratory tests were unrevealing, excluding meningitis, encephalitis, inborn errors of metabolism and toxin exposure. Brain T2-­‐weighted MRI showed bilateral signal intensity in thalamus, brainstem, external capsule and cerebellum. With high-­‐dose steroids, she recovered with mild gait disturbance and slowness. MRI brain 10 months later showed only residual lesions in brainstem and cerebellum. Recurrence occurred seven years later. Clinical and radiological signs were more severe. Deterioration led to quadriplegia. CSF protein level was 111 mg/dL. Methylprednisolone pulse therapy had not 89 the same good impact. Leigh syndrome was ruled out before diagnosis of ANE was confirmed. The patient and her mother are heterozygous for a missense mutation (c.1880C-­‐-­‐>T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2).The outcome was poor : coma for 14 days, more one year in rehabilitation center and she recovered from hypotonia, gait abnormality, tremor, poor swallowing and speech impairment. Four years after hospitalization, she has no cognitive impairment, learns about horticulture, can walk. Mood disorder still remains. A 7-­‐year-­‐old boy presented this year with coma and vomiting, three days after the onset of a febrile illness. His parents were awareness because the girl and he were second cousins. MRI imaging showed multifocal symmetric lesions involving the thalamus, brainstem, external capsule, claustrum and medial temporal lobes. He has the same missense mutation. He was treated with early and repeated high-­‐dose steroids, gammaglobulin, plasmapheresis. Its outcome is better and faster but other case studies are required. The mothers of the two children are carriers of the RANBP2 mutation and had never had any neurologic pathology. PP8.8 -­‐2095 Anti-­‐NMDAr encephalitis; presentation of 3 pediatric cases with full recovery Mastroyianni S, Voudris K, Mavrikou M, Triantafyllidou A, Maggina P, Katsarou E. Department of Neurology, “P and A Kyriakou” Children’s Hospital of Athens, Greece -­‐ [email protected] Anti-­‐N-­‐methyl-­‐D-­‐Aspartate receptor (anti-­‐NMDAr) encephalitis is an autoimmune and often paraneoplastic, neuropsychiatric syndrome affecting children and young adults. Currently, the diagnosis is straightforward with the detection of auto-­‐antibodies against NMDA-­‐receptor in serum and/or CSF and outcome is usually favorable with prompt treatment. However recovery period is long, sometimes with relapses, and therefore uncertainties regarding the type and length of immunotherapy remain. We report 3 cases of anti-­‐NMDAr encephalitis presented over the period Februrary 2010 to April 2011. The patients were girls aged at presentation; patient-­‐1: 11y, patient-­‐ 2: 6y, patient-­‐3: 10y. All had developed after a viral-­‐like illness, a deteriorating condition which progressed from psychiatric symptoms with seizures and dyskinesias into a state of unresponsiveness, with catatonic features and autonomic instability. Patients -­‐1 and -­‐2 presented as “acute psychosis” with prominent dyskinetic features and normal brain MRI, EEG and CSF findings. Patient-­‐3 was presented as “limbic encephalitis” (CSF pleocytosis, seizures responding to conventional antiepileptics and abnormal brain MRI). The diagnosis of anti-­‐NMDAr encephalitis was confirmed in our three cases, 4wks, 7wks and 1wk after the symptom presentation. None of the patients had associated tumor. All patients received 1st line immunotherapy with IVIg and pulse methylprednisolone followed by oral steroids with slow tapering (8mo, 3mo and 2mo respectively). Cyclophosphamide was added to the treatment of patients -­‐1 and -­‐3, after 2 weeks, because of the severity of neuropsychiatric symptoms (5 and 4 monthly cycles respectively). Patient -­‐2 had improved considerably before the onset of treatment and after 2 months of 1st line immunotherapy she had minimal behavioral deficits. Treatment discontinued after substantial clinical and cognitive improvement (total treatment duration 9mo, 3mo and 5mo respectively). We present the clinical data of 3 children with anti-­‐NMDAr encephalitis who started immunotherapy at different stage of the disease. All children have eventually returned to school without problems. PP8.9 -­‐1902 Tick-­‐Borne Encephalitis in Children -­‐ High Risk of Incomplete Recovery Fowler Å, Forsman L, Eriksson M, Wickström R. Neuropediatric Unit, Dept of Women´s and Children´s Health, Karolinska Institutet, Sweden -­‐ [email protected] Tick-­‐borne encephalitis (TBE) is a vector-­‐borne disease that affects both adults and children. In adults, TBE is followed by an incomplete recovery in up to 40%; the main complaints being headache, fatigue and cognitive impairment. The situation for children with TBE is less well studied and cognitive problems following TBE may be overlooked. Objective: To examine long-­‐term outcome after tick-­‐borne encephalitis (TBE) in children. Materials and Methods: In this population-­‐based cohort, 55 children with TBE with CNS involvement infected during 2004-­‐
2008 were evaluated 2-­‐7 years later using the Rivermead post-­‐concussion symptoms questionnaire (n=42) and the Behavior Rating Inventory of Executive Functioning (BRIEF) for parents and teachers (n=32, n=22, respectively). General cognitive ability was investigated in a subgroup (n=20) using the Wechsler Intelligence Scales for Children, 4th edition (WISC-­‐IV). Results: At long-­‐term follow-­‐up, 2/3 of the children experienced residual problems, the main complaints being cognitive problems, headache, fatigue and irritability. More than one-­‐third of the children were reported by parents or teachers to have problems with executive functioning on the BRIEF, mainly in areas involving initiating, organizing activities and working memory. Children who underwent WISC-­‐IV testing had a significantly lower working memory index compared with reference norms. Conclusion: A large proportion of children experience an incomplete recovery following TBE with central nervous 90 system involvement. Cognitive problems in areas of executive function and working memory are the most prevalent. Even if mortality and severe sequelae are low in children following TBE, all children should be followed after TBE to detect cognitive deficits. 91 3. POSTERS Cerebral palsy P1 -­‐ 2109 Assessment of bone mineral density disorders in children with cerebral palsy and epilepsy Tosun A, Erisen S, Unuvar T, Dursun S. Adnan Menderes Medical School, Department of Pediatric Neurology, Aydin, Turkey -­‐ [email protected] Objectives: The aim of this study was to evaluate bone metabolism and mineral density disorders; to determine the effect of possible risk factors including immobilization, mental retardation, calcium and vitamin D deficiency, usage of antiepileptic drugs in children with cerebral palsy-­‐ epilepsy. Material and methods: Prepubertal 30 patients with diagnosis of cerebral palsy, 54 with epilepsy and 38 with cerebral palsy-­‐epilepsy and 30 healthy children were included into the study. Serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), 25 OHD3, parathormone(PTH) levels were evaluated and bone mineral density (BMD) were assessed by DEXA. Presence of malnutrition was assessed with Gomez scores. Results: Severe malnutrition was detected in 11% of patients with epilepsy, 36.7% of cerebral palsy, and 44.7% of cerebral palsy-­‐epilepsy. Higher Gross Motor Function Classification System (GMFCS) levels were associated with higher malnutrition rates (p<0,05). Serum Ca levels in cerebral palsy and epilepsy-­‐cerebral palsy groups were detected significantly lower than epilepsy and healthy children groups (p=0,001). The lowest serum 25 OHD3 value was detected in epilepsy-­‐cerebral palsy group (%63,2). Moreover, it was significantly lower in patients receiving more than one anticonvulsant (p < 0.05). Serum 25 OHD3 value was significantly related to sunlight, serum Ca, and level of GMFCS (p < 0.05). However, there was no relation between serum Ca and BMD and seasons. Abnormal BMD was found in 61 patients (50%). Osteoporosis was detected in 3.7% of patients with epilepsy, 50% of cerebral palsy, and 39.5% of cerebral palsy-­‐ epilepsy. Immobility, mental retardation, using of long duration antiepileptic drug were the main reasons for abnormal BMD. Conclusion: Cerebral palsy patients who have immobility, mental retardation, nutrition disorders and receiving antiepileptic drug have higher risk for lower BMD. Serum 25 OHD3 levels should be evaluated in such patients and they should be assessed for BMD periodically. P2 -­‐ 1976 Clinical-­‐imaging correlations in cerebral palsy Minciu I, Barca D, Iliescu C, Tarta-­‐Arsene O, Craiu D. Carol Davila” University of Medicine, Department of Neurology, Pediatric Neurology, Neurosurgery, Psychiatry -­‐ Pediatric Neurology Clinic No.II, Bucharest, Romania Introduction: Neuroimaging is important for identifying cerebral palsy (CP) etiology. Material and method: Using the CP registry, the imaging investigations correlated with clinical data of patients with diagnosis -­‐ CP admitted in Paediatric Neurology Clinic Bucharest during year 2010 were retrospectively analysed. SPCE CP classification (spastic, ataxic, dyskinetic) was used. The motor impairment severity was assessed with GMFCS. All patients underwent cerebral CT or MRI. Lesions were classified as: malformations, periventricular white matter lesions (PWML), grey matter lesions (GML), white and grey matter lesions (WGML), other, no lesion. Statistical software package and chi square test were used for data processing. Results: 379 CP children were analysed. Spastic CP forms prevailed (76.2 %). Most children (>87%) with CP had neuroimaging abnormalities. WML were the most frequent (38,5%), followed by WGML (~30%). PWML were correlated with spastic diparesis (p<0,001). WGML correlated with spastic hemiparesis, and GML with dyskinetic forms (p<0,001). Malformations were significantly associated with ataxic forms and spastic hemiparesis (p<0,001). We found significant correlations between WGML and the presence of epilepsy (p0.001), severe/ profound mental retardation. Microcephaly was correlated with malformations, WGML and "other types of lesions" (p<0.001). Strabismus was present in 92% of the children with PWML (p<0,001). WML were correlated with GMFCS III, IV (p0,000) in our series. WGML were correlated with GMFCS I, but also V (p0.000). Conclusions: Clinical forms and comorbidities were significantly correlated with the type of imaging lesion. The lesion type was correlated with the severity of functional impairment and, most likely, the degree and extent of the lesion, which could not be measured. Therefore, the same type of lesion in terms of description resulted in slight or severe impairment. The CP registry will serve as a base for further research. P3 -­‐ 1961 Development of a clinical algorithm for children with Toe-­‐Walking Wacks M, Sen S, Varghese K, Watson D, Mankad K, O'Driscsoll M, Kinali M. Paediatric Neurology Chelsea and Westminster Hospital NHS Foundation Trust, United Kingdom -­‐ [email protected] 92 Background Toe-­‐walking is a common presentation within Paediatric Neurology and Neurodevelopmental services. Children under 2 years may toe-­‐walk until an independent gait has been established. Although beyond this age, idiopathic toe-­‐ walking occurs, it is a diagnosis of exclusion and warrants assessment to exclude conditions such as cerebral palsy, autism, and neuromuscular diseases. Objectives: 1. Establish the epidemiology of toe-­‐walkers within a large single centre paediatric cohort. 2. Establish an association between toe-­‐walking and other diagnoses. 3. Establish the diagnostic yield of MRI brain and spine in toe-­‐walkers in those with and without additional neurological signs/symptoms. 4. Develop an appropriate clinical algorithm for screening of children presenting with toe-­‐walking. Method We plan to identify children who toe-­‐walk who were seen within Neurology and Neurodevelopmental services in Chelsea and Westminster Hospital from 2009 – April 2013. A retrospective pilot study was carried out of 60 randomly selected children who attended the Neurodevelopmental Services between 2009 and 2013 using the search criteria ‘Toe Walking’; reviewing their clinic letters, assessment reports and investigations. Results of Pilot Out of 60 case notes reviewed, 12 children had definite histories of toe-­‐walking. Of these, 4 had cerebral palsy, 3 had global developmental delay, 2 had autism, 1 had a specific speech and language disorder, 1 had no underlying diagnosis and 1 only had a single audiology review. Four of the 12, had an MRI brain and spine; 3 had normal imaging and 1 had subtle cerebral changes which were thought to unrelated to the toe-­‐ walking. Conclusion The pilot study demonstrated that 12 children (20%) toe-­‐walked. These 12 children showed a significant association with cerebral palsy, autism, speech and language development and global developmental delay. A retrospective study of a larger cohort is currently in progress to produce data allowing the above aims to be met. P4 -­‐ 1946 Quadriplegia following minor trauma in a three year old child with Chiari-­‐I malformation -­‐ a management challenge Nabialek T, Kaliaperumal C, Leonard J, Flanagan M. Temple Street Children's University Hospital, Dublin, Ireland -­‐ [email protected] Introduction: Spinal cord injuries following minor trauma are rare. Ten cases have been described in children. Four were diagnosed with underlying Chiari-­‐I malformation, among whom one had an associated non-­‐displaced atlas fracture. Among patients with Chiari-­‐I malformation one underwent surgery and three were managed conservatively. Case Description: We describe a case of a three and a half year old girl with previously undiagnosed Chiari-­‐I malformation who acquired high cervical spinal cord syndrome (C4 level) with quadriplegia, paradoxical breathing, areflexia, loss of sensation, and urinary retention following tumbling on a sofa. Initial MRI revealed extensive hydro-­‐syringomyelia and Chiari-­‐I malformation. She underwent foramen magnum decompression. Spinal cord oedema and syringomelia improved within 20 days. A ventriculo-­‐peritoneal shunt was inserted for subsequent hydrocephalus. Two months post injury, she remains clinically unchanged. She required mechanical ventilation and is on weaning regime of BiPAP following RSV infection. Discussion: Among victims of minor trauma resulting in spinal injury, the symptoms and their sequence can be similar in children with and without underlying Chiari-­‐I malformation. Malformation was present in 45% of known cases; therefore it should be seen as a risk factor. Possibly Chiari-­‐I malformations remained undiagnosed in some of the patients in the era pre-­‐MRI imaging. In the case described above, there was a management dilemma, when Chiari-­‐I malformation and cord oedema were diagnosed. Considered underlying tumour was ruled out with a follow-­‐up MRI. Conclusion: Asymptomatic Chiari-­‐I malformation can present in children after minor trauma and this can be debilitating. When a well child is diagnosed with Chiari-­‐I malformation this risk should be discussed with parents. Surgery may be needed in asymptomatic patients with Chiari-­‐I and syringomyelia. We recommend a foramen magnum decompression in case of significant neurological compromise following minor trauma. P5 -­‐ 1927 Strength in antagonist muscles of the lower limbs in ambulatory children with bilateral spastic cerebral palsy, 7-­‐16 years, versus typically developing controls Darras N, Tziomaki M, Pasparakis D and Papavasiliou A. Elepap gait analysis and motion analysis center, Greece -­‐ [email protected] Objective: We aimed to compare the pattern of strength development of antagonist muscle groups, between ambulatory patients with Bilateral Spastic Cerebral Palsy (BSCP) and Typically Developing Controls (TDC). Methods: Eighty-­‐six TDC and 142 ambulatory patients with BSCP were grouped in five age groups from age 7-­‐16 in two-­‐year intervals. The strength of hip adductors and abductors, hip extensors and flexors, knee extensors and flexors and ankle dorsiflexors were measured by the same examiner through a Hoggan Microfet2 digital hand held dynamometer. Force data analysis was performed: A) using Absolute Force (AF) in lbs and Β) Normalized 93 Force (NF) to body weight. Descriptive statistical analysis and ANOVAs were used (level of significance= 0.05). Results: Force development graphs of the pairs of antagonist muscles measured showed an almost parallel force development in most of the NF diagrams in both BSCP and TDC. Imbalance in the NF values between the hip extensors and flexors was clearly identifiable in patients; this was related to the fact that hip extensors in ambulatory children with BSCP were exhibiting values close to TDC, while hip flexors were exhibiting significantly lower values across all age groups. The same pattern of imbalance was also found in the other antagonist muscle groups. NF values amplified the imbalance differences as compared to the AF. Conclusion: This study revealed that muscle strength imbalance in ambulatory patients with BSCP is present from at least age 7 years and does not change significantly up to age of 16 years. In BSCP, a constant pattern of significant muscle strength imbalance between antagonist muscles across all ages was identified. Hip abductors, hip flexors and knee flexors were found significantly weaker than adductors and extensors. P6 -­‐ 1887 Variation in health care for children and young people with cerebral palsies: a retrospective multi-­‐centre audit Horridge KA, Balu R, Tennant PWG, Rankin JM. City Hospitals Sunderland, UK -­‐ [email protected] Objectives: To establish whether there is variation in health care for children and young people with cerebral palsies across northern England. Materials and Methods: Retrospective medical record audit of 389 children and young people registered on the North of England Collaborative Cerebral Palsy Survey (NECCPS) living in 15 geographical districts, born 1995-­‐2002, with subsequent data validation by clinicians. Data was collected on cranial magnetic resonance imaging [MRI] (marker of aetiological assessment), hip and spine status, pain and its management, feeding and nutritional status. Results: The audit sample was representative of all contemporaneous cases reported to the NECCPS. There was significant variation between reporting districts in access to MRI, orthopaedic surgeons for the least mobile children and young people, recording of state of spine and of weight and height percentiles (p<0.001). 67% had a discussion about pain recorded, of which 87% had a management plan. Those from the most deprived population quintile were significantly less likely to have had a discussion about pain recorded in their notes than those in the least deprived quintile (p=0.045). Conclusion: There is variation in important aspects of health care, between districts in the north of England. This data will assist with working towards more equitable health care and thus provide more equal opportunities for the best health outcomes for all. P7 -­‐ 1841 Longterm Development of VLBW-­‐Infants with Cerebral Palsy. Results of a population-­‐based study Veelken N, Just K. Asklepios Clinic North, Hamburg, Germany -­‐ [email protected] P8-­‐ 1769 During a 3 years period 91% of preterm infants with birthweight under 1501 g who were born in Hamburg, Germany, were involved in a longitudinal study. Cross-­‐ sectional examinations were performed at the age of 2, 6 and 9 years of age. In 42 of the 371 children (11,3%) cerebral palsy (CP) was definitely found at the age of 6 years. CP was classified as spastic diplegia in 29 (69%) children. In 3 (7%) spastic hemiplegia, in 5 (12%) spastic tetraplegia and in 5 (12%) other forms of CP were found according to the definition of Hagberg. 22 (52%) of these patients were examined again in adulthood at the age of 21-­‐24 years. They were representative in terms of severity of handicap and type of CP. At that age 15 patients suffered from spastic diplegia, 3 from spastic hemiplegia and 4 from spastic tetraplegia. All hemiplegic patients as well as four diplegic patients were able to walk independently. All tetraplegic patients cold not move around anyhow. 4 patients showed a motor disability level I according to GMFCS-­‐classification, 3 patients level II, 6 patients level III and IV and 3 patients level V. 12 patients were living independently or with minor help, 10 patients needed major support or were dependent on continuous help in daily life. Only 6 patients (27%) did not achieve any school graduation, 14 finished with secondary school graduation (7 with "Hauptschulabschluß", 7 with "Realschulabschluß") and 2 with high school graduation (Abitur). 12 patients (55%) showed a Body Mass Index (BMI) below (5 = 23%) or above (7 = 32%) normal range. A major percentage of former VLBW-­‐patients with cerebral palsy is able to achieve normal school education and to live independently despite of a definite motor disability. Only a minor percentage remains dependent on major support. Treatment methods of mild spastic CP from 8 to 15 years of age: a population based study Rackauskaite G, Bech BH, Uldall P, Østergaard JR. Dep. of Pediatrics, Aarhus University Hospital, Denmark -­‐ [email protected] Objectives. To describe the use of splints, physiotherapy, occupational therapy and intramuscular Botulinum toxin injections (BTA) in preteens (8-­‐12y) and teens (13-­‐15y) with mild cerebral palsy (CP). Materials and 94 Methods. A national wide parent questionnaire to 8-­‐15 years old children with cerebral palsy was sent by mail in 2012. A total of 216 participants had mild spastic CP (Gross Motor Function Classification System (GMFCS) level I and II). Proportions of children getting physiotherapy (during the last 12 months), occupational therapy (during the last 12 months), Botulinum toxin injections (during the last 12 months) and use of splints (during the last 3 months) were calculated with a 95 % confidence interval (CI). Odds ratio (OR) for teens compared to preteens were calculated. Results. More preteens used physiotherapy: 82% (CI 76-­‐89%) compared to teens 72% (CI 62-­‐
81%). No difference was found for use of occupational therapy: 38% (CI 30-­‐47%) of preteens and 34% (CI 24-­‐
44%) of teens. A large difference was found for BTA: 17% (CI 10-­‐23%) of preteens and 7% (CI 2-­‐13%) of teens. We only found a small difference in the use of splints, 29% (CI 20-­‐36%) of preteens and 22% (CI 13-­‐ 31%) of teens. The OR differed statistically significantly for BTA (p=0.043), but not significantly for other treatment modalities. Conclusions. We demonstrated a tendency of getting less physiotherapy and occupational therapy, minor use of splints, and a significantly less administration of Botulinum Toxin in teens as compared to preteens in a population based sample of mild CP. Minor use of Botulinum toxin injections can be explained by diminishing dynamic spasticity in older children. The differences in other treatment modalities could not be explained by that, neither by differences in GMFCS levels. Longitudinal studies are needed in order to examine the tendency of declining use of physiotherapy. P9 -­‐ 1573 Long term response following the treatment of hip adductor spasticity in children with cerebral palsy using intra-­‐muscular botulinum toxin a – a single centre experience from Singapore Hian-­‐Tat Ong, Jeremy BY Lin, Karen JL Lim, James HP Hui. Khoo Teck Puat-­‐University Children’s Medical Institute, National University Health System, Singapore -­‐ [email protected] Objectives: To assess the magnitude of the effects of intra-­‐muscular injection of botulinum toxin A (BTX-­‐A) on hip adductor muscles in children with cerebral palsy, and the need for subsequent repeat injections. Methods: Children below 8 years with dynamic spasticity of the hip adductor muscles were prospectively evaluated in a 6-­‐
year period from year 2000 to 2005. Range of motion of the hip was assessed using the Modified Tardieu Scale and recorded as R1 and R2. Muscle tone was assessed using the Modified Ashworth Scale (MAS). Repeat evaluations were performed at intervals of between 4 to 6 weeks, and 3 months post-­‐ injection. Physical therapy was intensified in the 3 months following the injection. The children had subsequent half yearly reviews till December 2012 to assess the need for repeat injections. Results: There were 14 children (11 boys, 3 girls) with a total of 43 hip adductor muscle injections administered in the study period. Five of these children subsequently had repeat injections for the same adductor muscles. Twelve data sets were excluded due to default visits or patient uncooperativeness, leaving a total of 31 data sets analysed. After 4 to 6 weeks, there was an average improvement of 6.7º in R1 and 7.1º for R2. For muscle tone, there was an average improvement of 0.5 on the MAS. Three months post-­‐ injection, there was an average improvement of 5.3º in R1 and 6.5º for R2. Average improvement for muscle tone was 0.4. Conclusion: The beneficial effects of intra-­‐muscular BTX-­‐A injection are evident and maximal by 4 to 6 weeks and for most patients, these benefits continued 3 months post-­‐ injection. This provided an important therapeutic window for intensive physical therapy to take place so as to achieve permanent functional gains, as less than half the patients required re-­‐injection to the same muscles. P10 -­‐ 2161 The biomechanical evaluation of gait in monitoring of treatment in children with cerebral palsy-­‐ preliminary data Kopyta I, Jochymczyk-­‐WoŸniak K, Michnik R, Jurkojae J, Chuchnowska I. Department of Neuropediatrics, Medical University of Silesia, Katowice, Poland -­‐ [email protected] Introduction: Recently the fast progress in the development of systems attending the three-­‐dimensional gait evaluation is being observed. The methods enable the objective gait evaluation of the gait in children with cerebral palsy (CP). One of the indexes used to the analysis is Gillette Gait Index (GGI), complying 16 clinically meaningful kinematic and three-­‐dimensional parameters. Material and method: The study was conducted with application of the three-­‐ dimensional system of gait analysis BTS Smart and carried by the team of pediatric neurologists, physiotherapists and engineers. Spatial-­‐time parameters of gait and courses of angles of joint of lower limbs were determined on the basis of conducted research. Those parameters were used in estimation of Gillette Gait Index. The analyzed group consisted of five CP patients treated with botulin toxin (three children with hemiparesis, one with diparesis and one with quadriparesis), intensively rehabilitated after the botulin treatment. The data were compared to two patients put on rehabilitation without the botulin treatment. The patients treated with botulin were evaluated three times: before the botulin administration, then three and six months after it. In the other patients’ group the evaluation was conducted three months after rehabilitation 95 start. The results of gait evaluation were compared to the gait pattern of the healthy children; the normal values were worked out by the authors. Results After the botulin treatment and rehabilitation the increase of the gait speed and frequency of steps were observed; the GGI decreased both after three and six months of observation. Conclusion: The authors regard the results presented above as the pilot-­‐study; the evaluation of the larger groups of children with cerebral palsy is conducted. In the authors ‘opinion the objective method of CP children gait evaluation may be the helpful tool for clinicians to optimize the way of CP children treatment. P11 -­‐ 1780 Dystonic cerebral palsy in monozygotic twins with 10p15.3 microdeletion syndrome Vargiami E, Ververi A, Kyriazi M, Papathanasiou E, Gioula G, Gerou S, Al-­‐Mutawa H, Kambouris M, Zafeiriou DI. 1st Department of Pediatrics, Aristotle University of Thessaloniki, Greece -­‐ [email protected] Submicroscopic deletion of 10p15.3 is a rare genetic disorder, currently reported in 21 unrelated patients. It is mainly associated with cognitive/developmental deviations, speech delay/language disorder, motor delay, craniofacial dysmorphism, hypotonia, brain anomalies and seizures. The size of the deleted region ranges between 0.15 and 4 Mb and does not generally correlate with patients¢ phenotype. A monozygotic female twin pair with a de novo 2.7 Mb deletion of 10p15.3 is herein reported. The girls presented at the age of 8 months with severe developmental delay and failure to thrive since the first month of life. Their perinatal and family history was unremarkable. On admission they both exhibited generalized dystonia with increased muscle tone and excessive deep tendon reflexes, microcephaly, progressive swallowing dysfunction, laryngomalacia, small omphalocele, mild dysmorphic features and complete absence of head control, voluntary movements and visual/auditory responsiveness. Both patients¢ brain MRIs demonstrated dilatation of ventricles, subarachnoid spaces, anterior interhemispheric fissure and sylvian fissures bilaterally. Cranial radiography revealed partial fusion of both coronal sutures. Visual and brainstem auditory evoked potentials were markedly abnormal, indicating severe visual and sensorineural hearing impairment. The electroencephalogram, as well as a screening for inborn errors of metabolism, were unremarkable. Both patients required gastrostomy and tracheostomy before the age of 1 year. They were, additionally, managed with physical therapy, as well as baclofen and low-­‐
dose haloperidol. Their current state at the age of 2 years is relatively stable. The index patients¢ phenotype includes features, such as dystonic cerebral palsy, visual and sensorineural hearing impairment, laryngomalacia, craniosynostosis and omphalocele, which have not been previously reported in individuals with 10p15.3 deletion. It is necessary to consider these novel clinical features and investigate their possible relationship with the recently recognized 10p15.3 microdeletion syndrome. P12 -­‐ 2084 Foramen Magnum Decompression as Emergency Surgery for Acute Upper Cervical Spinal Cord Compression in a 3 years old girl with Tetraplegia Aziz M, Kaliaperumal C, Sattar M. Children University Hospital, Temple Street, Ireland -­‐ [email protected] Background: Spinal cord injuries (SCI) are relatively uncommon in paediatric age group. Incidence varies from 1 to 10% of all spinal injuries. In United States, about 12000 people a year sustain a spinal cord injury. Main causes in paediatric age group are birth injuries, falls, motor vehicle accidents, sports injuries, diving and trampoline accidents and violence (gun shots or stab wounds). Chiari malformation as a cause of acute SCI is rare, and has been reported in four cases previously. Case description: A 3 years old girl previously healthy child presented with acute tetraplegia after a minor fall. She was playing on top of a sofa and landed on the cushion seats. Sudden loss of bilateral upper limb power was noted and child was brought to local emergency department and transferred to national paediatric hospital as spinal injury. Results of Investigations Initial assessment showed horizontal movement of both feet but not against gravity, power 2/5 bilaterally. Due to trivial nature of injury, an emergent magnetic radiological imaging (MRI) was not obtained. MRI of cervical spine carried out 8 hours after admission and 18 hours after event showed cerebellar tonsillar herniation by 7 mm and Chiari Malformation Type I with severe oedema of cervical spinal cord. Treatment: She underwent emergency Foramen Magnum decompression. Surgical findings are hypertrophied posterior atlanto-­‐ occipital membrane and hard and tough occipital and posterior foramen magnum skull bones. Post decompression, free cerebrospinal fluid (CSF) flow and cerebellar tonsils pulsations was noted. Post-­‐ operatively, child remained tetraplegic and currently undergoing intensive rehabilitation. Discussion: Trivial nature of trauma should never be underestimated, with development of acute and rapidly deteriorating paralysis. 96 Epilepsy P13 -­‐ 2112 Mutations in PLCB1 in Early Infantile Epileptic Encephalopathy: Expansion of the phenotypic and genotypic disease spectrum McTague A, Wentzensen I, Meyer E, Ngoh A, Applegate C, Batista D, Kossof E, Wang T, Kurian MA. Neurosciences Unit, UCL-­‐Institute of Child Health, London, United Kingdom -­‐ [email protected] Introduction: Phospholipase C beta 1 (PLCB1) is a post-­‐synaptic receptor-­‐activated G protein-­‐coupled phosphodiesterase, which plays a key role in diverse developmental and functional aspects of the central nervous system. Homozygous deletions of chromosome 20p13 disrupting the promoter region and first 3 coding exons of PLCB1 have been described in two reports of early infantile epileptic encephalopathy (EIEE) occurring within consanguineous families 1, 2. We describe a patient presenting with developmental delay and epilepsy with novel PLCB1 mutations. Methods: Case note review and molecular genetic investigations. Results: The patient presented at 6 months of age with developmental regression followed by the onset of intractable focal and generalised seizures from 10 months. EEG revealed generalised slowing and multi-­‐focal discharges. MRI brain showed a hypoplastic corpus callosum and generalised decrease in brain volume. Diagnostic microarray studies revealed a heterozygous 476Kb deletion of 20p13 (encompassing part of PLCB1), which was maternally inherited. The deletion breakpoints were between 8,094,442-­‐8,094,510 bp and 8,580,65-­‐8,580,722 bp. Direct Sanger sequencing revealed a novel intron 1 splice site variant, which was paternally inherited (c.99+1G>A). Conclusion: Mutations in PLCB1 cause a wide spectrum of early onset epileptic encephalopathies, now including non-­‐specific EIEE. The heterozygous deletion identified in this African-­‐American case appears almost identical to that reported by in a family of Palestinian descent2 suggesting a role for the flanking LINE elements in this recurrent deletion. This novel report of compound heterozygosity expands the PLCB1 phenotype and genotype and provides an excellent example of chromosomal microdeletions unravelling deleterious recessive mutations which cause human disease. P14 -­‐ 1538 Severe neonatal epileptic encephalopathy with burst-­‐suppression pattern with mutation in PIGA gene-­‐a case report Maier O, Jaeger G, Joset P, Steindl K, Pajarola S, Rauch A. Children's Hospital of Eastern Switzerland, department of child neurology, Switzerland -­‐ [email protected] We report a male neonate, gestational age of 38 weeks, birth weight 4600 grams delivered by cesearean section and presenting with respiratory distress requiring intubation and mechanical ventilation. On day 5 the child developed tonic seizures with ocular deviation and with a burst-­‐suppression pattern in the EEG. The seizures were refractory to conventional antiepileptic drug therapy (Phenobarbitone, Phenytoin, Levetiracetam, Vigabatrin). Brain MRI showed cerebellar and opercular atrophy and white matter immaturity. The child had dysmorphic features with prominent forehead, depressed nasal bridge, high arched palate. The central tone was poor. On echocardiac evaluation there was mild pulmonary hypertension, but no other pathology. Abdominal ultrasound was normal. In view of uncontrollable seizures and the dismal prognosis associated with the MRI findings, a decision was taken with the parents to limit intensive care measures. The child died on day 15 due to respiratory failure. Genetic analysis (exom sequence analysis, confirmed by Sanger sequence analysis) revealed a mutation (c.532C>T (p.Arg412) in the PIGA gene (phoshatidylinositol glycan class A (MIM 311770), the mother is heterozygote for this mutation. PIGA mutations show x-­‐linked inheritance. The phenotype was described for the first time in 2012 (Johnston et al. 2012). Mutation in the PIGA gene can cause severe epileptic encephalopathy with burst-­‐suppression pattern in EEG and are associated with brain pathology, dysmorphic feature, muscular hypotonia and poor prognosis. The Inheritance is X-­‐linked. P15-­‐ 1733 A novel SCN2A missense mutation in a Slovenian girl with early-­‐onset epileptic encephalopathy Gnidovec Strazisar B, Writzl K, Paro Panjan D, Neubauer D, Nakamura K, Matsumoto N, Saitsu H. Department of Child, Adolescent and Developmental Neurology, University Children’s Hospital, Ljubljana, Slovenia -­‐ [email protected]­‐lj.si Objective: Mutations in SCN2A gene are associated with variety of epileptic syndromes. We report a novel SCN2A missense mutation in a girl with severe early-­‐onset epileptic encephalopathy. Case report: Soon after birth patient presented with predominant tonic seizures with multifocal spikes in EEG. Seizures were refractory 97 to antiepileptic treatment but showed somehow a good response to i.v. phosphenytoin with several days of seizure freedom after phosphenytoin rescue therapy. Patient had poor eye contact and poor spontaneous movements with generalized hypotonia and brisk tendon reflexes. Extensive neurometabolic evaluation was normal and early MRI showed thinning of the corpus callosum. With time EEG evolved to a pattern of modified hypsarrhythmia without clinical transition to spasms. Patient continued with frequent tonic seizures up untill six months of age when seizures were finally controlled by a combinatinon of topiramate, lamotrigine and valproate. From the neonatal period on patient demonstrated a significant developmental delay. At the current age of 24 months she is still seizure free on valproate monotherapy with her EEG showing slowing with rare multifocal epileptic discharges. High resolution melt analysis and direct sequencing revealed a de novo c.787G>A missense mutation in SCN2A predicted to cause p.A263T change in domain I of Nav1.2 channel. Conclusion: We have identified a novel SCN2A missense mutation as the etiology for early-­‐onset epileptic encephalopathy further expanding the spectrum of clinical disorders caused by SCN2A mutations. P16 -­‐ 2021 Copy number variation involving ABCB1 gene in a child with epileptic encephalopathy – a role in pathogenesis and/or multidrug resistance? Quintas S, Moldovan O, Serafim S, Ávila M. Pediatric Neurology Unit and Department of Genetics, Centro Hospitalar Lisboa Norte -­‐Hospital de Santa Maria, Lisbon, Portugal -­‐ [email protected] Introduction: Rare copy number variations (CNVs) have recently been established has important risk factors for epileptic encephalopathies, although the establishment of a clear pathogenic role for the CNVs identified in individual patients might be conflicting. Clinical case: We report a three years old boy with an epileptic encephalopathy, beginning at 1,5 month with infantile spams, developmental retardation and an EEG showing multifocal epileptiform abnormalities. Since then he has been treated with several anti-­‐epileptics (valproate, topiramate, fenobarbital, vigabatrine, zonizamide, levetiracetam, lamotrigine, clobazam, rufinamide, clonazepam, phenytoin, carbamazepine and eslicarbazepine), in different associations, as well as pyridoxine, oral prednisolone and ketogenic diet, without seizure control. Nowadays he has daily head drops and tonic seizures, multifocal epileptiform activity and no focalizing ictal activity on EEG and since 30 months of age is under vagal nerve stimulation (plus zonizamide and phenobarbital), with a 50% reduction in seizure frequency. He has a global developmental delay and no other abnormalities on physical examination. An extensive etiologic workup was carried out, the following exams showing no alterations: cerebral MRI (twice, last one at 29 months age, 3 Tesla); metabolic evaluation, karyotype and CDKL5 gene mutations search. CGH array done at three years of age showed a CNV with probable clinical significance: a 4,14 Mb duplication of 7q21.11q21 13, involving the ABCB1 gene. Discussion: Various data support the hypothesis that the overexpression of antiepileptic drug transporters may play a pivotal role in drug resistance in epilepsy. P-­‐glycoprotein, encoded by the ABCB1 gene might mediate at least part of the resistance, although some conflicting evidences exist for the role of known ABCB1 polymorphisms in antiepileptic drug resistance. The authors discuss the etiologic role of the large CNV found in the epileptic encephalopathy of this patient and/or in his refractoriness to anti-­‐ epileptic drugs, since it involves the ABCB1 gene. P17-­‐ 2103 Early epileptic encephalopathies associated with STXBP1 mutations: three new patients with different electroclinical profile evoluting to infantile spasms Barcia G, Chemaly N, Van Bogaert P, Gobin S, Barnerias C, Kaminska A, Munnich A, Desguerre I, Dulac O, Nabbout R. Department of Neuropediatrics, Centre de Reference des Epilepsies Rares, Inserm U663, Hopital Necker Enfants Malades, Paris Descartes University, Paris, France -­‐ [email protected] Mutations in STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, have first been reported in early onset epileptic encephalopathy with suppression-­‐bursts (Saitsu, 2008), then in infantile spasms (Otsuka, 2010) and in patients with non syndromic mental retardation without epilepsy (Hamdan, 2010). We report the electroclinical profile of three patients with three novel de novo STXBP1 mutations presenting with infantile spasms after three different evolutions. Patient 1, born premature at 26 weeks of gestational age, presented infantile spasms with hypsarrhythmia at age of 4 months not preceded by other seizure types. She presented normal EEG background before epilepsy (performed for premature follow-­‐up) onset with no spikes neither suppression burst pattern. IS were pharmacoresistant till the age of two years when seizures progressively stopped. The child, actually aged of three years, is seizure-­‐free and presents a profound mental delay. Patient 2 presented focal motor seizures since the age of 2 months associated to focal abnormality on EEG with normal background activity. At 3 months spasms in series appeared and EEG showed hypsarrhythmia. At two years, the child has ongoing seizures (spasms) despite many AEDs trials. He presents with a severe psychomotor delay. Patient 3 presented infantile 98 spasms at age of 1 month associated to suppression burst pattern with evolution to hypsarrhythmia. Seizure responded to treatment and since the age of two years the patient is seizure-­‐free. Actually, at the age of 13 years, she presents a profound mental delay with autistic traits. Two of our patients did not presented with suppression burst pattern and in one case, EEG was normal before the onset of spasms. These cases emphasize the place of STXBP1 analysis in infantile spasms. P18 -­‐ 2040 A series of epileptic encephalopathies: an array-­‐based genotype-­‐phenotype correlation in a turkish cohort of children Topcu M, Konuskan B, Alikasifoglu M, Aktas D. Unit of Pediatric Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey Background: Epileptic encephalopaties are characterized by an epilepsy with the first week of life, severe developmental delay and usually a poor prognosis. Determining the underlying etiology responsible for infantile epileptic encephalopathy is a clinical challenge worth undertaking to facilitate advice on the recurrence risk and to allow the option of prenatal testing. Methods: To determine molecular pathology in 15 patients with epileptic encephalopathy, array-­‐based comparative genomic hybridization (array-­‐CGH) were performed on DNA’s from the patients. Results: Deletion of ARFGAP1, CHRNA4 and KCNQ2 genes on 20q13.3; deletion of GRINA and PLEC genes on 8q24.3; deletion of the SCN gene cluster on 2q24.4; deletion of DTNB gene on 2p23.3-­‐24.3; duplication of EHMT1 on 9q34.2-­‐34.3; duplication of DCX gene on 6p22.3-­‐22.3; duplication of GRIK5 on 19q13.2-­‐13.31; duplication of BRD2 gene on 6p22.1-­‐22.3; duplication of KCNQ1 on 11p15.4; duplication of DOC2A, QRT and SEZGL2 on 16p11.2, duplication of NTAN1 on 16p13.1 were observed in our patients. Conclusion: We performed an array-­‐CGH study to the patients with epileptic encephalopathy, found the genomic rearrangements affecting disease-­‐causing and genes involve pathways. The success of our preliminary array-­‐CGH study allows us to expand the cohort. According to the available literature, this is the first comprehensive array-­‐CGH evaluation of a Turkish cohort children with epileptic encephalopathy. P19 -­‐ 1501 Long term accidental overdose of levetiracetam in an infant Ozkale Y, Ozkale M, Saygi S, Erol I. Baskent University Faculty of Medicine, Department of Pediatrics, Adana, Turkey -­‐ [email protected] Introduction: Levetiracetam is one of the new anticonvulsant drug which has a high therapeutic index and potential antiepileptogenic effects. Herein, we report a patient with multidrug refractory epilepsy and Ohtahara syndrome who was accidentally administered 300 mg/kg/day for 35 days by her mother. Case report: A 10-­‐
month-­‐old female was admitted to the Baskent University Hospital, Adana, Turkey due to an overdose of levetiracetam. She had been followed by our child neurology department from the newborn period as she suffered from Ohtahara syndrome. She was treated with vigabatrin, topiramate, calcium folinate, vitamin B6 and levetiracetam. She was accidentally administered 10 times the recomemended dosage of levetiracetam by her mother and remained on this dosage for 35 days. At physical examination, the infant’s vital signs were normal. Neurological examination revealed apathy and profound hypotonia with brisk deep tendon reflexes. Laboratory testing revealed the following: leukocyte count, 13700/mm³, hemoglobin, 11.8 g/dl; platelet count, 359,000/mm³. Liver and kidney function tests and serum electrolyte levels were normal. She was hospitalized for observation of levetiracetam adverse effects. Treatment with vigabatrin, topiramate, calcium folinate, and vitamin B6 were continued. Her apathy resolved within 2 days and we did not observe any other side effects. Her laboratory analyses showed no abnormalities in blood chemistry or complete blood count. The girl was discharged after 7 days with her usual dose of levetiracetam. Conclusion: To our knowledge, the present case is the youngest child to have received a long-­‐term levetiracetam overdose. Accidental levetiracetam overdose in children and even in infants requires discontinuation of the drug, without any changes in safety or efficacy. In addition, re-­‐administration of the drug at the correct dosage in our patient resulted in no adverse effects. P20-­‐ 2138 Use of perampanel in 2 children with refractory focal epilepsy Mewasingh LD, Varadkar S, Buonaiuto K. Imperial College Healthcare NHS Trust, London, United Kingdom -­‐ [email protected] Case 1: A 15 yr old girl developed childhood onset Herpes Simplex encephalitis with extensive bitemporal involvement resulting in refractory epilepsy, learning difficulties and frontal executive problems. Her daily focal seizures have proven drug-­‐resistant with multifocal discharges on EEGs. She was awaiting VNS placement (not a candidate for epilepsy surgery). Perampanel was added to her AEDs (keppra and zonisamide), with significant 99 improvement in seizure control at 4 mg. For the first time the patient was having 2 weeks seizure interval. At doses of Perampanel 6 mg, worsening of seizures was noted. Currently she is maintained on 4 mg nocte, her VNS is being deferred and zonisamide being weaned off. Both parents and the young person are pleased with the above outcome. Case 2: This 14 yr old girl has multiple cavitating brain lesions in keeping with latent CNS TB. She has a single lesion in her R mesial temporal lobe, which is the focus of her focal seizures. Given drug interaction with her anti TB medications her antiepileptic drug regime was modified, consisting of Lamotrigine with perampanel recently added at 2 mg. Her seizures remain frequent and on a daily basis with plans to increase Perampanel to 4 mg and eventually 6 mg nocte if tolerated. She is within the epilepsy surgery work-­‐ up programme. Neither patient has had dizziness on perampanel. Discussion: Perampanel is a new antiepileptic medication licensed for children > 12 years old, with a novel mechanism of action as a non-­‐competitive AMPA receptor antagonist on the glutamate receptor of post-­‐synaptic neurons. In the first case its efficacy resulted in VNS being deferred; whilst in the second case a clear response is yet to be demonstrated. As further experience in its use is obtained, the role of Perampanel in drug resistant childhood epilepsy will become clearer. P21 -­‐ 2126 The vitamin D deficiency in patients with newly diagnosed idiopathic epilepsy F.Mujgan Sonmez, Ahsen Donmez, Metin Canbal, Mehmet Namuslu. Turgut Ozal University, Faculty of Medicine, Dept of Child Neurology, Ankara, Turkey -­‐ [email protected] Objective: Vitamin D is a hormon and there are some roles in calcium and bone homeostasis, cell proliferation. Also, recent studies indicates that vitamin D and its receptors play an important role in the brain. Several studies shown a link between vitamin D deficieny and epilepsy. In this study, we investigated the 25-­‐OH Vitamin-­‐D3 levels together with other bone markers (Calcium, phosphorus, alkaline phosphatase and Parathormon in patients with idiopathic epilepsy. Metod: During the 2011 September-­‐2012 November, This study included 60 patients (34 females and 26 males) with idiopathic epilepsy whose ages change between 5-­‐16 years (the mean age was 9,6 +-­‐ 3,2 years) and 49 healthy child (25 females and 24 males, aged between 5-­‐16 years). We retrospectively analized laboratory records of the patients and evaluated the levels of calcium, phosphorus, alkaline phosphatase, PTH and 25-­‐OH Vitamin-­‐D3. Exclusion criteria included mental retardation, previous history of status epilepticus, previous history of AED use, skin, liver, gastrointestinal , bone or kidney disease. The levels under 20 ng/ml were described as vitamine D deficiency. Result: There was no significant difference in the age, gender distribution and levels of Calcium, Phosphor, alkaline phosphatase and PTH. The levels of 25-­‐OH Vitamin-­‐D3 showed a statistically significant decrease compared to the control group. Conclusion: The results of this study demonstrated that vitamine D may play important role in epileptic patients. The next step would be to investigate the relation of the low vitamine D levels and supplementation therapy to the outcome of epilepsy. P22-­‐ 2098 Sleep EEG recordings in childhood absence epilepsy spectrum Tsirouda AM, Dinopoulos A, Mponakis A, Pons R, Paschalidou M, Pavlopoulou I, Tsoumakas C. 3rd Department of Pediatrics University of Athens, “Attikon” University Hospital, Greece -­‐ [email protected] Objectives: Childhood absence epilepsy is a common pediatric epileptic disorder at the age of 2-­‐ 10 years old. It is characterized of gradually increase of absence seizures in combination with automatisms. Several epileptic syndromes have absences as the only or most predominant seizure type and their EEG-­‐patterns are quite similar. The EEG-­‐patterns conclude generalized 2.5-­‐4Hz spike and slow-­‐wave discharges. The episodes always occur during hyperventilation and some syndromes demonstrate photosensitivity. The purpose of the research is studying the interaction between sleep architecture and epileptic discharges in patients with absences. Materials and Methods Twenty children between the age of 3.5-­‐14 (mean=611/12) years old (70%female) with typical or atypical absences were studied. Routine-­‐eeg including hyperventilation (5min), photic stimulation and sleep polysomnography were performed before the onset of drug treatment. Results Fourteen children (70%) were diagnosed with CAE, 3 with JME,2 with MAE and 1 with EMA. Eight children (40%) were treated with valproic acid. Ethosouxomide, lamotrigine or combination was used for the rest. All children showed 3-­‐4Hz generalized SWD with bifrontal locate during hyperventilation (mean time of absence occurrence=103,5 seconds) and 4 had photosensitivity. The discharges were recorded in all children’s sleep mostly in stages I, II of NREM. Activation of the discharges is observed during stages II and SWS, thus there is a fragmentation of the epileptic complexes and attenuation of epileptic activity during REM-­‐sleep. Partial discharges were recorded in 50% of children with different localization. The mean of discharges (either generalized or partial) per hour during the sleep study was approximately 35 epileptic discharges per hour (less=20,92, most=82,16). Conclusions: There is a qualitative and quantitative change of electrographic activity during sleep in children with childhood absence epilepsies. Further 100 longterm and comparative research should be conducted 6 months and 1 year after treatment onset in order to estimate possible changes in sleep. P23 -­‐ 2094 Increasingly focal loss of regeneration in a patient with BECTS developing a CSWS with partial subsequent recovery under steroids; a longitudinal case study with fMRI, night-­‐EEGs and neuropsychology Bölsterli Heinzle BK, Oser N, Critelli H, Nageleisen-­‐Weiss A, Schmitt B, Schneider JF, Huber R, Datta AN. Pediatric Neurology Department, University Children's Hospital Zürich, Switzerland -­‐ [email protected] Objectives: We demonstrate the course of regression with loss of nocturnal regeneration due to epilepsy in a child with BECTS evolving to CSWS with partial recovery. Methods: Sleep deprivation EEG at 8.5 years; 4 night EEGs at 9.0, 9.5, 9.75 and 10 years with sleep slow wave slopes (from first to last hour of sleep) as a marker of nocturnal regeneration; Language fMRI at 9.5 years; neuropsychological testings at the age of 8.7, 9.0 and 9.75 years. Results: Initially right hemispheric centro-­‐temporal sharp waves at 8.5 years became bilateral at 9 years. Slow wave slope analysis showed a reduced slope change in both left and right hemispheric foci (-­‐2.6%) and a normal one in the rest of the brain (-­‐28.0%). Language functions decreased with no clearly visible negative impact in school performance. Regression signs came up at 9.5 years. CSWS was confirmed; slow wave slope analysis revealed a loss of regeneration with an increasing slope (+5.6%) in both foci and a reduced regeneration in the rest of the brain (-­‐6.8%). Steroids were initiated. 3 months later, the patient regained normal school performance and neuropsychological testing improved. Despite seizure freedom slow wave slope change even got worse in both foci (+11.4%) and in the rest of the brain (+2.4%). Steroid treatment was continued for other 3 months. After that, EEG showed a clear decrease of nocturnal epileptic activity with an improvement of the slow wave slope change. Conclusion: A girl with BECTS developed a CSWS with a complete loss of regeneration in both foci and decreased regeneration in the rest of the brain. Neuropsychological testing anticipated left hemispheric dysfunctions 5 months prior to regression. Steroid treatment improved school performance, led to seizure freedom. Nocturnal regeneration only improved after 6 months of steroids indicating most probably the delay of neuronal recovery. P24 -­‐ 2085 Experience and clinical utility of prolonged video-­‐EEG monitoring in pediatric patients of a tertiary center Sampaio M, Rocha R, Castro A, Pires I, Leão M, Augusto-­‐Ribeiro J. Neuropediatrics Unit, Hospital Pediátrico Integrado, Centro Hospitalar S. João, Porto, Portugal -­‐ [email protected] Introduction: Prolonged video-­‐EEG (vEEG) monitoring is a valuable tool in the evaluation of paroxysmal events and it is usually done in epilepsy monitoring units. However, in the context of limited financial resources, prolonged vEEG monitoring performed in the pediatric ward may also be effective and useful to characterize paroxysmal events and epilepsy. Objectives To evaluate the clinical utility of prolonged vEEG monitoring in patients with paroxysmal events, performed in the pediatric ward of a tertiary center. Materials and Methods: Retrospective study of clinical and vEEG reports of patients submitted to prolonged vEEG monitoring from September 2011 to March 2013. EEG NicoletOne LTM® equipment was used. Analysed data included demographic and clinical characteristics and utility of monitoring (success in the registration of typical events, diagnosis of events and impact in subsequent management). Results: A total of 58 sessions were performed for a sample of 53 patients, with a median age of 5 years (1 month to 17 years) and 29 (55%) were male. The median length of stay was 2 days (12 hours to 5 days). Forty-­‐six sessions (79%) were clinically useful, 25 for paroxysmal disorders/events, and 21 for epilepsy. The majority of events was registered with good video and EEG quality. The range of events per session was 4 to 28, with a mean of 20 events per patient. Following monitoring, antiepileptic therapy was discontinued in 3 patients. Conclusions: Prolonged vEEG monitoring is an useful method in the evaluation of patients with paroxysmal events, differentiating epileptic versus nonepileptic phenomena, with consequent clinical decisions. Our results confirm its utility in the daily clinical practice of a neuropediatrics unit. P25-­‐ 2072 Diagnostic clues and difficulties in Dravet Syndrome starting from 34 Dravet patients analysis within Romanian Research Group for Rare Genetic Epilepsies Craiu D, Barca D, Burloiu C, Butoianu N, Deconinck T, Gos M, Hoffman-­‐Zacharska D, Iancu D, Minciu I, Motoescu C, Sandu C, Tarta-­‐Arsene O, Weckhuysen S, Iliescu C. „Carol Davila” University of Medicine, Department of Neurology, Pediatric Neurology, Neurosurgery, Psychiatry -­‐ Pediatric Neurology Clinic No.II, Bucharest; Pediatric Neurology Department, Al. Obregia Hospital, Bucharest, Romania -­‐ [email protected] 101 Objectives: Although clinical and genetic spectrum of Dravet Syndrome are currently intensively studied, there are still undiagnosed or delayed diagnosed cases. We present pitfalls and diagnostic clues starting from cases studied by the Romanian Epilepsy Network and Romanian Research Group for Rare Genetic Epilepsies within RES Consortium EuroEpinomics. Materials and Methods: 34 Dravet phenotype patients selected from Romanian databases in the project 6EUROC, partner of RES EuroEpinomics Consortium were studied concerning age and modality of onset, clinical, EEG, imaging and genetic aspect. Results: One case with slight facial hipoplasia and cheiloschisis associating cortical malformation and nodular periventricular heterotopia had delayed diagnosis of Dravet syndrome despite typical early onset prolonged focal seizures with fever on both sides. Vaccination associated short seizure at onset was diagnostic clue in a prematurely born child with global developmental delay, with subsequently resistant epilepsy. SCN1A mutations were demonstrated. Ethical issues were raised by cases with single focal febrile status epilepticus in normally developed infants. Diagnosis delay varied from 0 to 3 years after the first seizures. Afebrile seizures were present at onset in 3 cases. Patients with newly identified mutations did not associate a particular phenotype. Conclusions: Association of structural pathology (migration disorders or post-­‐hipoxic-­‐ ischaemic lesions) does not exclude Dravet syndrome diagnosis (with SCN1A mutation). Vaccination associated seizures and/or prolonged unilateral seizures in infants should raise suspicion for Dravet phenotype. Testing for SCN1A mutation in an infant with normal development after the first focal febrile status epilepticus is debatable from the ethical point of view. P26 -­‐ 2068 Epilepsy and learning disorders Charollais A, Rolland A, Lemarchand M, Marret S, Neuropediatrie Medecine neonatale, Rouen, France -­‐ [email protected]­‐rouen.fr Benign idiopathic epilepsies are frequent in children. Recently, specific neurocognitive disorders have been reported as being associated with type of benign epilepsy and localization. We report the case of a young boy who consulted for global learning disorders. Examination revealed low activity benign focal epilepsy with centrotemporal spikes, associated with very slight activation during sleep. Following 10 month of treatment with a 20mg per kg dose of valproate, neurocognitive assessment revealed a 22 point and 5 point rise in non verbal and verbal skills respectively. The young patient received concomitant speech therapy, but there was already a clear overall improvement in his visual attention. His Eeg measurement improved however there was persistence of spike and wave rushes with some night-­‐spikes without activation. He is currently a pupil at a mainstream secondary school, whereas 4 years previously he had been under consideration for referral to a special school. There is little evidence in the literature that treatment of electroencephalographic abnormalities impacts on learning and in particular on oral language. Nevertheless, case by case analysis confirms the need to record sleep patterns to identify the neurocognitive disorder in question and even for older children. The prognosis for benign epilepsy remains positive. Nevertheless, benign epilepsy can result in serious neurocognitive disorders, which must be taken into consideration during the basic learning phase. Individualized treatment is therefore mandatory for children with benign epilepsies. P27 -­‐ 2058 Effect of levetiracetam monotherapy on lipid profile in children with epilepsy: a prospective study Paschalidou M, Attilakos A, Garoufi A, Tsirouda M, Papadopoulos I, Dinopoulos A. 3rd department of Pediatrics, University of Athens, "Attikon" University Hospital, Greece -­‐ [email protected] Objectives: Antiepileptic drugs, such as carbamazepine, often increase the serum concentrations of serum lipids. Studies evaluating the effect of levetiracetam (LEV), a newer broad spectrum antiepileptic agent, on serum lipid levels are very limited. The aim of this study was to investigate prospectively the effect of LEV monotherapy on serum lipid profile in children with epilepsy. Materials and Methods: The study population consisted of 20 children (8 males, 12 females, aged 2 to 15 years old, mean age 6,5±4,16 years) with epilepsy treated with LEV monotherapy. None of the children were receiving any form of AED medication prior to LEV initiation. Serum total cholesterol (TC), low-­‐density lipoprotein cholesterol (LDL-­‐C), triglycerides (TGs), high-­‐density lipoprotein cholesterol (HDL-­‐C), apolipoprotein A-­‐I (apo A-­‐I), apolipoprotein B (apo B) and lipoprotein (a) [Lp(a)] were evaluated in all children, before and at 2 and 6 months of LEV monotherapy. Results: TC and HDL-­‐C were significantly increased at 6 (p=0.011 and p=0.012, respectively) months of LEV treatment. There were no significant alterations in LDL-­‐C, TGs, apo A-­‐I, apo B and Lp(a) levels during the study. Conclusions: LEV monotherapy may cause significant alterations in TC, and HDL-­‐C levels in children with epilepsy, occurring early in the course of treatment. Long-­‐term, large, prospective studies are required to clarify the possible effect of LEV on serum lipid profile, the underlying mechanisms involved and its clinical significance. 102 P28-­‐ 2016 Cognitive and behavioural study of 24 consecutive patients with a Dravet syndrome Villeneuve N, Laguitton V, Viellard M, Lepine A, Chabrol B, Dravet C, Milh M. Pediatric neurology unit, Timone children Hospital and Henri Gastaut Hospital, Marseille, France -­‐ [email protected]­‐hm.fr Aim: To describe cognitive and behavioural profile of 24 patients with Dravet syndrome (DS). Methods: We administrated Weschler intelligence scale and Vineland scale between the age of six and ten, in 24 patients with DS followed in our institution. Statistical analysis (Spearman rank order and Pearson correlation coefficient) were used to correlate epilepsy characteristics with the cognitive state. Results: SCN1A was mutated in 22 patients out of 24. After the age of 6 years, none of DS patients had a normal IQ using WISC. When interpretable, their cognitive profile was characterized by an attention deficit, an inability to inhibit impulsive responses, perseverance and deficit in planning function. Administrating Vineland scale in 23 patients, we showed that socialisation skills were significantly higher than communication and autonomy skills. We did not find any significant correlation between the developmental quotient assessed between 6 and 10 years of age and the majority of epilepsy characteristics during the first two years in this small group of patients. Interpretation: An impairment of executive function may explain most of the behavioural and cognitive phenotype of the DS patients. The severity of the cognitive impairment is mostly due to low communication and autonomy capacities, whereas the socialisations skills are relatively preserved, in contrast to autism. P29 -­‐ 2013 Temporal Lobe Epilepsy (TLE) in Children: Etiologies in a cohort of 20 Tunisian patients Abid I, Ellouz E, Hsair I, Ayedi I, Kammoun F, Triki C. Child neurology department, Sfax, Tunisia -­‐ Introduction: The etiology of TLE in different children cohorts have been infrequently studied. The aim of this study is to analyze the data of 20 children diagnosed with TLE in order to describe the etiology of TLE in children. Methods: A retrospective clinical, electric and radiological analysis was carried out on children diagnosed with TLE seen in the neuropediatric department of Hedi chaker Hospital-­‐Sfax (Tunisia). All patients had neurological examination, cerebral MRI with axial and coronal T1, T2 weighted images, and at least one EEG. Results: Our patients were divided into three groups according to likely etiology: Group1 (G1) with 10 patients (50%) with symptomatic TLE due to cortical malformations or non-­‐progressive tumors: 4 children had focal dysplasia, 2 had other located focal malformation, 3 had glial tumors, and one had cavernoma. Group 2 (G2) consisted of 4 children (20%) with mesial temporal sclerosis in MRI, and group 3 (G3) comprised 6 patients (30 %) with no abnormality in neuroimaging and no significant antecedents (cryptogenic TLE). Patients including into G2 and G3 had pharmaco-­‐resistant epilepsy and had psychological problems such as mental retardation or learning disabilities. Conclusions: Etiology differences between children with TLE may have prognostic implication; in fact in our series, G1 and G2 were statically associated with poor outcome .We found this classification very useful in the assessment of patients with TLE. P30 -­‐ 2008 Treatment of Dystonia and Epilepsy in 3 Patients with ARX-­‐Mutations Selch C, Wohlrab G, Hackenberg A, Bast T, Biro A, Hasse A, Berweck S, Staudt M, Kluger G. Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany -­‐ [email protected]­‐kliniken.de Objectives: Mutations in the X-­‐chromosomal ARX (Aristaless-­‐Related-­‐ Homeobox) gene cause both nonsyndromic and several forms of syndromic mental retardation. The phenotypes are characterized by pleiotropy. Common clinical features include epilepsy, brain malformations, genital abnormalities and dystonia. Dystonia has previously described as a clinical feature in patients with ARX mutations, however, there is hardly any information about antidystonic treatment in affected patients. Methods: retrospective evaluation of 3 out of 4 patients (3 male patients, age 4-­‐ 17, including one pair of brothers) with ARX-­‐mutations presenting with dystonia and epilepsy. 1 patient had epilepsy but no dystonia. Results: Gene analysis in the pair of brothers showed identical 21bp GCG repeat expansions in exon 2 of the ARX gene c.333_334ins(GCG)7, leading to an expansion of the first of four alanine tracts. The third patient was found to be hemizygous for a previously not described de-­‐novo mutation with duplications in the alanine repeats c.315_335dup; p.Ala109_Ala115dup. All patients had infantile spasms with onset at 4-­‐6 months and further developed generalized tonic-­‐clonic seizures. Epilepsy was treated with multiple antiepileptic drugs including benzodiazepines, barbiturates, steroids, valproic acid, vigabatrin, levetiracetam and oxcarbazepine. All patients responded to combination therapy including VPA, 2 became seizure free. Dystonia in all patients presented in the first months of life. One patient developed severe status dystonicus at the age of 10 years. Dystonia was successfully treated with tetrabenazine (1/3), oral baclofen (3/3), intrathecal baclofen (1/3) and L-­‐DOPA (1/3). Conclusion: Dystonia is an important clinical feature 103 in some patients with ARX mutations. Dystonic symptoms may present even before the onset of epilepsy in early infancy and may be difficult to differentiate from epileptic seizures. Successful therapeutic options include baclofen, administered orally or even intrathecally. No general conclusions can be drawn from this case evaluation but may give an impulse for collaborated clinical observations and data collections. P31 -­‐ 2001 Refractory epilepsy and retinal involvement in a patient with ring chromosome 14 Deconinck N, Diakogeorgiou A, Pelc K, Monnier A, Deleener A, Sznajer Y. Neurology, HUDERF, ULB, Belgium -­‐ [email protected] Background To date less then 100 patients identified with a Ring chromosome 14 have been published so far [Ref 1]. Standard karyotype leads to the identification of ring chromosome 14 whereas different breakpoints and size of deletion have now been confirmed using molecular karyotype technology. Parent of origin effect may modulate phenotype (imprinting). Intellectual disability which is almost always severe is not related to the size of the deletion but rather to the severity of epilepsy [Ref 2] Dysmorphic features are reported to be distinctive with a ‘long and sometimes asymmetric face’, full cheeks, high forehead, horizontal eyebrows; short and bulbous nose). Characteristically, abnormal eye features (abnormal retinal pigmentation, Drüsen, ‘abnormal macula’, strabismus) are associated with more proximal deletion 14q11.2 band encompassing NRL and RPGR1P1 genes. Natural History A girl of unrelated healthy parents was admitted to neurologic dept for seizure at the age of 11 months. Pregnancy and delivery were unremarkable but for neonatal isolated microcephaly (-­‐2SD). OFC remained along -­‐2SD. Development was noted to be normal. Seizures became progressively refractory to treatment while work-­‐up did not identify brain anatomic malformation as any other anatomic malformation. Ophthalmologic exam identified unspecified retinal pigmentation anomaly with small Drüsen; eye contact was poor. Important intellectual disability, and particularly expressive language delay were recorded. She is very smiling and has a pleasant personality. Standard karyotype identified r(14) in all cells. Conclusions Patients with r(14) develop a distinctive spectrum of phenotype as epileptic history. Long term follow-­‐up with special care to seizure, education and ophthalmologic involvement can be guaranteed. Additional investigation are still required to better understand variable expressivity, gene haplo insufficiency, second allele involvement as for a possible role of imprinting. P32 -­‐ 1982 Clinical impact of long-­‐term nocturnal home monitoring for detection of epileptic seizures in pediatric patients Van de Vel A, Cuppens K, Bonroy B, Milosevic M, Van Huffel S, Vanrumste B, Lagae L, Ceulemans B. Antwerp University Hospital – University of Antwerp, Belgium -­‐ [email protected] Objective: The gold standard for detecting epileptic seizures is video/EEG, but its discomfort does not allow long-­‐
term home measurement and analysis is not yet automated therefore does not allow real-­‐time alerts. Our team has developed a system based on three-­‐axial accelerometers (ACM), radar and video. The aim of this study is evaluating its efficiency, comfort and user friendliness in a long-­‐term home situation. Material and methods: The system consists of a camera, IR source and radar attached to a pole that is placed in the corner of the patient’s room, four wireless ACM attached to the patient’s wrists and ankles using elastic bracelets, and a laptop receiving (through Bluetooth), processing and storing recordings that contain movement. So far we have monitored four patients for one month and obtained at least 17 nights with complete data for each patient. Before applying the algorithms that our team developed for different seizure types (see EPNS 2011), we started analyzing the data offline for extraction of long and intense movement and used video verification for confirmation of suspected seizures. Results: As our data do not contain EEG signals, the control sets of seizures are those recorded by the caregivers who are surveillancing the patient on a semi-­‐continuous basis, with or without audio-­‐based detection. For all four patients, more seizures of different types have been found after data analysis than noticed by the caregivers. Conclusions: Long-­‐term measurement of epileptic seizures and discussion of results with the patient’s physician, caregiver and parents has lead to valuable feedback for improvement of our system towards user friendliness, comfort and utility. The efficiency of the system has been proven by the fact that more than the witnessed seizures have been detected, but needs to be further explored by measuring other patients. P33-­‐ 1977 Seizure and cognitive outcomes of epilepsy surgery for glioneuronal tumours in childhood: the timing of intervention Ramantani G, Kadish NE, Anastasopoulos C, Strobl K, Stathi A, Brandt A, Mayer H, Wagner K, Schubert-­‐Bast S, Korinthenberg R, van Velthoven V, Zentner J, Schulze-­‐Bonhage A, Bast T. Epilepsy Centre, University Hospital Freiburg, Germany -­‐ [email protected]­‐freiburg.de 104 Purpose: To investigate the seizure and cognitive outcomes of children and adolescents undergoing resective surgery for glioneuronal tumor-­‐related refractory epilepsy and determine their predictive factors, with an emphasis on time-­‐related variables. Methods: We retrospectively analyzed the findings of presurgical evaluation, resection types and outcomes over 1.3-­‐12.3 years (mean 7.3) of 29 consecutive children and adolescents who underwent resection at the Epilepsy Center Freiburg in 2000-­‐2011. The mean age at epilepsy onset was 7.9 years (range 0-­‐15.4), the mean age at surgery was 11.7 years (range 2.6-­‐17.3), and the mean epilepsy duration was 3.8 years (range 0.3-­‐15.3). Aetiology comprised 13 dysembryoplastic neuroepithelial tumors and 16 gangliogliomas, with additional focal cortical dysplasia in 5 cases. Results: 86% of children were seizure free 12 months after surgery and 76% remained seizure free at final follow-­‐up; 62% discontinued antiepileptic drugs. Gross-­‐total resection was related to significantly higher rates of seizure-­‐freedom. Higher presurgical cognitive functioning (full scale IQ, verbal IQ) was related to shorter epilepsy duration independent of age at epilepsy onset, thus determining postsurgical functioning. Overall, improvements in verbal IQ, performance IQ and visual memory as well as a trend towards improvement in full scale IQ were established after surgery. No deterioration in any of the cognitive variables was noted on a group level. Conclusion: With completeness of resection predisposing to favorable outcomes regarding seizure alleviation, a short latency to surgery appears crucial in preserving cognitive functions, thus supporting early surgical intervention. P34 -­‐ 1967 Developing paediatric EEG in urban and rural settings in Rwanda Dan J, Pelc K, Muganga N, Van Steirteghem S, Lepage P, Binagwaho A, Cheron G, Dan B. Ecole Polytechnique, ULB, Brussels, Belgium -­‐ [email protected] Paediatric epilepsy has been increasingly recognised as a health care priority in Africa. High prevalence is related to predisposing factors such as perinatal insult, infectious disease, traumatic brain injury and other brain stressing factors. Availability of antiepileptic drugs may vary widely depending on the place and time. However, supplies of cheaper drugs such as phenobarbitone and phenytoin are often sufficient. In Rwanda, carbamazepine, sodium valproate, benzodiazepine and sometimes other antiepileptic drugs can also be prescribed. Still, there is a high prevalence of complications related to seizure disorder. A major difficulty relates to diagnosis. Access to electroencephalographic equipment, which is regarded as indispensable in high-­‐income countries is at best scarce. We aimed to assess the feasibility of low-­‐ cost wireless electroencephalography in urban and rural settings in Rwanda. We adapted a 14-­‐channel recording system originally designed for brain-­‐ computer interface primarily used in video gaming. Clinical EEGs were recorded in 30 children aged between 15 months and 15 years with various presentations (including epilepsy, cerebral palsy, developmental delay and absence of neurological disorders) either in city hospital or rural health care centres in Rwanda. Nursing personnel was trained to place the headset according to a standard protocol, verify electrode impedance, perform the recording, and transfer the raw digital data via internet (either locally or transporting a flash disc according to available facilities) to a server. Data was processed using a dedicated software that we developed for medical analysis of EEG traces. We listed caveats and limitations and designed strategies to overcome them. We conclude that EEG can be recorded in children in rural and urban Rwanda by health care personnel using low-­‐cost hardware and internet facility (or transport of compact digital drive), and analysed centrally in a hospital centre with possible remote support. P35-­‐ 1937 A new variant detected in GRIN2Aby whole-­‐exome sequencing in a patient with intellectual disability with intractable epilepsy Per H, Caglayan AO, Canpolat M, Bilguvar K, Gümüþ H, Kumandas S. Department of Pediatric Neurology, Medical Faculty, Erciyes University, Kayseri, Turkey -­‐ [email protected] Objectives: A six year old female patient was submitted to our clinic due to mild intellectual disability, interactible epilepsy and delayed speech. She was born at 37-­‐gestational week with 2950gr birth weight. During the nonatal period, she had feeding difficulties and vomitting. She was hopsitalized due to polycythemia, hypoglycemia, congenital hypothyroidea and asphixia. On her EEG, epileptic encephalopathy was detected and antiepileptic therapy was started with valproate, pyridoxine, lamotrigine, clobazam, clonazepama, clonazepam, fenytoin, sulthiame, levetiracetam, vigabatrin, carbamazepine, rufinamide, ethosuximide, primidone, zonisamide, synacthen, IV Ig and ketogenic diet according to the seizure type. An internal shunt was implanted due to symptomatic frontal arachnoid cyst. TANDEM Mass spectroscopy and urine organic acids were normal Materials and Methods: To assess the underlying genetic defect, we performed whole exome sequencing on the patient. Results: We identified heterozygous missense variant mutation (R1285K) in GRIN2A, mutation of which 105 are responsible from epilepsy and neurodevelopmental defect syndrome (OMIM:613971). Conclusions: Here we describe the first Turkish patient diagnosed with this rare disorder through whole-­‐exome sequencing. 106 P36-­‐ 1936 The effects of valproic acid monotherapy on the body’s vitamin K status in children Adnan Ayvaz, Dilara Ýçaðasýoðlu. Þanlýurfa, Turkey -­‐ [email protected] Introduction: Our study aims to investigate Vitamin K reserves in children using valproic acid (VPA), a subject not formerly reported in the literature, and the effects of VPA use for a period of one year on Vitamin K reserves. Material And Method: The study conducted prospectively at the Cumhuriyet University, Turkey over a period of one year included 25 children (14 male, 11 female) aged between 4 to 17 who received antiepileptic drugs (VPA) for the first time and continued the therapy with this single drug. Patients were divided into two stages as pre-­‐
puberty and puberty according to Tanner’s criteria, and the ratio of carboxylated osteocalcin and undercarboxylated osteocalcin were measured using the ELISA method both pre-­‐therapy and one year post-­‐
therapy. Findings: Although carboxylated osteocalcin demonstrated a minimal increase in the pre-­‐puberty group, it was observed to decrease in the puberty group. We noted that, although higher in the pre-­‐puberty group, undercarboxylated osteocalcin was observed to decrease compared with their start values in both groups. Discussion: The results of our study demonstrate that the body’s Vitamin K reserves tended to decline in our puberty group patients, that there was a weakened capacity to meet the need, and that the bone metabolism was negatively affected. P37 -­‐ 1895 Association of Down syndrome and epilepsy with atypical absences and astatic seizures Dica A, Acinte I, Tarta Arsene O, Barca D, Iliescu C. Department of Pediatric Neurology, Clinical Hospital "Al. Obregia", Bucharest, Romania -­‐ [email protected] Purpose: Down syndrome (DS) it is the most common genetic condition characterized by a supplementary 21 chromosome usually from the mother side. Association with epilepsy was described in 1.4-­‐17% of children with DS. Most frequent types of epilepsy in childhood are infantile spasms. Our aim is to present 2 cases of girls with DS and epilepsy with generalized seizures, with astatic seizures and atypical absences respectively, with an extremely prompt response to levetiracetam. Methods and results: Case 1: 3 years old girl with DS, with onset of epileptic spasms at 5 1/2 months old, remitted after synthetic ACTH, at 14 months. Severe developmental delay with autistic traits. Onset of astatic seizures at 1 year 9 months old, daily, frequent, interictal EEG showed generalized spikes and waves and polispikes waves discharges, no clinical events. Cerebral MRI showed a small right lenticular lacunae. Extremely prompt response to levetiracetam, clinically and on EEG. Case 2: 7 years old girl with DS and moderate developmental delay. One febrile seizure at 1 year old. Onset of seizures at 6 years 3 months old, with features suggesting atypical absences -­‐ staring, eyelid blinking, slight chewing, unresponsiveness, hiper/hipotonia, duration -­‐ seconds. EEG trace showed bilateral spikes and waves discharges with associated clinical events -­‐ as described before, 5 seconds. Levetiracetam was started with a spectacular response -­‐ seizure control from the first doses. Conclusion: We wanted through this paper to highlight the association of DS and epilepsy with generalized seizures -­‐ astatic seizures, atypical absences -­‐ and the prompt response of our cases to levetiracetam. Taking into consideration these facts, we consider that levetiracetam could be the first choise for children with such seizures, and maybe even for epileptic spasms associated to Down syndrome P38 -­‐ 1894 The development of a new Children’s Epilepsy Surgery Service (CESS) for England Christopher Verity, Cambridge, United Kingdom -­‐ [email protected] Objectives. To report on the development, the structure and the aims of the new CESS service for England. Materials and Methods. Recognising the need to improve the quality of children’s epilepsy surgery throughout England, the NHS National Specialised Commissioning Team invited children’s epilepsy centres to apply for a place in a new national Children’s Epilepsy Surgery Service. During November 2011 an Evaluation Panel that included international experts visited the centres that had applied to be part of the national network. Results. The panel recommended that there should be four centres in England and that the care of children undergoing epilepsy surgery should be concentrated in those centres. A National Clinical Co-­‐ordinating Group has been established, made up of representatives from each of the four centres, to ensure that the network provides a world class service. To facilitate consistent performance an on-­‐line database (based on International League Against Epilepsy criteria) has been developed to standardise the collection of data about clinical management and follow-­‐up. Difficult cases will be discussed between centres, working towards the development of a “national multidisciplinary team”. Conclusions. The aim is to improve quality by concentrating expertise and to increase the number of children who are assessed and treated. About 110 children a year currently have epilepsy 107 surgery in England. It is estimated that more than double this number would benefit from epilepsy surgery, so there are plans to increase capacity of the service. Advances in technology have enabled detailed non-­‐invasive assessments allowing many more children to be evaluated. The four CESS centres are eventually expected to see 1,050 referrals each year with about 350 selected for surgery. We aim to publicise the new CESS service because ongoing collaboration with centres around Europe will help to improve standards of care for children undergoing this complex surgery. P39 -­‐ 1891 Compare the value of ambulatory EEG (AE) and video telemetry (VT) in diagnosis and classification of seizures Iqbal M, Prasad M, Mordekar S, Kandler R. Sheffield Childrens Hospital, Sheffield, UK -­‐ [email protected] Objective: Compare the value of ambulatory EEG (AE) and video telemetry (VT) in diagnosis and classification of seizures Method: The EEG department database was interrogated retrospectively for children having both AE and VT recording during the period March 1998 to August 2011. Only patients referred for purposes of diagnosis of attacks and classification of epilepsy were included. Patients admitted for pre-­‐surgical evaluation of epilepsy were excluded. 48 patients were included in the study; M:F ratio 0.7:1, mean age 11.5 years, range 2 to 21 years. All patients had only 1 telemetry but 9 patients had more than 1 ambulatory recording. For the purposes of the study the result from the ambulatory recording preceding the video telemetry was used. Information regarding reason for referral and result of the long term EEG investigations was obtained Results: The reason for request was for diagnosis of attacks in 77% of AEs and 52% of VTs, classification of epilepsy in 16% of AEs and 43% of VTs. Recording length for AE was: 24 hours (68%) 48 hours (25%) and 72 hours (6%). Recording length for VT was 1-­‐3 days (60%) and 4-­‐5 days (40%). Typical attacks were recorded in 68% of AEs and 56% of VTs. The EEG helped in diagnosis in 66% of AEs and 62% of VTs. The EEG helped in classification in 21% of AEs and 56% of VTs. 62% of patients where AE was inconclusive (21% of the total) went on to have a VT. The combined yield of the investigations was 89%. Conclusion: AE is an effective tool for diagnosing seizures in two thirds of children. Where AE is inconclusive, VT improves the diagnosis in a further fifth. VT is superior to AE in classifying seizures. P40-­‐ 1882 What is the predominant feature of epilepsy in Down syndrome? Tarta-­‐Arsene O, Barca D, Iliescu C, Budisteanu M, Motoescu CH, Magureanu SA, Craiu DC. Pediatric Neurology Department, Clinical Hospital 'Al. Obregia", Bucharest, Romania -­‐ [email protected] Purpose: Down syndrome is a genetic disease due to an abnormality of chromosome 21, most frequent as trisomy related to mother’s age. In the definition of this disease, it was not describe as a specific trait epilepsy. This study will retrospectively analyze the features of epileptic seizures in children diagnosed with Down syndrome in a tertiary clinic from Romania, from a period of 5 years. Methods: retrospectively all files of children admitted for Down syndrome were analyzed and the patients who had epileptic seizures were included in the study. The clinical data (onset, types of seizures, clinical and mental exam, treatment, evolution) was analyzed and compared with lab tests (EEG and cerebral MRI) in order to find characteristic features of this association. The results were compared with published studies. Results: 9 patients (67% girls, 33% boys) with Down syndrome had different epileptic syndromes: 5 had infantile spasms, 3 focal seizures and one girl had only absences with eyelid myoclonia. The onset of seizures was below the age of one in 66% percent. The EEGs showed generalized discharges concordant to the epileptic seizures in 6 patients. 5 patients had complete control of seizures: 3 with infantile spasms with short time of corticotherapy, one girl with infantile spasms developed myoclonic astatic seizures and the patient with eyelid myoclonia with levetiracetam. One of the patients with infantile spasms evolved in Lennox-­‐Gastaut syndrome and died at the age of 6 due to a status epilepticus. All patients with focal seizures have a concordant structural lesion related to a vascular abnormality and have partial control with carbamazepine. Conclusions: Evolution of seizures in this genetic disease is dependent on existence of structural abnormality because only genetic traits are in general a good prognostic factor. P41-­‐ 1877 Low-­‐frequency repetitive transcranial magnetic stimulation (r-­‐TMS) treatment in children with refractory focal epilepsy; 2 case reports Thordstein M, Pegenius G, Andreasson A, Hallböök T. Departments of Clinical Neurophysiology, Gothenburg, Sweden -­‐ [email protected] Background: Over recent years, neuromodulation, with rTMS has been reported to be valuable for treatment of different conditions where the pathophysiologic background is believed to be a central nervous dysfunction. One such entity is epilepsy where positive effects have been reported in adults. In children, the experience is almost 108 non-­‐ existing. Given that the technique is non-­‐invasive and that there is no reason to believe that it could be harmful, it seems reasonable to try it at least in severe cases that do not respond to conventional therapy. Methods: Daily one hour sessions of low frequent repetitive TMS (rTMS, 0.5 Hz) were used to treat two children with severe epilepsy. A two year, eight months old boy has Alper’s disease and entered an epilepsia partialis continua with rhythmic jerking of the left upper extremity, mainly the hand. The seizures were pharmacoresistant and scalp-­‐ EEG could not reveal the seizure focus. The hand area of the primary motor cortex was localised using navigated TMS based on the patients structural MR. This position was used for rTMS treatment. A six year, three months old girl had a CSWS syndrome due to cortical malformations. After tapering of corticosteroids her seizure situation worsened. Scalp EEG revealed a number of seizure foci. While waiting for a planned neurosurgical treatment, rTMS was used directed by the EEG localisations. Results: The treatment sessions were mainly uneventful, in the majority the children slept during the stimulations. (The boy often needed a light procedural sedation though.) During two weeks of treatment, the number and severity of seizures reported by parents and personnel were reduced for both patients. Conclusions: rTMS can be performed successfully in small children. The procedure requires a lot of resources. If tried in less severe cases than the ones described, it may be even more efficient. P42 -­‐ 1873 Effect of anti epileptic therapy on serum homocysteine in children Kishore P, Pandey RR, Warsi S. Holy Family Hospital, New Delhi, India -­‐ [email protected] Background: Elevated plasma Homocysteine concentration is associated with increased risk for vaso-­‐occlusive disease like cerebrovascular stroke, coronary artery disease, and also the risk of resistance to anti-­‐epileptics and refractory epilepsy. Hyperhomocysteinemia has been frequently associated with the administration of Anti epileptic drugs (AED). This study aims at evaluating the effect of anti-­‐epileptic therapy on serum Homocysteine levels in children. Methods: 53 children(Males-­‐32,Females-­‐21) with Seizures in age group of 6 months-­‐ 14 years ,were recruited from the Pediatric Outpatient and Inpatient department of Holy Family Hospital, New Delhi were included in the study. Serum Homocysteine (Hcy)levels of Children already on AEDs for > 6 months(Group A) were compared with Children before Initiation of Anti epileptic drugs(Group B).These children were followed up after 6 months of Anti epileptic therapy and Serum Homocysteine was compared(Group C). Results: Average Hcy levels in subjects who had already received >6 months of antiepileptic drug therapy were 12.58±2.68 µmol/l, compared to 8.83±2.82 µmol/l, at recruitment (p=0.001). Significant increased levels were also observed in children followed up after 6 months of AED -­‐ 10.27 ± 3.06(µmol/l) compared to 8.63 ± 2.90(µmol/l) at initiation of AED. 9 children who received >1 AED had significantly higher levels-­‐14.15 ± 2.56 (µmol/l) compared to children on monotherapy-­‐10.22 ± 3.06(µmol/l). Carbamazepine therapy for 6 months caused significant increase in Hcy 10.78 ± 2.82(µmol/l) compared to baseline of 9.30 ± 2.70(µmol/l) (p=0.016) Conclusions: AEDs in children, particularly in those receiving multidrug or long duration treatment, cause hyperhomocysteinemia. This holds immense significance in malnourished populations. P43 -­‐ 1869 Effectiveness of corticosteroid therapy of intractable epilepsy in children depending on the initial changes in encephalogram Shalkevich Leonid. Belarussian medical academy of postgraduate education, Minsk, Belarus -­‐ [email protected] 74 children with pharmacoresistant epilepsy in the age of 6 months to 16 years were examined. In addition to anticonvulsant therapy the following corticosteroids were prescribed: prednisolone (N=31) and dexamethazone (N=43). Average daily dosage of dexamethazone made 0.42 + 0.3 mg/kg per day, that of prednisolone – 2.5 +/-­‐ 1.4 mg/kg per day. Initial EEGs were divided into 3 groups: those with registered epileptiform phenomena on normall background rhythm – 25.7% of patients, EEG with dominating of disorganized activity without epileptiform patterns – 43.2% of patients, with epileptiform activity on changed background – 31.1%. Maximum effectiveness of corticosteroid therapy was seen on EEG with disorganized activity without epileptiform changes. In this group it became possible to fully terminate seizures in 62.2% of patients, in 12.5% of children treatment was ineffective. Number of seizures declined by 25% in 9.3% of patients, by 50% -­‐ in 12.5%, by 75% -­‐ in 3.5%. Effectiveness of treatment in two other groups was essentially lower and results were alike: termination of seizures was noted in 31.6% of patients with isolated epileptic activity on EEG and in 34.8% of patients with combination of epileptiform activity and diffused disorganizing of background activity, the amount of seizures declined by 25% accordingly in 21% and 21.7% of patients, by 50% -­‐ in 21% and 17.4% of patients, by 75% -­‐ in 5.4% and 8.7%. Total absence of influence of CS upon course of disease was noted in 21% and 17.4% of them. Conclusion: received results of CS effect indicate at predominance of indirect anticonvulsant effect in their action 109 which determinates the main range of application – epilepsies connected with breach of brain bioelectrical activity maturation, and in lower measure – symptomatic forms of epilepsy with organizing of epileptic activity focus at the background of normally formed neurons. P44 -­‐ 1868 Clinical progress and prognosis of epilepsy in Tuberous Sclerosis Complex Djuric M, Kravljanac R, Tadic B, Peric M, Radojicic B. Mother and Child Health Care Institute of Serbia „Dr Vukan Cupic“, Belgrade, Serbia -­‐ [email protected] Purpose: More than 90% patients suffering from Tuberous Sclerosis Complex (TSC) have epilepsy, and in more than 60% of them it is the first presenting symptom. Seizures are often resistant to antiepileptic drugs and have a negative impact on the neurocognitive development. The aim of this study was to evaluate the clinical features and prognosis of epileptic seizures associated with TSC. Method: The medical records of 57 patients who satisfied the diagnostic criteria for TSC and were followed up for at least 2 years at the Neurologic Department of Mother and Child Health Care Institute of Serbia, between January 1988 and december 2012 were reviewed. Age of seizure onset, initial seizure type, clinical progress of seizures, efficacy of different treatment and psychologic development were evaluated. Results: From the 52 patients evaluated (5 had no seizuires) for seizures onset, it was in the first year of life in 85%. Seizures stopped in 41,6%. Occasional seizures and severe refractory epilepsy were seen in 58,4%. The most frequent type of seizures was partial. In the group with seizuire onset in the first year of life, there was a cessation of seizuires in 37,5%. and in patients with later onset in 42,8%. The difference was not statistically significant (p = 0.867). In the group with partial onset seizure they stopped less frequently than in spasm onset patients (10%: 33,3%) but the difference did not reach statistical significance (p=0,16).because of small sample. Conclusions: Epilepsy in TSC has a poor prognosis both in terms of chronicity and developmental outcome. In our group of patients type of initial seizuire and seizure onset time did not influence the prognosis. New insight in pathophysiology of TSC in recent years has led to clinical recommendations for treatment of epilepsy that may improve the outcome in these patients. P45 -­‐ 1854 Telangiectasias as a neurocutaneous feature Schieving JH, Willemsen MAAP, Seyger M, Weemaes C, Theelen T. Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Telangiectasias are prominent small vessels (venules, capillaries or arterioles) that are visible as small red-­‐purple focal lesions in the skin and mucous membranes. They can serve as a cutaneous marker for many different diseases, either primary (mostly hereditary) disorders like Hereditary Haemorrhagic Telangiectasia (HHT) and ataxia telangiectasia or secondary to other diseases like connective tissue disorders and cutaneous mastocytosis. Patients with telangiectasias are seen by general health practitioners, (pediatric) neurologists, dermatologists or ophthalmologists. In this presentation we give an overview of the different disorders in which telangiectasias are a prominent feature, focusing on neurocutaneous disorders in which they serve as a marker for establishing the right diagnosis. The pattern of distribution of the telangiectasias, their age of onset and associated features are helpful to distinguish between the different disorders. P46 -­‐ 1852 Parental experience and views about use of ketogenic diet in children and its impact on their quality of life Jayapal SSK, Mandava V, Jayawant S, Chandratre SR. Children’s Hospital, Oxford (CHOX), Oxford University Hospitals NHS Trust, Oxford, UK -­‐ [email protected] Objective: To obtain parents' and carers' views on their experience of ketogenic diet (KGD), impact on quality of life (QOL) of children and their views to improve services. Method: Parents of children who were on KGD from January 2008-­‐January 2012 were contacted by a single telephonic administrator for a survey using standard questions. Consistency was maintained in the tone and questions were read out following an introduction and parental consent. The responses were rated from 5 (strongly agree) to 1 (strongly disagree). Results: Parents of 11/15 children on KGD during the study period could be contacted and consented for a telephonic survey. 9/11 parents strongly agreed that the information regarding KGD and its side effects were adequately explained by doctors and dieticians and felt adequately supported by dieticians during KGD therapy. 8/11 strongly agreed that KGD was easy to initiate and maintain. 7/11 strongly agreed that KGD improved the QOL of children leading to a positive impact on the whole family. 6/11 strongly agreed (5/11 agreed) that KGD reduced seizure frequency and 9/11 reported reduction in emergency department attendances. Overall the experience with KGD treatment was positive in 10/ 11 families. Some parental comments regarding KGD were: ‘we wouldn’t survive without it’; ‘she was out of the wheel chair’ and ‘(KGD) just made our lives happier and easier’. Parents’ suggestions to improve 110 KGD services include need for offering motivation to families at the start of KGD, improved communication between dieticians and families and easy accessibility to local KGD services. Conclusion: Most parents perceived KGD as a positive experience decreasing seizure frequency and emergency department attendances and improving children’s quality of life. Adequate motivation prior to KGD commencement, improved dietetic support during KGD therapy and easy accessibility to KGD service may improve compliance with KGD therapy and parent satisfaction. P47 -­‐ 1794 Early predictors of long-­‐term cognitive, emotional and behavioural outcome in children with ESES: a retrospective study Weijenberg A, Vlaskamp DRM, Elting JW, Veenstra WS, Gutter T, Geerts Y, Brouwer OF, Callenbach PMC. Department of Neurology, University Medical Centre Groningen, The Netherlands -­‐ [email protected] Objectives: Long-­‐term outcome of Electrical Status Epilepticus during Sleep (ESES) is generally unfavourable but hard to predict in individual children. Longer duration of ESES and younger age at onset of ESES have been reported to be predictors of poor outcome, whereas any treatment response is associated with a relatively better prognosis. This study aimed at determining possible other early predictors of long-­‐ term outcome. Material and Methods: We retrospectively studied a cohort of 35 children with ESES, treated at the University Medical Centre Groningen (UMCG) and the Epilepsy Clinic of SEIN, Zwolle. We examined possible early predictors including duration between onset of clinical symptoms and definite diagnosis of ESES (diagnostic delay), and spike-­‐wave-­‐index (SWI). To evaluate long-­‐term outcome, school performance as well as cognitive, emotional and behavioural functioning was assessed with the parent-­‐ reported Brain Injury Alert -­‐ adapted for children with ESES. Results: Mean age at onset of epilepsy was 4.2 years; at onset of symptoms suggestive of ESES 6.5 years; and at diagnosis of ESES 7.6 years. SWI >85% was present in 40.0%, SWI 75-­‐85% in 34.3%, and SWI <75% in 25.7%. Parents of 23 children (response rate 65.7%) completed the questionnaire (66.7% focal seizures, 60.9% symptomatic epilepsy). Median diagnostic delay was significantly longer in children with a negative change of depressive feelings (16.0 vs 2.6 months, p=0.027) and in children with learning difficulties (11.8 vs 0.0 months, p=0.005). SWI >85% was overall associated with a less favourable outcome: categorized SWI differed significantly between children with and without a negative change in three parameters of the questionnaire: understanding language (p=0.013), depressive feelings (p=0.007), and indifference (p=0.049). Conclusions: In this retrospective study, both prolonged diagnostic delay and higher SWI are associated with unfavourable long-­‐term outcome and might therefore be early predictors for cognitive, emotional and behavioural outcome in children with ESES. P48 -­‐ 1793 Treatment of convulsive status epilepticus in the UMCG: a retrospective, observational study Vlaskamp DRM, Brouwer OF, Callenbach PMC. Department of Neurology, University Medical Centre Groningen, University of Groningen, The Netherlands -­‐ [email protected] Objectives: Little is known about clinical practice with respect to the application of guidelines in the treatment of Convulsive Status Epilepticus (CSE). This retrospective, observational study evaluated treatment of episodes of CSE in children at the University Medical Centre Groningen (UMCG). Material and methods: Episodes of CSE were derived from the UMCG database of children with epilepsy aged <18 years at time of their first (a)febrile seizure. Included for this study were episodes of CSE lasting ≥10 minutes, occurring between January 2000 and October 2012, in children aged >1 month. Treatments used in the UMCG were compared with recommendations from two most recent Dutch treatment guidelines for CSE in children aged >1 month. Results: 269 episodes of CSE occurring in 69 children (53.6% male, median age 4.3 years; range 0.1-­‐16.3 years) were included; 219 (81.4%) of the episodes started outside the hospital, 118 (43.9%) had remote symptomatic aetiology, 96 (35.7%) were accompanied by fever. Half of the CSE episodes lasted <30 minutes. Rectal diazepam was first treatment choice in first (58.9%; administered in ambulance in 46.6%) and subsequent episodes of CSE (43.3%; administered by parents at home in 55.1%). Intravenous clonazepam (and diazepam in first episodes of CSE) was preferred as second treatment choice; intravenous midazolam (and phenytoin as third choice in subsequent episodes of CSE) as third and fourth treatment choice. Individualized treatment protocols were associated with shorter total categorized duration of CSE episodes (p=0.002). In acute symptomatic CSE episodes, the sum of administrations of any therapy and the sum of different administered therapies were significantly higher compared to CSE episodes with other aetiology (p<0.05). Conclusion: Treatment of CSE episodes in the UMCG was overall in accordance with Dutch protocols and evidence-­‐based, except for the frequent use of intravenous clonazepam. Our study highlights the efficacy of individualized treatment protocols. P49 -­‐ 1792 Infantile spasms in the mother and daughter associated with 15q11.2q13.1 chromosome duplication 111 Riikonen R, Wallden T, Kokkonen H. Kuopio, Finland -­‐ [email protected] Objective: It is suggested that chromosomal microarray analysis (CMA) should be included in the diagnostic evaluation of patients with infantile spasms and developmental delay, when an evaluation for structural brain lesions and metabolic disorders reveal no abnormal findings. We add now a new genetic novel disease to the genetic list of infantile spasms. Material and Methods: We describe here infantile spasms in a mother and daughter. Both showed very similar clinical course: normal-­‐slightly subnormal early development, onset of infantile (flexor) spasms and typical hypsarrhythmia at age of 8-­‐ 9 months, good response to ACTH, and low normal cognitive development in the mother and but global delay in the child who has been exposed to valproate in utero. The cases were primarily considered to have cryptogenic aetiology. The mother developed epilepsy at age of 23 years with good control with valproate. Both had normal brain MRI. Results: Through etiological investigations did not reveal any aetiology. Chromosomal microarray analysis using HumanCytoSNP-­‐
12(v2.1) chip (Illumina) revealed the 6.2 Mb size 15q11.2q13.1 duplication inherited from the mother (arr 15q11.2q13.1 (22,754,322-­‐28,941,318)x3 mat, Hg19). The duplication was found in the daughter and also in the mother as well as in her autistic brother. Conclusions: This is the first report of maternal inheritance of 15 chromosome duplication (dup(15)(q11.2q13.1) in infantile spasms. The group of patients with cryptogenic aetiology will decrease when more careful chromosomal studies will be made. Our report is expanding the phenotype of chromosome 15q duplication syndrome. P50 -­‐ 1774 Respiratory and sleep disorders in female CDKL5 patients Hagebeuk EE, van den Bossche R, de Weerd AL. SEIN, Zwolle, The Netherlands -­‐ [email protected] Objective: In female children with drug-­‐resistant seizures and developmental delay from birth, atypical Rett syndrome caused bymutations in the CDKL5 gene should be considered. Several clinical features resemble classic Rett syndrome. Respiratory and sleep abnormalities are frequently present in Rett syndrome, whereas little is known in patients with CDKL5 mutations. Method: In four genetically confirmed female patients with CDKL5 mutations (age range 2–15y), the presence of breathing and sleep abnormalities was evaluated using the validated Sleep Disturbance Scale for Children and polysomnography (PSG). Results: The Sleep Disturbance Scale for Children indicated disorders of initiating and maintaining sleep, daytime somnolence, and sleep breathing disorders. In one patient, PSG showed central apnoeas during sleep: her total apnoea– hypopnoea index (AHI) was 4.9, of which the central AHI was 3.4 ⁄ h. When awake, central apnoeas were present in two of the four female children (central AHI 28 ⁄h and 41⁄ h respectively), all preceded by hyperventilation. PSG showed low rapid eye movement (REM) sleep (9.7–18.3%), frequent awakenings, and low sleep efficiency (range 59–78%). Conclusion: Episodic hyperventilation followed by central apnoeas was present while awake in two of four patients. This may indicate failure of brainstem respiratory centres. In addition, low REM sleep, frequent arousals (not caused by apnoeas ⁄ seizures), and low sleep efficiency were present. Similar to Rett syndrome, in patients with CDKL5 mutations PSG seems warranted to evaluate breathing and sleep disturbances. P51 -­‐ 1765 Safety and potential impact on growth and developmental skills of long-­‐term adjunctive zonisamide therapy in paediatric patients with partial epilepsy Guerrini R, Rosati A, Bradshaw K, Giorgi L. Neuroscience Department, Children’s Hospital Anna Meyer-­‐University of Florence, Florence, Italy -­‐ [email protected] Objectives: To assess long-­‐term safety of once-­‐daily adjunctive zonisamide therapy in paediatric patients with partial epilepsy, and its potential impact on growth and developmental skills. Materials and Methods: Patients (aged 6-­‐18 years) completing a Phase III placebo-­‐controlled trial entered a long-­‐term extension study, comprising a double-­‐blind transition period (patients previously treated with placebo were up-­‐titrated to a target zonisamide dose of 8 mg/kg/day; patients previously treated with zonisamide continued at same dose) followed by flexible, open-­‐label dosing (duration 45-­‐57 weeks). Safety assessments included treatment-­‐emergent adverse events (TEAEs), Tanner stages, skeletal development, Child Behaviour Checklist for Children Aged 6-­‐18 (CBCL 6/18), Physician and Parent/Guardian Global Impression of Change (GIC), and Controlled Oral Word Association Test (COWAT). Growth/development data are presented for changes from baseline of initial trial to Open-­‐Label Visit 5 (V5; Weeks 62-­‐71). Results: Of 144 patients entering study, 108 (75.0%) received zonisamide for >1 year. Most TEAEs were of mild or moderate intensity. Treatment-­‐related TEAEs were reported by 39/144 (27.1%) patients; most frequently, decreased weight (6.3%), decreased appetite (4.2%) and headache (2.1%). Rates of serious treatment-­‐related TEAEs and TEAEs leading to discontinuation were low (2.1% and 2.8%, respectively). Median (mean) changes from baseline to V5 were minimal for CBCL 6/18 Total Competence (-­‐1.0 [-­‐0.7]) and Total Problems (-­‐2.0 [-­‐3.0]) scores. Tanner staging and skeletal development were as expected for the study 112 population. Most patients were ‘Much improved’/‘Very much improved’ at V5 on both Physician GIC (73.8%) and Parent/Guardian GIC (75.5%). Median (mean) changes from baseline to V5 in COWAT Category Fluency and Letter Fluency scores were 2.0 (2.4) and 0.5 (0.4), respectively. Conclusions: Adjunctive zonisamide therapy displayed an acceptable safety profile with no consistent detrimental effects on growth and developmental skills when used to treat paediatric patients with partial epilepsy for >1 year. P52 -­‐ 1759 Clinical and Neurologic Outcomes of GEFS+ at Cheongju in South Korea Kim Won-­‐Seop , Sim Gi-­‐Youn. Chungbuk National University Hospital, Cheongju, Korea -­‐ [email protected] Purpose: Febrile convulsion is the most frequently diagnosed convulsive condition in infancy or childhood, with an incidence of about 2-­‐15%. In this study, we checked clinical feature and neurologic assessment of GEFS+ (Generalized Epilepsy with Febrile Seizure Plus). Methods: This study retrospectively examined clinical feature and neurologic assessment of GEFS+. We studied 24 GEFS+ children of Chungbuk National University hospital from January 2012 to December 2012. We formed them into two groups by age of first seizure; Group A(<6 years) and Group B(¡Ã6 years). We analyzed the clinical features, EEG findings and the neurological outcomes of the subjects. Result: The mean age of GEFS+ was 5.6 years. 11 subjects had their initial febrile seizures under 6 years of age while 13 subjects after 6 years of age. 5 Subjects had family history of seizure. The types of convulsions were mainly generalized. Eight (33.3%) showed abnormal finding on EEG and eight (33.3%) were treated with anti-­‐epileptic drug. The group with the initial seizures occurred under 6 years of age had more family of seizures, more developmental delay and was treated by antiepileptic drug. Conclusion: This study showed clinical feature and neurologic assessment of GEFS+. P53-­‐ 1757 Outcome of second-­‐line treatment with valproate or lamotrigine for absence seizure; On the condition that ethosuximide was temporarily unavailable in Korea Bin JH, Chung SY, Han JY, Eom TH, Kim SJ, Kim YH, Lee IG. Department of Pediatrics, College of Medicine, Catholic University of Korea, Incheon-­‐si, Korea -­‐ [email protected] Rationale: Ethosuximide (ESX), valproate (VPA) and lamotrigine(LTG) are used as first-­‐line treatment for absence seizure. Since the supply for ESX was discontinued due to its cost problems in 2010, treatment was no more to be extended. ESX monotherapy was replaced by VPA or LMT, and either excluding or switching ESX was done for patients who were originally treated with ESX combined with other anti-­‐ epileptic drug. Methods: A restrospective study was done for total 36 patients treated with ESX in 4 different hospitals associated with Catholic University of Korea between January of 2010 and December of 2012. Results: Among the total number of patients, 24 were treated with ESX monotherapy and 12 with ESX combined with other drug. In monotherapy group, each LTG and VPA was replaced for 12 and 4 patients respectively. Four patients finished treatment schedule, and total 3 patients were lost in the middle of study. Among 12 patients whose drug was switched to LTG, no seizure occurred in 5 patients, VPA was added to 4 patients and 3 patients switched again to another drug. In 4 patients VPA added, 3 had no problems and 1 had to replace VPA to LTG due to its side effect (weight gain). In combined therapy group, on the other hand, ESX was excluded for 11 patients while 1 switched to other drug. Among the 11 ESX-­‐excluded, 6 patients occurred no problems and 5 patients had to add ESX again. Conclusions: We were tried to analyze the treatment outcome for anti-­‐epileptic drug that was changed by external causes. LTG and VPA were chosen for the second-­‐line therapy instead of first. VPA had better outcome comparing to LTG, and LTG-­‐VPA combined therapy was more effective than LTG monotherapy. P54 -­‐ 1752 Prevalence of Idiopathic generalized epilepsy in children and adolescents -­‐ population based study Mazurkiewicz-­‐Beldzinska M, Steinborn B, Pilarska E, Szmuda M, Winczewska-­‐Wiktor A. Dept. of Developmental Neurology Medical University of Gdansk, Poland -­‐ [email protected] Purpose: Idiopathic generalized epilepsies (IGE) are generally viewed as having favorable outcomes, however the epidemiologic data concerning iIGEs is rather modest due to fact that most studies did not specifically analyze these syndromes. This study addresses the prevalence and clinical outcome in a well-­‐evaluated cohort of patients with IGE. Material and methods: All epilepsy patients who entered the Developmental Neurology Departments (In and Outpatients Clinics) during one year period were included in the study and followed prospectively. 1053 children and adolescents with diagnosed and treated epilepsy entered the study. We collected information on seizure freedom, EEG and MRI characteristics, medication use, demographic information and seizure history. Epilepsy syndromes included childhood absence epilepsy (CAE) juvenile myoclonic epilepsy (JME) IGE with only generalized tonic-­‐clonic (GTC) seizure, juvenile absence epilepsy (JAE), 113 epilepsy with myoclonic absences (MAE), and unclassified IGE. Results. IGE's among all epilepsy patients counted for 26 % of cases. There were majority of patients with CAE (38%), JME (37%), JAE (10%), MAE (6%), IGE with only generalized tonic-­‐clonic (GTC) seizure (4%) and 5% of unclassified IGE. Most of the patients (68%) were seizure free , 725 on monotherapy. The antiepileptic drugs which were used: valproate followed by lamotrigine, levetiracetam and ethosuxymide. Conclusions: IGEs constituted 26 % of cases in a largely cohort of pediatric epilepsy patients. Childhood Absence Epilepsy and Juvenile Myoclonic Epilepsy represents the majority of IGE cases. 68% of IGE achieved remission with AED therapy, mostly with a single drug. P55-­‐ 1743 The epilepsy phenotype in septo-­‐optic dysplasia (de morsier syndrome) Tarta-­‐Arsene O, Leanca M, Barca DG, Craiu D. Department of Pediatric Neurology, Clinical Hospital ''Al. Obregia'', Bucharest, Romania -­‐ [email protected] Purpose: Septo-­‐ optic dysplasia , also know as De Morsier syndrome is a rare congenital syndrome involving variable midline brain structures ,characterized by visual impairment, pituitary deficiencies, and specific brain abnormalities (absence of the septum pellucidum and corpus callosum). The phenotype is highly variable and the clinical presentation may be mild or extremely severe. Purpose of this paper is to present 2 clinical cases with epilepsy phenotype in Morsier syndrome. Methods and results: 2 girls diagnosed with Morsier syndrome have epilepsy syndrome. Clinical examination shows visual disturbances (nystagmus in both patients) and left ptosis in one girl, left hemiparesis in one girl, mild mental retardation in one girl and normal intelect in the other, left hypoacusis in one girl. They have all focal seizures, but one of them (the most affected one) has also generalized traits on EEG with photosensitivity. MRI shows optic nerve hypoplasia and hypoplasia of the corpus callosum and left renal agenesis. Antiepileptic treatment was started, but seizures are partial controled by treatment with decreased in frequency of seizures, but still EEG discharges. Conclusions: De Morsier syndrome is a rare syndrome associated with epilepsy and different clinical and EEG traits. P56 -­‐ 1738 Anti-­‐inflammatory treatment can reduce spontaneous recurrent seizure and depressive behavior in rats You SJ, Pineda E, Shin D, Mazarati A, Sankar R. Dept. of Pediatrics, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea -­‐ [email protected] Objectives: Recent experimental evidence and clinical observations suggest that the inflammatory process involved the pathogenesis of various neurologic diseases including epilepsy and its related morbidity and some kind of anti-­‐ inflammatory treatments can prevent inflammatory process in brain and reduce spontaneous recurrent seizures (SRS) and improve symptoms of epilepsy related depression and migraine. However, controversies are still remained. So, we assessed whether epileptic seizures and epilepsy-­‐related depression can be prevented or reduced by 2 weeks of treatment with the anti-­‐ inflammatory drugs (AIDs) CAY 10404, a COX-­‐2 inhibitor and recombinant IL-­‐ 1Ra in 34-­‐day-­‐old male Wistar rats with LiPC-­‐induced SE. Methods : The rats were divided into two groups, with one group injected with AIDs and the other control group injected with the same volumes of DMSO and saline, 1 hour before administration of pilocarpine. Results: The frequency of SRS was significantly lower in the AIDs treated than in the control group. Immobility time in force swim test was significantly lower in the AIDs treated than in the control animals. Timm staining was rarely observed in AIDs treated rats but was clearly discernible in the inner layer of rats in the control group. The mean gray value difference scores were significantly greater in the control than in the AIDs treated group. Conclusion: we found that the administration of a COX-­‐2 inhibitor and recombinant IL-­‐1Ra, starting before the induction of SE, attenuated the development of SRS and depressive behavior and inhibited mossy fiber sprouting in rats. P57 -­‐ 1731 A case of early onset epilepsy due to duplication of the sodium gene cluster on 2q24 with early seizure remission Gnidovec Strazisar B, Rener Primec Z, Writzl K. Department of Child, Adolescent and Developmental Neurology, University Children’s Hospital, Ljubljana, Slovenia -­‐ [email protected]­‐lj.si Objective: In contrast to point mutations and deletions, duplications of multiple sodium channel genes are less frequent cause of epileptic disorder. So far only nine patients with early onset epilepsy and 2q24 duplication involving the sodium channel gene cluster were described. They all presented with severe seizures that were refractory to antiepileptic treatment. We report another case of early onset epilepsy in association with 2q24 microduplication in whom seizure were well controlled in less than three-­‐week time. Case report: Patient presented with tonic seizures shortly after birth. Despite several seizures daily the episodes were firstly not recognized as convulsions. Her first EEG was performed at the age of 5 weeks and showed prominent slowing 114 and asymmetry of the background activity with multifocal epileptic discharges. The seizures were resistant to levetiracetam but with the introduction of topiramate and vigabatrine seizure remission was achieved in less than three weeks. Background EEG activity improved significantly with epileptiform discharges becoming less prominent and final disappearing. Despite that she experienced mild developmental delay. Extensive neurometabolic evaluation was normal and early MRI showed thinning of the corpus callosum. Subtelomeric FISH analysis showed a microduplication in the 2q24.2.2q24.3 region that was later confirmed with array comparative genomic hybridization revealing a 11.64-­‐Mb duplication of 2q24.2q31.1 region that included also a cluster of voltage-­‐gated sodium channel genes (SCN1A, SCN2A, SCN3A). Conclusion: Our case confirms that duplication involving the sodium channel gene cluster on 2q24 is associated with early onset epilepsy, which however may not be always very resistant since we were able to achieve early seizure remission despite late introduction of antiepileptic treatment. P58-­‐1716 Management of epilepsies combining antiepileptic drug therapy and various modalities of alternative therapies Smail Zubcevic, Amra Sabic. Paediatric Hospital, Clinical Centre, University of Sarajevo, Bosnia and Herzegovina -­‐ [email protected] Management of epilepsies combining antiepileptic drug (AED) therapy and various modalities of alternative therapies is still common, but scientifically ignored. The aim of this study (part of ongoing study on socioeconomic aspects of epilepsy) was to examine profile of parents applying such approach. Educational level, socioeconomic status, alternative treatments, factors involved in the formation of such a decision were investigated, and multivariate analyses were done. Compliance with AED regime was assessed by interview and measurement of AED serum concentrations where appropriate. 84 parents filled structured questionnaires in this part of study. 56% parents considered such management approach, only 27% actually applied it. There was one case where child promptly gained complete control of seizures with AED, in others epilepsy control was not gained in first 3 months. There was no significant difference of educational level. Slightly higher proportion of such practice was observed in rural areas, but the difference was not significant. Decision to try with alternative treatments was often result of multiple influences, mainly by friends and relatives (52%), and visiting internet portals (38%). Compliance with regime of AED therapy was in 70% of cases assessed as good. Most frequent modality of alternative treatments were various diets and vitamins, some form of exorcism and talismans (usually connected with visiting clergypersons of different denominations), herbal medicines. Satisfaction with simultaneous AED and alternative therapy was described as good in 26% cases, fair in 43% cases. Common explanation for starting such combined treatment was “it can not hurt” and fear of side-­‐effects of AED therapy was stated as a main reason in cases of poor compliance. We conclude that combination of AED and alternative treatment is quite common, in children of different socioeconomic and educational backgrounds, but sincerity of answers in questionnaires has to be scrutinized for better understanding of this problem. P59 -­‐ 1708 Parental education predicts IQ change after epilepsy surgery in children Meekes J, van Schooneveld M, Braams OB, Braun K, Jennekens-­‐Schinkel A, van Nieuwenhuizen O. University Medical Center Utrecht, The Netherlands -­‐ [email protected] Objective: To determine whether IQ change after epilepsy surgery in children is associated with environmental factors, specifically parental education (PE) or socio-­‐ economic status (SES). We focused on change (rather than pre-­‐ or post-­‐surgical IQ per se) because cognitive effects of surgery are increasingly considered in the decision to operate. Methods: Retrospective cohort study of children (< 18 years) who underwent epilepsy surgery between January 1996 and September 2010. Multiple regression analysis was used to identify predictors of change in IQ after surgery. To enhance interpretation of the results, we applied the same analysis to pre-­‐surgical and post-­‐
surgical IQ. Results: The sample included 118 children (median age at surgery 9.73 years [range 0.47 -­‐ 17.70 years]). IQ change after surgery was significantly predicted by a model only including PE. Although there was large variation between children with equal PE, the average difference between lowest and highest levels of PE amounted to 12.18 IQ points (95% CI: 1.20 -­‐ 23.16). SES was also significantly associated with IQ change after surgery, but inclusion of SES in the model already containing PE yielded no further contribution to prediction of IQ change. A model including age at surgery, duration of epilepsy, etiology, and type of surgery significantly predicted pre-­‐surgical IQ. The only significant predictors of post-­‐surgical IQ, however, were pre-­‐surgical IQ and PE, confirming the results concerning IQ change. Conclusions: For the first time, we demonstrate that, after paediatric epilepsy surgery, IQ increases most in children with highest PE or SES, whereas children with low PE or SES had smaller IQ increases or even decreases. Further study is required to determine whether this is due to 115 differences in medical management, pre-­‐existing disposition of the child or heterogeneity in post-­‐surgical environments. P60-­‐ 1698 Survey on infantile spasm management and treatment outcomes in a tertiary hospital in Hong Kong Maggie LY Yau, Karen KM Yam, Eva LW Fung. Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong -­‐ [email protected] Infantile spasm is usually refractory to conventional anti-­‐convulsants. This study aims to study the management of patients with infantile spasm, their outcome and possible contributing factors. Methods: All newly diagnosed patients with infantile spasm from June, 2006 till December 2012 in Price of Wales Hospital Hong Kong were reviewed. Their underlying etiology, choice of treatment and seizure outcome were studied. Results: Total 12 patients were diagnosed with infantile spasm. The age of diagnosis ranged from two months to three years old (median: seven months). Majority (67%) of patients have underlying primary neurological disorders. Two of them have delayed treatment (five and six months) due to parental concerns on possible significant side effects. For initial treatment choice, four chose prednisolone, while seven chose vigabatrin and one chose conventional anti-­‐
convulsants. No patient was required to discontinue treatment due to side effects experienced. Four patients have achieved remission after one month of treatment (One in steroid group and three in vigabatrin group). Three with refractory seizure required ACTH treatment (not readily available in Hong Kong) with good response, achieving seizure remission on day four and day nine of treatment. Depending on etiology, three in idiopathic group (75%) remained seizure free (ranging from seven months to 47 months; median 25 months). However in those with primary neurological disorder, four remained seizure free (50%) (ranging from 17 months to four years; median 17 months). One who was refractory to anti-­‐epileptic achieved remission after surgery was performed for removal of primary etiology. Conclusion: Idiopathic infantile spasm is a good prognostic indicator for outcome. In Hong Kong steroid phobia and ACTH availability remains an important issue towards the choice of treatment, which may have significant impact on seizure outcome. P61 -­‐ 1697 Postictal Psychosis: A rare entity in Childhood Epilepsy Iqbal M, Prasad M, Baxter P. Sheffield Childrens Hospital, Sheffield, UK -­‐ [email protected] Objective: To describe clinical presentation of Postictal Psychosis in a child who presented with a change in behaviour, hallucinations and confusion following cluster of seizures. Material ( case description): 15 years old boy, known epileptic on Levetiracetam, presented with hallucination and confusion after having cluster of seizures. Interestingly there was a clear history of him remaining well for nearly 24 hour followed by onset of hallucination where he was complaining of seeing “red blood on arm” and seeing flashing lights and at times shouting. On examination his GCS was 15/15, looked confused, not answering questions but following commands. Rest of neurological examination was unremarkable. Initial investigations including ammonia, CSF and blood lactate, CSF/plasma glucose ratio, plasma aminoacids were all normal. EEG didn’t show any epileptic discharges or evidence of subclinical status and background EEG showed rhythmic slow waves mostly in posterior region. Levetiracetam level came back as nearly 2 times the normal range. However he was on the same dose (2 gm) for nearly 3 months with no reported side effects. He remained in-­‐patient for 2 days; his psychotic symptoms slowly improved and didn’t need any specific treatment. His dose of Levetiracetam was subsequently reduced in view of the high levels. Result: Postictal psychosis is well known in adults but only sparsely reported in paediatric population. It usually occurs after prolonged partial complex seizure clusters with or without secondary generalisation. The psychosis commonly appears following a lucid interval, ranging from a few hours to days after seizure termination. Early recognition is important as suicidal tendencies have also been reported in adults. Discussion: We believe that the Paediatric Neurologist should be aware of this rare but distinct entity as early diagnosis helps in treating the patient effectively and alleviating patient and parents anxiety and also prevent unnecessary investigations. P62 -­‐ 1678 Benign convulsions with mild gastroenteritis in young children: a retrospective clinical study Kim DW, Kwon YS. Department of Pediatrics, Inje University Ilsan Paik Hospital, Goyang, Korea -­‐ [email protected] Objectives: The so-­‐called Benign convulsions with mild gastroenteritis (BCwMG), known as non-­‐febrile seizures associated with gastroenteritis without dehydration or electrolyte imbalance in young children aged almost 6 months to 3 years, has been reported relatively more frequently in the Far East. Because its seizures are non-­‐
febrile and can occur repeatedly, it can be misdiagnosed as epilepsy. Therefore, understanding of its clinical 116 characteristics is thought to be important. This study was carried out to investigate clinical features of BCwMG. Materials and Methods: From January, 2008 to December, 2012, thirty-­‐four patients with BCwMG were admitted at Department of Pediatrics, Inje University Ilsan Paik Hospital in Korea. We reviewed their medical records to investigate and analyze their clinical features. Results: Out of 34 patients with BCwMG, 26 were boys and 10 girls. Of 34 patients, 28 (82.4%) patients were between 1 and 2 years of age. Generalized seizure was observed in all 34 patients. The duration of seizure was between 10 seconds and 10 minutes. Mean seizure frequency was 1.9 times (range, 1-­‐5 times). Two or more seizures occurred in 20 patients (58.8%). All patients had seizures after the onset of gastroenteritis. All seizures occurred within the first 5 days of gastroenteritis. Rotavirus antigen was positive in stools in 16 out of 24 patients (66.7%). Conclusions: From our results, seizures in BCwMG were mostly brief and generalized and usually occurred as a cluster of episodes in young children aged 1 to 2 years. Seizures occurred within the first 5 days of gastroenteritis. The proportion of positive Rotavirus antigen was more than half. P63 -­‐ 1669 Rufinamide as adjunctive drug in refractory epilepsy due to neuronal migration disorders Coppola G, Moavero R, Cusmai R, Spalice A, Battaglia D, Verrotti A, Matricardi S, Pruna D, Parisi P, Curatolo P. Salerno University, Italy -­‐ [email protected] Objective. To evaluate the efficacy and tolerability of add-­‐on Rufinamide in children with refractory epilepsy symptomatic of neuronal migration disorders. Materials and Methods. We recruited 69 patients in a prospective, open-­‐label, add-­‐on treatment study from 8 Italian centers for pediatric and adolescent epilepsy care according to the following criteria: age 3 or above; focal or generalized seizures refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination, secondary to neuronal migration disorders; two or more seizures per month in the last 6 months; use of another AED, but no more than three, at baseline. Informed consent from parents and/or caregivers was obtained at the time of enrollment. Results. We enrolled 69 patients with a mean age of 15 years (range 3-­‐43). Forty-­‐three patients (62%) had a 50-­‐99% seizure reduction, and two (3%) became seizure-­‐free. Seizure frequency was unchanged in 18 (26%) and worsened in 6 (8.7%). Twenty-­‐nine patients (42%) reported adverse side effects, whilst taking rufinamide. Irritability was the most common side effect (11 patients), followed by decreased appetite (10), mood shift (6), vomiting (5), drowsiness (4), and decreased attention(2). Blood levels of concomitant anticonvulsive drugs were transiently abnormal in 5 patients. Conclusion. In our population of severely refractory epilepsy due to neuronal migration disorders, Rufinamide appeared to be effective and generally well tolerated. P64 -­‐ 1656 Clinical course and outcome of idiopathic childhood epilepsy: determinants of early and long-­‐term prognosis Dragoumi P, Tzetzi O, Vargiami E, Pavlou E, Krikonis K, Kontopoulos E, Zafeiriou D. 1st Department of Pediatrics, Aristotle University of Thessaloniki, Greece -­‐ [email protected] Objectives: To study the clinical course and outcome of idiopathic childhood epilepsy and identify variables determining both the early and long-­‐term prognosis. Methods: We followed 303 children with newly diagnosed idiopathic epilepsy both prospectively and retrospectively. Outcome was defined at one, 2 and 4 years of follow-­‐ up, as well as at the end of the study period for all patients. Based on the data collected, patients were classified in four patterns of clinical course: “excellent”, “improving”, “relapsing” and “poor”. Variables defined at intake and after the initial year of treatment were analyzed for their prognostic relevance towards the clinical course and outcome of the patients, using both univariate and mutivariate statistical analysis. Results: The mean age at seizure onset was 6,7 years and the mean duration of follow-­‐ up was 8,3 years (range 2,0-­‐22,0,SD 4,24). During the initial year of treatment, 70,3% of patients were seizure-­‐free. The course of epilepsy was “excellent” in 53,1% of the subjects, “improving” in 22,8%, “relapsing” in 22,1% whereas only 6 children with idiopathic epilepsy (2%) had a “poor” clinical course exhibiting drug-­‐resistance. Variables predictive of a poor initial response to therapy (p<0.05) were early seizure onset, multiple seizure types, history of febrile seizures, status epilepticus and sleep disorders. At the end of follow-­‐up, variables of predictive value were the presence of multiple seizure types and a history of migraine or sleep disorders. Conclusions: In the vast majority of children, the long-­‐term prognosis of idiopathic epilepsy is favorable. More than half of the patients attain seizure freedom immediately and their clinical course is considered “excellent”. About one fifth exhibit either an improving or a fluctuating course. Early seizure onset, multiple seizure types, history of febrile seizures, status epilepticus and sleep disorders are predictive of an initial poor response to treatment in children with idiopathic epilepsy. 117 P65 -­‐ 1653 Neurodiagnostic evaluations for differential diagnosis of syncope or epilepsy Min-­‐Jee Kim, Mi-­‐Sun Yum, Eun-­‐Hee Kim, Hae-­‐Won Choi, Tae-­‐Sung Ko. Division of Pediatric Neurology, Department of Pediatrics, Asan Medical Center Children's Hospital, Seoul, Korea -­‐ [email protected] Background: In children who visits outpatient clinic with history of loss of consciousness (LOC), the clinical diagnosis of seizure or syncope is always challenging issues to the pediatricians and child neurologists. We evaluated the differences between epilepsy and syncope in clinical features and laboratory tests to find a clue to help the diagnosis. Methods: We retrospectively reviewed the medical records of children who visited pediatric neurology in Asan Medical Center with history of LOC from 2007 to 2011. Patients with insufficient clinical history or laboratory data were excluded. Diagnosis of syncope or epilepsy was done in three different steps; clinical diagnosis by history taking, laboratory diagnosis depended on EEG and tilt test, and final diagnosis putting laboratory results, treatments and follow-­‐up episodes together. The clinical symptoms, result of EEG, EKG and tilt tests and prognosis of each final diagnosis were compared. The correlation between final diagnosis and clinical or laboratory diagnosis was also calculated. Results: Total 86 children (45 boys, mean age; 13.2 years) were reviewed. Seventy of 86 children (83%) were diagnosed as syncope, 8 (10%) syncope with epilepsy, 6 (7%) epilepsy, and 2 unclassified. Mean age at diagnosis, underlying disease, preceding symptoms, EKG and brain MRI findings were not significantly different among groups. Before diagnosis, the mean number of episodes was 3.2¡¾5 without significant difference between groups. During follow-­‐up periods after final diagnosis, the mean number of episodes were more frequent in epilepsy group (1.2¡¾3.8 vs 10¡¾10.3, p<0.001). The correlation coefficient of final and clinical diagnosis was higher than that of final and laboratory diagnosis (k=0.580 vs k=0.425, p=0.001). Conclusion: In this study, clinical history is more helpful than the laboratory data for the diagnosis of patients with LOC. However history taking and laboratory data are not definitive but important for the differential diagnosis of seizure or syncope. P66 -­‐ 1652 Benign familial neonatal seizures was confirmed through array CGH in Twins Kim SK, Lee JH. Hwa sung, Korea -­‐ [email protected] Introduction: Benign familial neonatal seizure (BFNS) is an autosomal dominant inherited form of epileptic syndromes in newborns It begins in the first few days of life and usually go away within 4 to 6 months. Mutations in two genes, KCNQ2 and KCNQ3 that are related to potassium channels, have been found to cause BFNS. The authors came across a case of BFNC in twins whose mutations of KCNQ2 genes were confirmed through array CGH. Case: Twin brothers were healthy boys without any medical findings, but they had been hospitalized in neonatal center after their birth. From the fourth day of life, more than 10 times asymmetric tonic seizures daily with apnea were observed in the twins. The blood gas analysis and blood tests including electrolyte and biochemistry tests during the seizures were all normal. The MRI result showed normal findings. A significant epileptiform discharges was not observed in EEG reading. The result of tandem mass screening, which could exclude any metabolic diseases, was also normal in both of them. The BFNS was suspected considering clinical findings, so array CGH was performed using twin¡¯ˉs peripheral blood. The result showed KCNQ2 gene partial deletion was confirmed on chromosome 20 and they were diagnosed as BFNS. Phenobarbital was injected intravenously on the first day from the seizure for both of them and changed to oral medication upon their discharge from the hospital, as there had been no seizure. Both have been observed through outpatient clinic without any medication so far. Conclusion: The authors report that the BFNS case in twins whose partial deletion in KCNQ2 gene on chromosome 20 was confirmed through array CGH. P67 -­‐ 1636 Generalized seizures in early childhood: clinical features and differential diagnosis Nechay A. Neurology department, Paediatric Hospital No1 of c.Kiev, Ukraine -­‐ [email protected] Objectives. Diagnosis and differential diagnosis of generalized seizures in early childhood is one of important task for paediatric neurologist. Hyperdiagnosis of epilepsy still happen in up to 30%. Materials and Methods. Retrospective study of medical notes of 142 children aged 1 month – 3 years hospitalized to tertiary medical institution for evaluation of generalized paroxysms suspicious for epilepsy during 2009 -­‐ 2011. Results. Generalized epileptic seizures were diagnosed in 73(51,4%), in 69(48,6%) – non –epileptic events. Generalized epileptic seizures mainly started during first 6m of life (56,2%); non-­‐epileptic events -­‐ mainly between 7 and 12m -­‐ 44,9%. 56(76,7%)children with generalized epileptic seizures had neurological deficit, whereas all but one with non-­‐epileptic events performed normal neurological examination. Frequency of events was statistically higher in children with epileptic seizures (>1 per day in 72,6%). Provoking factors were typical for non-­‐epileptic events 118 (94,2%), but also happen in children with epileptic seizures (12,3%). Family history was positive for same condition in 20,2% with non-­‐epileptic events and in 6,8% with epilepsy. 67(91,8%) children with epileptic seizures and 12 (17,4%) with non-­‐epileptic events had abnormal interictal EEG. Early debut and brain abnormality correlated with severer epilepsy. In 40 children specific electro-­‐clinical syndromes were diagnosed: in 33 (82,5%) – West syndrome, in 3(7,5%) -­‐ Othahara syndrome, in 2-­‐Lennox-­‐Gastaut syndrome in 1-­‐Doose syndrome, in 1-­‐
benign myoclonic epilepsy. Among non -­‐ epileptic events prolonged expiratory apnea was the most frequent condition (72,5%), reflex anoxic seizures were diagnosed in 20,3%, gratification – in 5,8%, Sandifer syndrome –in 2,9%, stereotypical behavior, benign myoclonus of sleep, benign tonic upgaze – in 1,4% each. Conclusions. Paroxysmal events suspicious for generalized epilepsy happen often in early childhood, leading to hospitalization, though many are of non-­‐epileptic origin. Careful anamnestic and clinical evaluation is essential for correct diagnosis especially in case of limited access to video-­‐EEG and its low efficacy in children with rare events. P68-­‐ 1631 Fine motor skills in children with benign rolandic epilepsy Ayaz M, Kara B, Soylu N, Ayaz AB. Sakarya Training and Research Hospital Child and Adolescent Psychiatry, Turkey -­‐ [email protected] Fine motor skills in children with benign rolandic epilepsy Abstract The aim of the present study was to evaluate fine motor skills in children with benign rolandic epilepsy (BRE) and healthy controls in order to investigate the relationship between fine motor skills, and seizure and treatment parameters in children with BRE. The study included 44 children aged ≥ 8 diagnosed as BRE and 44 age-­‐ gender-­‐, and level of education-­‐matched controls. Fine motor skills were evaluated using the Purdue Pegboard Test (PPT) and intelligence was measured using the Wechsler Intelligence Scale for Children (WISC-­‐R). All PPT subtest scores in the BRE group were lower than those in the control group. After performing covariance analysis to control for the effect of intelligence level (WISC-­‐R overall score) on motor skills, the difference between groups in PPT dominant hand, both hands, and assembly subtest scores persisted. Epileptic focus, treatment status, the type of antiepileptic treatment, age at the time of first seizure, time since the last seizure, and the number of seizures did not affect motor skills. In the present study, it was demonstrated that BRE was associated with impaired fine motor skills, independent of intelligence level, and the observed impairment was not associated with seizure parameters. Keywords: Child, benign rolandic epilepsy, fine motor skills. P69 -­‐ 1630 Efficacy of sublingual lorazepam versus intrarectal diazepam for prolonged convulsions in Sub-­‐Saharan Africa Kaputu KMC, Mukeba KD, Walker TD, Mukampunga C, Mafuta, Kokolomani J, Dubru J-­‐M, Mukendi KMR, Misson J-­‐P. Service of Child Neurology, Mons, Belgium -­‐ [email protected] Background: In Sub-­‐Saharan Africa, intrarectal diazepam (DZPIR) is the first-­‐line recommended anticonvulsant agent used in the emergency management of children with convulsions. We aimed to assess this standard care to sublingual lorazepam (LZPSL), a drug that is potentially as effective, safer, and easier to administer. Methods: A randomized controlled trial was conducted in the paediatric emergency departments of 5 hospitals in Rwanda and 4 in Democratic Republic of Congo. 436 children aged between 5 months and 10 years with convulsions persisting for more than 5 minutes were randomly assigned to receive DZPIR (0.5mg/kg, n=202) or LZPSL (0.1 mg/kg, n=234). The primary outcome was cessation of convulsions within 10 minutes of administration of a single dose of the assigned medication. Results: LZPSL stopped convulsions in 56.0% (131/234) of children treated and DZPIR in 79.2% (160/202; p ˂0.001). The administration of LZPSL significantly increased the probability of treatment failure (OR=2.95, 95% CI 1.91-­‐4.55). There was no statistically significant difference as far as 24 hour seizure recurrence and 24 hour mortality (p=0, 48 and p=0, 13 respectively) were concerned. Conclusion: LZPSL was less effective than DZPIR in terminating seizures within ten minutes of drug administration in this cohort of children with prolonged seizures. The ease of use of LZPSL still makes it an attractive treatment option where DZPIR is not rapidly available. P70 -­‐ 1625 Vitamin B12, Folic Acid and Homocysteine Levels in Children with Febrile Seizure Ozkale Y, Erol I, Saygi S, Kýlýçaslan B, Ozkale M, Sariturk C. Baskent University Faculty of Medicine, Department of Pediatrics, Adana Teaching and Medical Research Center, Adana, Turkey -­‐ [email protected] Objectives: Although febrile seizure is the most common brain-­‐related disease in children, its pathophysiology is still unknown. Several studies have indicated that multiple factors can be involved in the pathogenesis of febrile seizure. This study was designed to address whether vitamin B12, folic acid and homocysteine have any role in developing febrile seizure. Materials and Methods: This prospective study enrolled 104 children who presented 119 with febrile seizures and 73 children who presented with a febrile illness without seizures between October 2012 and March 2013. The serum levels of vitamin B12, folic acid and homocysteine were measured both from the febrile seizure and control groups. Results: The present study indicate that, the serum vitamin B12 levels of children with febrile seizure were significantly lower than that of febrile children without seizure. There was no significant difference in folic acid and homocysteine between the febrile seizure and control groups. On the other hand folic acid was significantly lower in the febrile seizure group who had more than three convulsion and who had a body temperature under 39 °C during convulsion. Conclusions: These data indicate that low body vitamin B12 levels may decrease the threshold of seizure and be a risk factor for the development of febrile seizures. In addition low folic acid levels appear to be associated with an increased risk of recurrence in febrile seizures. P71 -­‐ 1624 Attention deficit and the Associated Clinical Factors in Children with Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS) Eun-­‐Hee Kim, Mi-­‐Sun Yum, Hyo-­‐Won Kim, Tae-­‐Sung Ko. Division of Pediatric Neurology, Department of Pediatrics, Asan Medical Center Children's Hospital, Seoul, Korea -­‐ [email protected] Objectives: Children with epilepsy often experience attentional problems with less favorable outcomes. We assessed the attention in benign childhood epilepsy with centro-­‐temporal spikes (BCECTS) and tried to identify the associated seizure variables which cause attentional problems. Materials and Methods: A total of 266 children were diagnosed with BCECTS at Asan Medical Center from 2004 to 2012. Among them, 93 children (57 males) who performed the formal attention test (ATA or CAT) were retrospectively reviewed. Clinical data including sex, age of seizure onset, seizure control, EEG findings, and response to treatment were analyzed to evaluate the association with attention deficit. Results: A mean age of seizure onset was 7.5 (3.3~13.3) years and mean follow-­‐up duration after diagnosis was 3.4 (1~8.7) years. Of 93 patients, 63 (67.7%) were diagnosed as having attention deficit, including the inattentive type (32 cases, 50.8%) and the combined type (25 cases, 39.7%). The incidence of attention deficit was significantly higher in children with a younger age of seizure onset (86.5% [3-­‐6 years]vs 55.4% [7-­‐14 years], p=0.02). However, other clinical factors, frequency and laterality of spike discharges on electroencephalogram (EEG), duration of treatment, seizure control were not associated with the incidence of attention deficit. And there was no factor related to attention quotient of visual or auditory selection. Eighteen patients (28.5%) were treated with central nervous system stimulants, and their epilepsy related factors and outcome were similar with those of patients without stimulant medication. There was no case with aggravated seizure after stimulants Conclusions: Children with BCECTS have a high incidence of attention deficit and early onset of seizure was associated with this attention deficit. Therefore, systematic screening and proper management for attentional problems should be carried out in these patients. P72 -­‐ 1622 Clinical experience of lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy Jon Soo Kim, Ho Jin Park, Hunmin Kim, Byung Chan Lim, Jong-­‐Hee Chae, Jieun Choi, Yong Seung Hwang, Ki Joong Kim, Hee Hwang, Hye Won Ryu. Department of Pediatrics, Eulji University Hospital, Daejeon, Republic of Korea -­‐ [email protected] Purpose: To evaluate the efficacy and safety of lacosamide in pediatric patients with refractory focal epilepsy. Methods: We retrospectively reviewed the medical records of children younger than 18 years of age with oral lacosamide as an adjunctive treatment for refractory focal epilepsy at the Seoul National University Bundang Hospital. Clinical information regarding the characteristics of patient¡¯ˉs epilepsy and outcome of lacosamide treatment was gathered and analyzed. Results: Twenty-­‐two patients (17 boys and 5 girls) were included in the study, a mean age of 12.9 (range, 1.2 -­‐ 18.9 years). The mean number of concomitant AEDs was 3.0 (range, 1 -­‐ 6) and mean duration of follow-­‐up was 10.1 months (range, 6.1 -­‐ 13.0 months). The mean maintenance dose was 5.4 mg/kg/day (range, 1.4 -­‐ 9.8 mg/kg/day). Fourteen patients (64%) were responder, four of these patients were seizure free at the latest follow-­‐up. Six patients (27%) were non-­‐responder: two of these presented with < 50% seizure reduction and six had no change in seizure frequency. Two others (9%) discontinued the oral lacosamide because of adverse events (aggressive behavior and depression). Mild transient treatment-­‐related adverse events were observed in 8 of the 22 patients (36%). Conclusions: Lacosamide represented a useful drug that is effective for a wide range of pediatric refractory focal epilepsy and was well tolerated. P73 -­‐ 1621 Frequency of prenatal and neonatal complications in children with epilepsy in a tropical country Dalbem JS, Siqueira HH, Alvarenga RP. Federal University of Mato Grosso and Federal University of State Rio de Janeiro, Brazil -­‐ [email protected] 120 Background: Epilepsy affects approximately 50 million individuals around the world, 90% of whom live in developing countries. It is estimated that 2.4 million new cases occur each year worldwide, with around 50% of these cases occurring in childhood and adolescence. Objective: Determine the frequency of prenatal and neonatal complications in a sample of children with epilepsy in a small town of Brazil. Methods: A cross sectional study was conducted in the mid-­‐northern area of Mato Grosso, Brazil, in children of 0-­‐14 years of age who had been diagnosed with epilepsy during 2010. Results: Sixty-­‐five children with a diagnosis of epilepsy were evaluated, 53.8% males. The average age was 6.98 years. About 88% of whom lived in an urban area. In 73.9% of the patients, the first epileptic seizure occurred within the first two years of life. In the prenatal and neonatal periods, 40% of the children had suffered complications such as hypoxia and epileptic seizures. Regarding the sex of the child, found a lower prevalence of complications in male children, this being statistically significant association (PR= 0.51, CI95% =0,29-­‐0,96). Observed that lower maternal education and family income, the higher the frequency of neonatal complications (PR=0,60; CI95% =0,33-­‐1,08 and PR=0,45; CI95% =0,26-­‐0,78). Founded 2.34 times more the occurrence of neonatal complications among children with low birth weight (IC95% = 1,43-­‐ 3,84). There were 1.51 times more occurrence of neonatal complications among children who were born at cesarean section, although not statistically significant. Conclusion: In developing countries improve in primary healthcare, including high quality prenatal care, care for the pregnant woman during delivery, and care and follow-­‐up for the newborn infant may reduce structural and metabolic abnormalities and therefore the number of cases of epilepsy. P74-­‐ 1619 Clinical characteristics of gastroenteritis associated afebrile seizure in a tertiary hospital in Hong Kong Kwan-­‐Ming Yam, Lo-­‐Yee Yau, Eva Lai-­‐Wah Fung. Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong -­‐ [email protected] Objective: To study the clinical characteristics of gastroenteritis associated afebrile convulsions in Hong Kong. Method: Medical records of healthy children who suffered from acute gastroenteritis with afebrile seizure from January 2011 to December 2012 in Prince Of Wales Hospital in Hong Kong were reviewed. Their demographic data, clinical features, pathogen identification and neurological outcome were studied. Results: Nineteen children with normal premorbid status suffering from gastroenteritis with afebrile convulsion were identified, including 9 males (47%) and 10 females (53%). Age ranged from 13 months to 12 years old (Median=18 months). All children enjoyed good past health except one had history of febrile convulsion. 14 (74%) were affected during summer months (June to September) with clustering of 7 cases (36%) in August 2012. All had satisfactory hydration except one with mild dehydration. Seizure occurred on day 2 to 5 of illness with 12 children (63%) having generalized tonic-­‐clonic seizure and 7 (37%) having tonic seizure. 11 children had seizure recurrence, ranging from 1 to 4 times. They recurred within first 24 hours except 1 child had an attack 3 days later. The duration of seizure ranged from 10 seconds to 15 minutes (median=3 minutes). All children had serum electrolytes checked and only 2 had hyponatraemia down to 118mmol/L and 132mmol/L respectively. 17 children (89%) had stool results available with Norwalk virus isolated in 11 children (65%) and Rotavirus in 2 children (12%). 15 had neuroimaging, 6 had cerebrospinal fluid assay and 13 had electroencephalogram recording, which were all normal. All children did not require long term anti-­‐epileptic treatment and had no subsequent admission for convulsion. Conclusion: Afebrile seizures associated with gastroenteritis are relatively common in Hong Kong. It comes in clusters and is mostly associated with Norwalk virus infection. The neurological outcome at discharge is generally favorable. But long-­‐term follow up studies may help to clarify the outcome, especially in cases with prolonged seizures. P75 -­‐ 1611 Midazolam oromucosal solution versus rectal diazepam for prolonged acute convulsive epileptic seizures: Italian cost-­‐effectiveness analysis Lee D, Anelli M, Gladwell D, Saunders A. BresMed, Sheffield, UK -­‐ [email protected] Objectives: Current care in Italy for first-­‐line treatment of seizures in the community is rectal diazepam, but carers are reluctant to use this due to patient dignity and social acceptability issues. BUCCOLAM® (midazolam oromucosal solution) is indicated for the treatment of prolonged, acute, convulsive seizures (PACS) in children and may be used by parents and other carers in a community setting where a child has been diagnosed with epilepsy. A decision-­‐tree model was developed to assess the cost-­‐ effectiveness of BUCCOLAM compared to rectal diazepam for the treatment of PACS occurring in the community. Materials and Methods: The model allows different treatment options, including whether or not (1) a carer administers treatment, (2) an ambulance is required and patients are taken to hospital, and (3) inpatient stay is required. The primary outcomes are the cost impact of PACS, including emergency care and hospitalisation costs, and health-­‐related quality of life. 121 Efficacy and effectiveness data were obtained from McIntyre et al (2005) and a Delphi panel. Costs were taken from Italian national databases. The price of BUCCOLAM was taken from the Gazzetta Ufficiale. Rectal diazepam is not reimbursable therefore its cost is not included. Results: Clinicians estimated that compared to rectal diazepam BUCCOLAM would increase the likelihood of successful treatment, and therefore reduce ambulance call-­‐outs and hospital stays. It is predicted to save €1,540 per patient and improve quality-­‐adjusted life years by 0.003 over 1 year. At an uptake of 10% of eligible patients this would deliver cost savings of €8-­‐17 million over 1 year. Conclusions: Treatment with BUCCOLAM reduces the requirement for emergency and hospital care and is cost saving compared to rectal diazepam. More patients are successfully treated at seizure onset in the community due to reduced concerns surrounding patient dignity and an easier administration route. P76 -­‐ 1607 Guidelines on the management of prolonged acute convulsive seizures in out-­‐of-­‐hospital settings: a gap to be filled Lagae L, Arzimanoglou A, Beghi E, Bennett C, Cross HJ, Mifsud J, Schmidt D, Wait S, Harvey G. KULeuven, Neuro-­‐
musculo-­‐skeletal Research Unit, Leuven, Belgium -­‐ [email protected] Objectives: Prolonged acute convulsive seizures require immediate treatment with benzodiazepines in order to prevent their progression to status epilepticus. Most seizures occur outside of the hospital, thus practical guidance is needed for non-­‐medically trained caregivers who wish to administer rescue medication in out-­‐of-­‐
hospital settings. The purpose of this paper is to determine whether existing clinical guidelines on the management of prolonged acute convulsive seizures in children contain such guidance. Materials and methods: As part of the Practices in Emergency and Rescue medication For Epilepsy managed with Community administered Therapy (PERFECT) initiative, a pragmatic review of the published literature and of professional society websites was undertaken to identify national relevant clinical guidelines in France, Italy, Germany, Spain, Sweden, and the United Kingdom. All searches were conducted in English and local languages. Results: Most existing guidelines focus on the hospital setting. Only the UK guidelines specify that all non-­‐medically trained caregivers should receive dedicated training and that all children with a history of prolonged seizures should have an individualised healthcare plan. All guidelines recommend treatment of prolonged seizures after 5 minutes with either rectal diazepam or buccal midazolam, depending on availability of these medicines and, in some countries, on patient preferences. Different specialties (neurology, paediatric neurology, intensive care medicine) were involved in drafting guidelines depending on the country. Conclusions: Most existing guidelines do not provide practical recommendations to caregivers in out-­‐of-­‐hospital settings on the administration of rescue medication. Filling this gap is critical to ensure that children at risk of prolonged acute convulsive seizures receive their rescue medication quickly and safely regardless of where their seizure occurs, thereby avoiding unnecessary treatment delays, clinical sequelae and costly admission to hospital. P77 -­‐ 1597 Clinical spectrum and treatment outcome of children with West Syndrome in children from Northern India Kaushik JS, Patra B, Sharma S, Aneja S. Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children Hospital, New Delhi, India -­‐ [email protected] Objective: This study was intended to document the clinical profile and treatment outcome of West syndrome in children attending a tertiary care center in Northern India. Material and Methods: Data were collected by a retrospective chart review of children admitted with a diagnosis of West syndrome between January 2008 and January 2012. Information was recorded pertaining to clinical profile, age at onset and presentation, etiology, and associated co-­‐morbidities; result of electroencephalography (EEG) and neuroimaging; treatment given; and final outcome. The following drugs were used to control spasms: pyridoxine, prednisolone, vigabatrin, sodium valproate, nitrazepam, topiramate, and levetiracetam. The response to drugs was categorized as spasm cessation, partial improvement (>50% improvement), or no improvement. The final outcome was considered favorable when there was a complete cessation of spasms; with absence of relapse and no progression to other seizure types for at least subsequent 6 months. Results: Records of 148 children (120 boys) were retrieved and analyzed. The mean (SD) age at onset and presentation was 5.3 (4.6) months, and 13.1 (7.3) months, respectively. The majority of the children had delayed development (92.5%). Perinatal asphyxia (61.4%), neonatal sepsis/meningitis (10.6%), and postnatal meningitis (11.4%) were the predominant causes. The etiology could not be ascertained in 16.6% of children. Favorable outcome was observed in 45 (30.4%) children with spasm cessation rate of 25.4% with prednisolone. Age at onset, gender, time lag to treatment, presence of perinatal asphyxia, or comorbid cerebral palsy did not affect the final outcome. Conclusion: This study highlights the developing country perspective of children with West syndrome, including delayed presentation, adverse perinatal events as the predominant etiology, and modest response to oral steroids. 122 P78 -­‐ 1596 The cost effectiveness of midazolam oromucosal solution for the treatment of prolonged acute convulsive epileptic seizures in France Lee D, Porter J, Tate E, Saunders A. BresMed, Sheffield, UK -­‐ [email protected] Objectives: BUCCOLAM® (midazolam oromucosal solution) is indicated for the treatment of prolonged acute convulsive seizures (PACS) in children. A cost–utility model demonstrates the incremental value of BUCCOLAM compared to current treatments administered in the community setting for children with epilepsy in France. Materials and Methods: Clinical events following seizure onset were simulated using a decision-­‐tree model. The primary outcomes are the cost impact of PACS, including expected ambulance call-­‐outs, emergency hospital visits and inpatient hospitalisation, and health-­‐related quality of life (HRQL). Efficacy data were obtained from a published study of 177 children suffering 219 separate seizure episodes. A Delphi survey of French clinical experts provided estimates of how choice of rescue medication influences events in the community setting. Resource use costs were obtained from the National Security Agency of Medicines and Health Products and French social security databases. Results: Clinician responses defined current care as rectal diazepam (92%) and clonazepam (8%) and estimated that treatment with BUCCOLAM would result in an increased chance of successful treatment in the community setting compared to current care, reducing the requirement for emergency services and hospital resource use. Compared to current care, BUCCOLAM showed a cost saving of €2,637 and an increase in HRQL by 0.0002 quality-­‐adjusted life years over 1 year. Similar savings were expected compared to rectal diazepam alone. Conclusions: Treatment with BUCCOLAM reduces the requirement for emergency and hospital care and is cost saving compared to current medications. More patients are successfully treated at seizure onset due to: • Fewer dignity concerns and an easier administration route compared to rectal preparations • Licence wording that specifically allows caregivers and teachers to administer treatment; previously they may not have felt able to do so or were not permitted to • Improved or equal efficacy in stopping seizures and preventing recurrent seizures. P79 -­‐ 1579 Role of EEG in diagnostic of focal epilepsy Kušar M, Kirevski M. Ljubljana, Slovenia -­‐ [email protected] Plenary session for Pediatric European society for nurses and technician. Aim: Up to 60 % of patients with focal epilepsy may manifest pharmacoresistance and more than half of them may be candidates for epilepsy surgery. Goal of resective surgery aims at the complete resection of epileptogenic zone while sparing eloquent cortex. Epileptogenic zone is the cortical area responsible for generating epileptic seizures. The neurophysiology assistant should have enough knowledge and experience and above all must be able to identify and recognize all abnormalities of brain electrical activity, observe patient clinical manifestation and perform age appropriate testing of patient during the seizures. For this presentation we reviewed focal epileptic discharges in EEG recordings of paediatric patients who underwent resective surgery. Methods and patients By assessing ictal and interictal EEG, as well as ictal semiology the neurophysiology assistant can help to predict possible epileptogenic zone. Careful analysis of patient's symptoms and signs during seizure allows neurophysiology assistant to estimate the putative symptomatogenic zone. With scalp EEG he can record interictal and ictal epileptiform discharges that gives us information of epileptogenic zone, but if epileptogenic focus is restricted, obscured or inaccessible to recording scalp electrodes, we can use additional scalp electrodes and/or invasive recording is required. Some examples of different types of ictal and interictal EEG patterns in focal epilepsies in children will be presented. All EEG studies were recorded in patients who were referred from Ljubljana, Department of Child, Adolescent and Developmental Neurology, for resective surgery to major epilepsy centers in Europe. Conclusions Diagnosing of focal epilepsy in children is challenging because of EEG maturation and also because of occurrence of specific focal epileptic patterns during different paediatric periods. From our review of cases we aim to present all the complexity of various patterns of focal epilepsy in different age group. P80-­‐ 1574 Dyskinesia as a new adverse effect of hormonal treatment in West syndrome Sukhudyan B, Dimova P, Vigevano F. ”Arabkir” Medical Complex and Institute for Child and Adolescent Health, Yerevan, Armenia -­‐ [email protected] Objectives: West syndrome is an age-­‐dependent epileptic encephalopathy. Besides its potential harm, hormonal therapy remains main treatment in West syndrome. Here we report on 9 patients with appearance of unusual mostly hyperkinetic movements on treatment. Materials and methods: In this retrospective observational study we looked at patients who developed unusual movements during steroid therapy for West syndrome. Inclusion 123 criteria were infants with spasms, hypsarrhythmia in EEG and occurrence of hyperkinetic movements on hormonal therapy. Results: Facial grimacing, repetitive mouth opening, adduction and abduction of upper and lower extremities and periodical strabismus in different combinations were observed in all patients independently on formulation, dose, duration and efficacy of treatment. They disappeared in sleep and reappeared immediately on arousal. They interfered with feeding and emotional smile; involuntary eye muscle movements made an impression of absent visual fixation. However, tube feeding was never required. Hyperkinesis in extremities interfered with voluntary movements. Dyskinesias stopped gradually in a month after discontinuation of treatment. Repeated EEGs did not show correspondent epileptiform activity. In 3 patients, besides dyskinetic movements we observed sustained retro-­‐ and torticollis. In all cases we registered disappearance of hypsarrhythmia, although control of spasms was not always satisfactory. A specific cause of West syndrome was identified in only 4 patients. Genetic testing in one and medical history (severe birth asphyxia) and clinical data (microcephaly, spastic tetraparesis) in another helped to establish genetic and structural causes of West syndrome, respectively. A structural origin of West syndrome was proved by brain MRI investigations in 2 patients with multiple focal dysplasias and severe brain atrophy of unknown origin, respectively. Conclusion: We conclude these abnormal movements can be attributed to side effect of hormonal treatment. P81 -­‐ 1571 Intravenous levetiracetam for continuous spike and wave during slow sleep Shinhye K. Myongji Hospital, Goyang, Korea -­‐ [email protected] A 6-­‐year-­‐old girl visited the pediatric clinic for hematemesis during sleeping. She had been grown up without significant health problems until she was rescued from drowning in swimming pool two weeks before having seizure. She was performed cardiopulmonary resuscitation for 7 minutes immediately after noticed by lifeguard. On brain MRI after treated for aspiration pneumonia, no abnormal signals were seen. On neurologic examination, abnormal focal neurologic signs were not shown. Her mother reported her hematemesis with decreased responsiveness during sleeping, only two weeks later, when she visited my clinic second time. On electroencephalography, nearly consistent spike and wave discharges was seen during sleeping, her mental status was stuporus, that we urgently started intravenous levetiracetam, 20mg/kg and maintained it with 20mg/kg/day and titrated with 10mg/kg/day until 40mg/kg/day. After two days of intensive care, epileptiform discharges disappeared and she could communicate fluently and was improved to alert mental status. On the second brain MRI on recovering state, abnormal signals were not found on T1, T2 and FLAIR images, either. Conclusion: Levetiracetam can be effective treatment option in children for continuous spike and wave discharges during slow sleep as we described. P82 -­‐ 1567 The efficacy and safety of levetiracetam in pediatric patients treated with chemotherapeutic agents for hematologic disorders Bayram E, Topcu Y, Tufekci O, Karaoglu P, Yis U, Oren H, Hiz SK. Dokuz Eylul University Hospital, Division of pediatric neurology, Izmir, Turkey -­‐ [email protected] Purpose: We aimed to describe the efficacy and safety of levetiracetam in pediatric patients receiving chemotherapy for hematologic disorders. Material methods: Children with hematologic disorders who were receiving chemotherapy agents and developed seizure during treatment and treated with levetiracetam were included in the study. The clinical data of the patients were retrospectively evaluated. Primary hematologic diagnosis, chemotherapeutic agents, age at first seizure, seizure type, interictal electroencephalography findings, magnetic resonance imaging findings, response to the levetiracetam treatment, dose of levetirasetam, levetiracetam side effects and treatment period were recorded. Results: Ten patients with a mean age 12.4±2.96 years were included in the study. Possible triggering factors for seizures were chemotherapeutic agents in 60 % (n=6), posterior reversible encephalopathy syndrome in 20 % (n=2) and central nervous system involvement of the primary disease in 20 % (n=2). Nine patients received levetiracetam monotherapy and one patient received levetiracetam that was added on oxcarbazepine due to the intractable seizures. The mean duration of antiepileptic treatment that overlapped with chemotherapy was 7.3 ±3.5 months. Nine patients (90 %) were seizure free after levetiracetam monotherapy and one patient (10 %) had ≥ 50 % seizure reduction after levetiracetam who was previously treated with oxcarbazepine. No side effects were observed for levetiracetam during treatment. Conclusion: Levetiracetam treatment is safe and effective to prevent seizures in children receiving chemotherapy for hematologic disorders. 124 P83 -­‐ 1562 Epilepsy and autoimmunitiy in pediatric patients Bektaþ Ö, Jacobson L, Tutkak H, Karagöl S, Lang B, Clover L, Vincent A, Deda G. Department of Pediatric Neurology, Ankara University Medical School, Ankara, Turkey -­‐ [email protected] Aim: Anti-­‐epileptic drugs are used as the main treatment of epilepsy. However, one-­‐ third of epilepsy patients do not respond to antiepileptic drugs. In addition, a large portion of epilepsy etiology is still unknown. Our aim was determine the role of the autoantibody, and autoimmunity in epileptic patients with undetermined etiology. Materials and Methods: One hundred subjects (80 patients, 20 healthy controls), who were referred to the Pediatric Neurology Department at Ankara University between November 2011 and April 2012, were enrolled in the study. ANA, anticardiolipin IgG, antiphospholipid, anti-­‐thyroid peroxidase, anti-­‐paraneoplastic antibodies(Hu, Ma2, CV2/CRMP5, Yo, Ri ve ampicilin), GAD, and anti-­‐N-­‐methyl-­‐D-­‐aspartate receptor antibodies were studied in our university laboratory. Additionaly anti-­‐NMDA and voltage-­‐ gated potassium channel-­‐complex antibody (LGI1 and CASPR2 in the VGKC antibody) were studied by Oxford Universy Immunology Labratory. Results: The study included 44 girls (44%) and 56 boys (56%) with a mean symptom age of 8.6 ±4.53 years (range:9 months-­‐18 years). ANA was positive in 15(18.8%), antiphospholipid Ab in 3(3.75%), anticardiolipin Ab in 1(1.25%), anti-­‐
thyroid peroxidase in 3 (3.75%) epilepsy patients. Additionaly anti-­‐GAD Ab was positive in 7(8.75%), anti– Yo Ab 3 (3.75%), and anti-­‐Ma2 in 3 (3.75%) epileptic patients. Anti-­‐VGKC was positive in 6 (7.5%) epileptic patients. None of the patients were positive for anti-­‐LGI1, CASPR2 and NMDA. In 32 (40%) of 80 patients with epilepsy had at least one antibody positivity, whereas it was 3 (15%) in control patients (p=0,039). Conclusion: We performed a pioneer study to investigate the association of autoimmunity and pediatric epilepsy and we believed that autoimmunity should be considered in epileptic patients with undetermined etiology. P84 -­‐ 1546 Metabolic syndrome in children with epilepsy on valproate and phenytoin monotherapy: a cross-­‐sectional study Dhir A, Sharma S, Aneja S. Lady Hardinge Medical College and Kalawati Saran Children's Hospital, Gurgaon, India -­‐ [email protected] Background: Metabolic syndrome is a well recognized complication of valproate therapy. However there is paucity of data on the prevalence of metabolic syndrome in children with epilepsy on valproate monotherapy. Objective To compare the prevalence of metabolic syndrome between children on valproate and phenytoin monotherapy. Methods: Children aged 3-­‐16 years with epilepsy on valproate or phenytoin therapy for at least 6 months were enrolled. They were evaluated for the presence of abdominal obesity, dyslipidemia, glucose intolerance and hypertension. Metabolic syndrome was diagnosed when 3 of the following criteria were met: elevated fasting glucose (>100mg/dl), hypertension, high triglyceride levels or abdominal obesity. The prevalence of metabolic syndrome and abnormalities in the individual parameters were compared between the two groups. Results: Four out of 57 valproate-­‐treated children (41 males, 16 females) and none of the 53 phenytoin-­‐treated children(37 males,16 females) had metabolic syndrome.The baseline characteristics including age and duration of therapy were comparable in both groups.Mean serum triglyceride levels were higher in the valproate group as compared to the phenytoin group (94.97 ± 38.58 mg/dl versus 77.60 ± 11.44 mg/dl, p<0.05). The total cholesterol values were also significantly greater in valproate treated children as compared to the phenytoin group (148.28 ± 25.95 mg/dl versus 132.83± 23.51 mg/dl, p<0.05).The serum fasting glucose was not significantly different in the two groups. Conclusion: The prevalence of metabolic syndrome and dyslipidemia was higher in valproate treated children as compared to phenytoin treated children with epilepsy. Children on valproate treatment need to be monitored for the development of metabolic syndrome. P85 -­‐ 1545 Myoclonic-­‐astatic epilepsy: seizures outcome Shoukry I, Girgis MY, Abdel Ghaffar HM. Cairo Univertsity, Egypt -­‐ [email protected] Objectives: Myoclonic astatic seizures have variable course and outcome. Spontaneous remission with normal development has been observed in some untreated cases of MAE. The purpose is to follow the outcome of MAE in relation to treatment modalities and associated seizure phenotypes. Material &Methods: Thirty children with MAE of idiopathic etiology with mean age at seizure onset 27 ±11.6 months; (24 males, 6 females) from neuropediatric unit Cairo University. Twenty percent had family history for epilepsy and 13.3% for febrile seizures. Digital EEG and MRI brain were done for all. Results: Patients were classified into 2 groups, group1 with complete seizure remission (76.6% n=23) and group2 (23.3% n=7) with ongoing seizures despite appropriate treatment over at least 6 months. Presenting seizure type was MAE in 66.6%, while GTCs and astatic seizures in 125 23.3% and 6.6% respectively. In group1, 44% had only one type of seizure namely myoclonic astatic while 56 % had more than one type GTCs , absence or atonic fits. In group 2, 100% had more than one seizure type (p-­‐value 0.033). EEG was normal in 40% of group1. Valproic acid was the most frequently used AED (83.3%) with the highest remission rate (80%) followed by clonazepam, lamotrigine, ethosuximide respectively. In group 2, 100% were on polytherapy while 26% of patients in group1 achieved complete remission on monotherapy. Sixty four percent were achieving normal development; most of them belonging to group1. Conclusion: The overall prognosis, despite initial resistance to treatment, is good. The outcome is not dependant on age of seizure onset, severity of EEG findings or duration of disease before remission. It is highly dependent on variability of seizures with worse prognosis when more than one seizure type occurred. The seizures switch off (remission) can occur at any time of the disease. P86 -­‐ 1541 Prevalence of genetic polymorphisms of UGT1A6 and their association with serum valproate levels in north Indian children with epilepsy on valproate monotherapy Puneet Jain, Sheffali Gulati, Shivaram Shastri, Madhulika Kabra, Gupta YK, Ravindra Mohan Pandey, Neerja Gupta. Division of Pediatric Neurology, AIIMS, Delhi, India -­‐ [email protected] Objectives: There is marked inter-­‐individual variability in the pharmacokinetics and pharmacodynamics of valproate. Polymorphisms in UGT1A6, one of the major enzymes involved in the hepatic glucuronidation of valproate, may partly explain this. This study aimed to assess the association between the genetic polymorphisms of UGT1A6 in Indian children with epilepsy and the pharmacokinetics of valproate. Methods: This cross-­‐sectional study was carried out in the Department of Pediatrics, AIIMS, New Delhi, between March 2011 and July 2012. Children aged 3-­‐12 years of North Indian Origin diagnosed as epilepsy on valproate monotherapy for at least 1 month were enrolled. They underwent a detailed clinical examination as per a pre-­‐designed proforma. The UGT1A6 polymorphisms were detected by PCR-­‐restriction fragment length polymorphism. Random samples were checked by genetic sequencing. The steady state plasma concentrations of valproate were measured by High Performance Liquid Chromatography (HPLC) and associated with UGT1A6 polymorphisms. Results: The most common etiological causes of epilepsy were neurocysticercosis (37.5%) and cerebral palsy (30%). The mean age at seizure onset was 5.6 ± 3.4 years. The mean dose of valproate was 21.8 ± 9.1 mg/kg/day. The prevalence of UGT1A6 T19G was as follows: TT (45%), TG (38.8%) and GG (16.3%); that of UGT1A6 A541G was: AA (48.8%), AG (38.8%) and GG (12.5%); and that of UGT1A6 A552C was: AA (43.8%), AC (40%) and CC (16.3%). There was no significant association between valproate doses or standardized serum valproate concentration and the various UGT1A6 genotypes. Conclusions: Although no significant association was found between valproate doses or standardized serum valproate concentration and the various UGT1A6 genotypes, larger studies, studies in different ethnic backgrounds and meta-­‐analyses of current data will help clarify the functional impact of UGT1A6 polymorphisms. P87 -­‐ 1529 Evaluation of adherence to a convulsion management protocol for children in Rwanda Kaputu KMC, Birindabagabo J-­‐D, Mafuta ME, Walker TD, Misson J-­‐P. Service of Child Neurology, Mons, Belgium -­‐ [email protected] Background: Prolonged seizures occur frequently among children in sub-­‐Saharan Africa and are known to be associated with high morbidity and mortality. Inappropriate treatment may be one of the causes of this tragic situation. Objective: Assess the adherence of health professionals in southern Rwanda to a national protocol for pharmacological management of seizures in children. Method: A questionnaire featuring a 5 year old child with generalized seizures lasting longer than 5 minutes was administered to doctors and nurses working in hospitals in the Southern Province of Rwanda. The questions focused on the choice of initial treatment and the sequence of management following failure of the initial treatment choice. Results: The questionnaire was answered by 60.5% (129/213) of those surveyed. On substantive issues, there was no statistically significant difference in responses between physicians and nurses. Benzodiazepine was chosen as initial therapy by 93.7% of physicians and 90.9% of nurses. Only 49.2% of physicians and 41% of nurses would repeat the initial treatment in case of failure of the first dose and 47% of doctors would wait 30 minutes to intervene. 34% of physicians would give 3 doses of benzodiazepine. 57% of them were unsure of the time to wait between the second and third dose of anticonvulsant, while 19% did not know what to do in case of refractory status epilepticus. Conclusion: These results suggest poor adherence to national protocol. Further education would contribute to improved management of prolonged convulsions in Rwanda. 126 P88 -­‐ 1520 Hormonal treatment in the management of infantile spasms Altynshash Jaxybayeva, Raushan Kenzhegulova, Dinara Kazhaparova. National Research Center for Mother and Child Health, Astana, Kazakhstan -­‐ [email protected] Background: Infantile spasms (IS) is an uncommon epilepsy syndrome that typically begins in infancy. IS are considered to be a "catastrophic childhood epilepsy" due to the difficulty in controlling its symptoms and the developmental problems that can occur as a result of the condition. The triad of spasms, arrest of psychomotor development, and hypsarhythmia is known as West syndrome. The goal of treatment is to eliminate the spasms and hypsarrhythmia as quickly as possible. Awareness and proper identification can result in the selection of appropriate therapy that can improve a patient's developmental outcomes. There is no consensus on the best initial approach for infantile spasms. Many experts recommend a short course of hormonal therapy (ACTHar) but others use oral antiepileptic drugs (vigabatrin or topiramate) or oral steroids (prednisolone). Purpose: to identify a most appropriate way for management of IS in Kazakhstani patients and compare cognitive development and seizures control between subgroups with and without hormonal treatment (ACTH or dexametazone and valproates). Patients and methods: 25 children 3-­‐11 month of age with IS (most of them diagnosed as a West syndrome, one had an Aicardi syndrome) were analyzed during 2011-­‐2013. Results: we had three groups of patients who were treated with different ways. One group had a treatment with ACTH. Second group were treated with dexametazone and third group were treated by valproates. Conclusion: First and second group had a reduction of seizure activity during first week of hormonal treatment in 80%. Cognitive improvement after 5th day of treatrment was reported by all mothers. Long term seizures free period at first and second group during 6 months – 80% and during 12 month-­‐ 60%. At third group we got positive results after three weeks of treatment by valproates. Seizures free period were not be reached. P89 -­‐ 1517 Clinical audit of an established paediatric transient loss of consciousness (“blackouts”) clinic Randhay AS, Thakker P, Whitehouse WP. School of Clinical Sciences, University of Nottingham, UK -­‐ [email protected] Objectives: The study intended to highlight processes that could be improved and evaluate the usefulness of paediatric transient loss of consciousness (TLoC) clinics. It also explored the management of patients with neurally mediated syncope (NMS). Methods: Clinical documents were examined and evaluated against a compiled list of processes deemed necessary in a TLoC clinic. The outcome measure was change in frequency of symptoms after one year of follow-­‐up. Results: 57 patients aged 1 to 17 years (median 13) were audited. The rates for the clinic’s documented processes were: 100% for history of presenting complaint and description of events; 98% for drug and medical history; 93% for triggers and blood pressure; 91% for family history, 82% for lying and standing blood pressure and heart rate; 79% for neurological examination; 68% for cardiovascular examination; 70% for a standard 12-­‐lead electrocardiogram. In addition 46% had an EEG and 44% a head-­‐up tilt test. In 33% of patients the diagnosis changed significantly by one year of follow-­‐up. 32/46 (70%) patients with TLoC had 50% or fewer events after one year including 23/46 (50%) symptom-­‐free for the last 6 months of follow-­‐up. 16/35 (46%) patients with pre-­‐syncope had 50% or fewer episodes after one year of follow-­‐up, including 6/35 (17%) who were symptom-­‐free in the last 6 months. Conclusions: The documentation rate should have been 100% for the processes listed (excluding EEG and head-­‐up tilt test) as they are recommended in the existing literature. Better documentation and the use of a checklist could improve these rates. The clinics’ promising outcomes pave the way for future studies and drug trials. The audit showed the need for paediatric TLoC guidelines to help general practitioners and paediatricians manage TLoC more actively. It also highlights the importance of using the right diagnostic tests to increase the quality of diagnoses. P90 -­‐ 1515 Effects of Oxcarbazepine on the language and problem solving abilities in newly diagnosed pediatric epileptic patients Sun Jun Kim, Ju Hong Min, Kyeoung Sook Kim. Dept of Pediatrics, Chonbuk National Univ Medical School, Korea -­‐ [email protected] Purpose: The purpose of this study was to determine the effects of oxcarbazepine on the problem solving abilities in newly diagnosed pediatric epileptic patients. Patients and Methods: Thirty newly diagnosed pediatric epileptic patients (Male:Female=14:16, Mean age :10.5y ¡¾ 3y), who were investigated from April 2006 to Oct 2012. We performed a standardized full articulation tests and Peabody picture vocabulary test-­‐revised (PPVT-­‐R). Test of Problem Solving (TOPS), Mean Length of Utterance in words (MLU-­‐w), comparison of Precise Articulation, Computerized Speech Lab were used to assess the language function before and after initiation of 127 oxcarbazepine. Starting dosage of oxcarbazepine was 10mg/kg for the first 7days; increased to 20mg/kg for the next 7 days and increased up to 30mg/kg/day (or 1,200mg/day). The mean dosage of oxcarbazepine was 25 mg/kg/day. Results: First, TOPS showed that the abilities of problem solving were improved after initiation of oxcarbazepine {(total score: 35.6 ¡¾ 14.8 vs 40.1 ¡¾ 13.2, P<0.05), Causal reason parameter (11.0 ¡¾ 4.3 vs 12.1¡¾4.2), solution ratiocination (15.3 ¡¾ 6.2. vs 16.9 ¡¾ 6.9), beginning guess (9.3 ¡¾ 5.3 vs 10.9 ¡¾ 4.3)}. Second, MLU-­‐w did not reduce after taking medicine (4.8¡¾1.4 vs 4.9¡¾1.4). Third, the receptive language function was significantly improved after taking oxcarbazepine in PPVT (9y 6m ¡¾ 3y 3m vs 10y 2m ¡¾ 3y 5m, P<0.05). Conclusion: Our results suggest that oxcarbazepine can be used without significant negative effects on language function. Moreover, language functions, especially receptive language, were improved after oxcarbazepine initiation. P91 -­‐ 1510 Polymorphism of SCN1A and SCN2A gene in pediatric refractory epilepsy patients Keon Su Lee, Joon Won Kang, Dong Woon Kim. Department of Pediatrics, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea -­‐ [email protected] Objectives: Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures. While there have been many break throughs in development of antiepileptic medications, the cure for epilepsy still needs many answers, such as genetic aspects of the illness. Gene mutation may contribute to this situation. In this study, we have evaluated children with single nucleotide polymorphisms (SNP) of SCN1A c.3184 A¡æG (rs2298771) and SCN2A c.56 G¡æA (rs17183814) to analyze these genes were associated with refractory seizure. Materials and Methods: Three hundreds and eleven children who visited the outpatient clinic in Chungnam National University Hospital, were retrospectively reviewed and, the data for their demographic profiles, clinical characteristics, and the results for SNP of SCN1A and SCN2A gene were collected. We divided them into three groups of control, response, and refractory groups. Results: There was no statistical difference in demographic profiles of the patients. A variant of SCN2A c.56 G¡æA polymorphism was associated with refractory seizure in pediatric patients with epilepsy (p=0.004; odds ratio 2.78, 95% confidence interval 1.39-­‐5.56). Conclusions: SNP of SCN2A c.56 G¡æA could be suggested as one of the causes of pediatric refractory epilepsy. P92 -­‐ 1507 Association between hypocapnia and febrile seizures Kýlýçaslan B, Erol I, Ozkale Y, Saygi S, Sarýtürk C. Baskent University Faculty of Medicine, Department of Pediatrics, Adana Teaching and Medical Research Center, Turkey -­‐ [email protected] Objectives: The pathogenesis of febrile seizures is not clear even today. Despite evidence from both animal models and adult humans, this is only the second study to measure pCO2 and pH values in children with febrile seizures. The purpose of this study is to determine whether hyperthermia-­‐induced hyperventilation with subsequent hypocapnia is relevant to febrile seizures in children. Materials and Methods: This prospective case-­‐
control study enrolled 18 children who presented with febrile seizures and 18 children who presented with a febrile illness without seizures between October 2012 and January 2013. Blood gas analyses were measured both from the febrile seizure and control group. Results: There was no significant difference in mean blood pH between the febrile seizure and control groups but blood pCO2 was significantly lower in the febrile seizure group. Patients with complex febrile seizures exhibited significantly lower pCO2 levels within 1 hour of seizure onset than patients with simplex febrile seizures. Conclusions: These data indicate that febrile seizures may be associated with hyperventilation and that the ensuing hypocapnia may contribute to the development of a seizure disorder. P93 -­‐ 1504 New cases of triple syndrome Popova VA, Afonin AA, Shokarev RA, Baybikova GSh, Timolyanova EK. Rostov Scientific-­‐Research Institute of Obstetrics and Pediatrics, Rostov-­‐on-­‐Don, Russia -­‐ [email protected] TRIPLE syndrome is a rare autosomal-­‐recessive pathology which is characterized by hypocorticism, melanoderma, achalasia of esophagus, alacrimia. Proband D, 5 years old. Parents came for a consultation as the child had convulsive disorder, melanoderma and had no tears when crying. Skin pigmentation was recorded for the first time at the age of 2, it gradually increased, at the age of 2.5 the boy was operated for achalasia of the cardiac part of esophagus. At the same age a low level of blood cortisol with the normal range of glycemia was detected, chronic adrenal insufficiency was diagnosed. By diagnosis specification blood cortisol decrease reached 0.2 MOM. The first convulsive clonicotonic attack with the loss of consciousness was also registered at the age of 2.5. Further on it repeated approximately once in a year in spite of the therapy conducted. According to EEG data 128 epiactivity was not registered. Proband Z., 8 years old, was sent for examination concerning convulsive disorder, hypomnesia, melanoderma and alacrimia. Swarthy skin pigmentation was noticed at the age of 5. At the age of 6 and 7 – two episodes of clonicotonic convulsions with long impairment of consciousness (up to 12 hours) on the background of a normal level of blood glucose. EEG registered moderate paroxysmal activity of subcortical genesis. By laboratory examination a very low level of blood cortisol (0.2 MOM), increase of ACTH (5.1 MOM) and TSH (4 MOM) were detected. On the background of treatment with hydrocortisone children’s condition improved, content of cortisol in blood increased up to 0.8 – 1.0 MOM, biorhythm of its secretion restored. It is of interest that both children have the episyndrome which is refractory to standard anticonvulsive therapy in the absence of substantial changes of EEG, earlier it was not described in case of such pathology. P94 -­‐ 2054 Two Patients With Infantile Epileptic Dyskinetic Encephalopathy And Late Diagnosis of Focal Cortical Anomaly Kara B, Maras H, Yalcin EU, Aktan F, Demirbas F. Kocaeli University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Kocaeli, Turkey -­‐ [email protected] “Early-­‐Infantile Epileptic Encephalopathy (EIEE) with Suppression-­‐Burst” is the most severe and earliest form of age-­‐related epileptic encephalopathy with heterogenous group of etiology including cortical malformations, hypoxic ischemic encephalopathy, inborn errors of metabolisms and specific genetic defects. We present two patients with EIEE and severe dyskinetic movements. Patient 1 is 21-­‐month-­‐old-­‐boy and patient 2 is 2.5 year-­‐old boy. Both patients had uneventful prenatal and natal history. The intractable seizures started on the first day of their lives, severe dystonic posture was relevant and “burst-­‐suppression” pattern was seen on the EEG. Extensive metabolic work-­‐up including blood chemistry, complete blood count, serum ammonia and lactate levels, serum and cerebrospinal fluid (CSF) quantitative amino acid levels, Tandem MS/MS, urine organic analysis, CSF neurotransmitter levels were normal. Initial cranial magnetic resonance imaging (MRI) taken during the neonatal period was normal. Aristaless-­‐related homeobox (ARX) gene was not found in both patients. We thought that the patients had a genetic defect causing infantile epileptic dyskinetic-­‐encephalopathy and planned to study other genes reported to be responsible in EIEE. However, the video-­‐EEG in the first patient recorded when he was 17-­‐
month-­‐old revealed multiple seizures originating from the left temporal lobe. The repeated cranial MRI revealed cortical anomaly in the left temporal lobe. Positron emission tomography (PET) study of the second patient revealed right fronto-­‐temporal hypermetabolism and MRI revealed a probable right fronto-­‐temporal cortical anomaly. The first patient underwent lesionectomy and the second patient has been prepared for epilepsy surgery. P95-­‐ 1984 Treatment of epilepsy in 6 patients with MECP2 Duplication Syndrome Hasse A, Haberl C, Betzler C, Hasselmann O, Maier O, Shimada S, Biro A, Selch C, Staudt M, Kluger G. Neuropädiatrie, Schön Klinik Vogtareuth, Germany -­‐ [email protected]­‐kliniken.de Objectives: Increasing use of Array CGH leads to increased diagnosis of MECP2 duplication syndrome. Male and female patients can be affected with different phenotypes (Bijsma et al. 2012). The most common features in affected boys are infantile hypotonia, global developmental delay, intellectual impairment, autistic traits, poor or absence of speech, recurrent respiratory infections and seizure (Ramocki et al. 2010). Seizures occur in > 50% of children and >90% of adolescent patients. Age of onset, inter-­‐ and intraindividual types are variable. Until now, no antiepileptic drug has been found to be particularly suitable. Anecdotically benzodiazepines do offer the best treatment to drop attacks (Ramocki, pers. com.). Swallowing difficulties are although frequent (>50%, Ramocki et al. 2010) and from our own experience, could be associated with seizure frequency. Materials and Methods: Retrospective case evaluation of 6male patients (age: 3-­‐14) with MECP 2 duplication syndrome with regard to seizure type, antiepileptic drugs and swallowing difficulties. Results: The following seizure types were observed: Drop attacks/ head dropping (6/6), generalized-­‐tonic–clonic seizures (6/6), focal tonic seizures (4/6), atypical absences (2/6), myoclonic seizures (2/6). All patients had swallowing difficulties. 12 different AEDs were used as monotherapy or in combination: TPM, VGB, ZNS, AZA (1/6), RUF, LEV, CLB, STM, CZP (2/6), LTG, ESM (3/6). 6/6 were treated with VPA, 1/6 showed seizure reduction for some weeks, the others no lasting success. 3/6 patients had benzodiazepines. One patient became seizure free for at least 6 month with Rufinamid and Clonazepam associated with increased swallowing ability. None underwent epilepsy surgery, none were treated with ketogenic diet or VNS. Aggravations are not described. Conclusions: Epilepsy in children with MECP2 duplication syndrome is difficult to treat. Further collaborated clinical observations and data collections are needed in order to develop treatment recommendations. 129 Headache P96 -­‐ 2079 Significance of continuous performance test in children with headaches Kon-­‐Hee Lee, Saet Byul Woo. Hallym University Medical Center, Korea -­‐ [email protected] Purpose: The study examines the continuous performance test (CPT) in children with headaches. Headaches in children have known to be associated with the difficulty in concentration or school performance. But limited data are available for the measurement of attention deficit or changes of attention after treatment in relation with pediatric headaches or CPT. Materials and Methods: We enrolled 14 children and adolescents at Kangnam Sacred Heart Hospital during March to August in 2012, suffering from primary headaches according to diagnostic criteria of the international classification of headache disorders (ICHD-­‐II). The control group was 14 patients with ADHD and no history of recurrent headaches. All of them were assessed using advanced test of attention (ATA), one of CPT, during the headache attacks and after medication for treatment. Results: The auditory ADHD indexes (AI) of headache patients were as high as that of control ADHD group. The visual and auditory AI of the headache patients in some parts were improved after treatment. Conclusion: During the headache attacks, attention of children with headaches was as disable as ADHD patients in the CPT. The patients showed statistically improvement of clinical symptoms and AI after treatment. The CPT was efficient test to assess the degree of disability and improvement after treatment in attention of pediatric headaches. P97-­‐ 2066 Effectiveness of therapeutic measures in paediatric migraine Legisa S, Krvavica K, Rogac M, Rener Primec Z | Department of Child, Adolescent and Developmental Neurology, Children`s Hospital, University Medical Centre Ljubljana, Slovenia -­‐ [email protected]­‐lj.si Objective: The aim of the study was to determine the effectiveness of therapeutic measures in paediatric migraine. Patients and Methods: 150 children who were diagnosed with migraine with or without aura by International Headache Society criteria in a period of one year in our tertiary hospital were included in the study. Questionnaire about therapeutic measures and outcome of migraine in this group was sent to all children. Data received from 79 children were evaluated. Results: Therapeutic measures that were most effective in acute treatment of migraine headache were sleep in 75% (59/79), NSAID in 71% (32/45) and acetaminophen in 61% (42/69). More than 85% of children took the drug the right time and in appropriate dose. 22% (17/79) of children were prescribed with migraine-­‐specific treatment (sumatriptane in 88% (15/17), aspirin migran 6% (1/17) and pizotifen 6% (1/17)). Migraine prophylaxis was perscribed in 28% (22/79). Most common measures were 50 mg of riboflavin in 55% (12/22), acupuncture in 27% (6/22), and 50 mg of coenzyme Q10 in 9% (2/22). Riboflavin prophylactic treatment was effective in 42% (5/12), acupuncture in 67% (4/6) and coenzyme Q10 in 50% (1/2). Conclusions: The most effective treatment for treatment of acute migraine headache with or without aura in our study was sleep, with NSAIDs and acetaminophen as most common used effective analgesics. Relatively low percentage of children was prescribed migraine-­‐specific treatment and/or prophylaxis. Riboflavin, acupuncture and coenzyme Q10 show promising results for migraine prophylaxis in children, but were used in a small subgroup of children. P98 -­‐ 2037 Une crise de migraine hémiplégiante familiale atypique et réaction paradoxale au Topiramate Loiseau Y, Comte A, Amsellem D, Altuzarra C. Service de médecine Pediatrique CHRU de Besançon, France -­‐ [email protected] Resume: La migraine hémiplégiante familiale (MHF) peut se révéler par diverses présentations cliniques, parfois atypiques. Nous en rapportant une nouvelle observation clinique caractérisée par la survenu d’un coma. Sujet : Il s’agissait d’une patiente de 2 ans et demie aux antécédents personnels et familiaux de MHF avec mutation du gène ATP1A2. L’enfant a présenté un épisode d’hémiparésie à bascule dans un contexte fébrile à 40°C associé à un état de coma vigile. Le bilan para-­‐clinique (EEG, IRM encéphalique, ponction lombaire avec PCR herpès, fond d’œil) était normal en dehors de quelques lésions ischémiques corticales de petite taille, mises en évidence à l’imagerie cérébrale. L’évolution était favorable sous traitement symptomatique et Topiramate. Secondairement, la patiente a présenté des troubles du comportement avec régression du langage, irritabilité et cris stridents Ces symptômes n’ont alors régressé qu’à l’arrêt du traitement. Conclusion : L’état de coma est une manifestation clinique rare dans les crises de MHF. Différents médicaments antiépileptiques peuvent être utilisés pour limiter la fréquence des crises. Dans cette observation, le traitement par Topiramate était responsable de troubles du comportement régressant dès l’arrêt de celui-­‐ci. 130 P99 -­‐ 1850 Altered pain perception in children with chronic tension-­‐type headache: Is this a sign of central sensitisation? Soee AL, Thomsen LL, Tornoe B, Kreiner S, Skov L. Department of Paediatrics, Children’s Headache Clinic, Copenhagen University Hospital Herlev, Denmark -­‐ [email protected] Aim: To investigate if children (7-­‐17 years) with frequent episodic tension-­‐type headache (FETTH) or chronic TTH (CTTH) have an altered pain perception compared to healthy controls. Methods: We applied a pressure of 5 increasing intensities to m. trapezius and m. temporalis with a Somedic Algometer II. Visual analogue scale-­‐score was rated and Area under the curve (AUC) calculated. An average AUC in each person was used as outcome variable in further univariate multiple linear regression analysis, because factor analysis showed that AUC represents only one dimension underlying both muscles. Results: Participants: 22 children with FETTH, 36 children with CTTH and 57 controls. The CTTH group had a significantly higher AUC compared to the control group (P < 0.001). The FETTH group represented an intermediate state. AUC did not change with increasing age, headache years, headache intensity, headache frequency or sex. Conclusion: Children with CTTH show significantly increased pain sensitivity in a range of pressures compared to the FETTH group and the controls. Since AUC in m. trapezius and m. temporalis represents only one general latent tenderness, it might indicate that the altered pain perception is mainly due to central sensitisation. P100-­‐ 1629 TGFB1 genetic polymorphisms in pediatric migraine patients Saygi S, Alehan F, Erol I, Ataç FB. Baskent University Faculty of Medicine, Department of Pediatrics, Division of Child Neurology Adana Teaching and Medical Research Center, Turkey -­‐ [email protected] Objectives: The pathogenesis of migraine is known to be related to the presence of genetic polymorphisms, including those of cytokine-­‐ related genes. However there is no information about the role of Transforming growth factor-­‐β1 (TGFβ1) in the pathogenesis of pediatric migraine. Therefore we investigated polymorphisms in the TGFβ1 gene in relation to the migraine. Materials and Methods: The study included 100 consecutive children and adolescents in whom migraine was diagnosed according to the International Classification of Headache Disorders, as well as 98 healthy children and adolescents at the Baskent University Ankara and Adana hospital. Genomic DNA was investigated for 4 polymorphisms in the TGFβ1 gene 800 G/A, 509 C/T, codon 10, and codon 25. Results: In total 28 patients were defined as migraine with aura (MWA), 72 were defined as migraine without aura (MWoA). The mean ages of the children in the MWA group, MWoA group and control group were 14,36± 1,93, 12,97± 2,63, and 10,67± 3,44 years, respectively. No significant differences in genotypic distributions among MWA or MWoA patients and controls were observed in the polymorphism of 800 G/A and C25. Genotypic distributions of 509 C/T among patients with migraine and control groups also were not significant. However, the genotypic distribution of 509 C/T, was significantly different between control and MWoA patients. The C10 C/T genotypic and C10 C allelic frequency of TGFβ1 polymorphism was significantly higher in MWA or MWoA patients than healthy controls. Conclusions: In conclusion, the present results indicate the possible contribution of TGFβ1 gene polymorphisms to migraine headache generation in children. To our knowledge it is the first time that a relationship between TGFβ1gene polymorphisms and migraine is shown in pediatric age group. Further studies on this subject are needed, along with a search for new therapeutic agents with anti inflammatory properties. P101 -­‐ 1628 Body mass index and headache in school children: a nation-­‐wide survey Young-­‐Il Rho, Hee-­‐Jung Chung, Kon-­‐Hee Lee, Baik-­‐Lin Eun, So-­‐Hee Eun, Sang-­‐Ook Nam, Won-­‐Seop Kim, Young-­‐Ok Kim, Ho-­‐Jin Park, Hyeon-­‐Sook Kim. Department of Pediatrics, School of Medicine, Chosun University, Gwangju, Korea -­‐ [email protected] Background: Body mass index (BMI) is associated with headache prevalence, frequency and severity of headache and disability, but it is controversial. Obesity is risk factor with chronification within subjects with episodic headaches. Recently, it was reported that obesity occurs at a higher rate in children presenting to tertiary pediatric headache center compared with the general population. Purposes: To access the relationship of BMI to the prevalence, frequency, duration, severity of headache, and chronic headache in school children in Korea. Methods: We conducted a cross-­‐sectional school-­‐based study of randomized and proportional sample of 3493 boys and girls. The questionnaires collected demographic data in addition to specific questions about headache according to the ICHD-­‐2 criteria. The BMI calculated and the BMI percentile determined. Results: The prevalence of headache was 29.0% (1013/3493) among in South Korea. The prevalence of headache in girls (33.2%) was significantly higher than in boys (25.0%) (P<0.001). The prevalence of chronic headache in girls (3.2%) was 131 significantly higher than in boys (1.3%) (P=0.013). The prevalence of overweight school children with headache (9.8%) did not significantly differ from the overweight school children (11.9%). The prevalence of chronic headache in overweight children (10.1%) was higher rate than in non-­‐overweight children with headache (7.5%). BMI percentile was not significantly correlated with headache frequency, severity, and duration. Conclusions: The prevalence of overweight school children with headache did not significantly differ from the overweight school children without headache. Obesity was higher rate in school children with chronic headache in Korea, similar to findings of other studies. The frequency, duration, and severity of headache were not associated with obesity. P102-­‐ 1536 The role of vitamin D supply and its impact on headaches in children and teenagers Potrykus AJ, Pilarska E. Department of Developmental Neurolgy, Medical University of Gdañsk, Poland -­‐ [email protected] Objectives: There is little evidence on the impact of cholecalciferol on headaches despite the building evidence on its role in brain, and the widespread vitamin D deficiency. The aim of the study is to verify whether vitamin D supplementation reduces strength or frequency of headaches and if the used dosages and to assess the efficacy of the doses recommended by experts. Materials and Methods: Children and adolescents diagnosed with migraine and/or tension-­‐type headaches, with no other coexistent neurological diseases, were tested for vitamin D serum level (25OHD=25-­‐hydroxycholecalcyferol) after obtaining written informed consent from parents. They were provided with prescription for cholecalciferol drug in liquid drops and advised to supplement vitamin D depending on the deficiency level. Levels and doses were defined as follows: below 10 ng/mL -­‐ 5000 IU/day; 10-­‐
20 ng/mL -­‐ 2000 IU/day; 21-­‐29 ng/mL -­‐ 1000 IU/day; 30-­‐60 ng/mL -­‐ 500 IU/day. The 25OHD levels were assessed at 3 and 6 months, additionally at 1 month if 5000 IU/day were given. Each patient received headache diary designed for the duration of the study – 6 months. Results: The study is on-­‐going. Of 37 patients tested, 27 had 25OHD level below 20 ng/mL (considered deficiency), no one exceeded 30 ng/mL. The patient’s parents generally declare a reduction in headaches strength after 3 months of vitamin D supplementation. The recommended cholecalciferol doses used in deficiency are not sufficient in some cases to observe the demanded increase in 25OHD level (>30 ng/mL) after 3 months. Conclusions: Vitamin D deficiency is widespread among children with headaches from northern Poland. Further studies are needed on the impact of vitamin D on headaches in children, teenagers and adults. Immunology P103 -­‐ 2052 Acute subdural hematoma as a complication of varicella zoster virus infection in a 2 year old child Aziz M, Kaliaperumal C, Allcutt D. Children's University Hospital, Temple Street, Ireland -­‐ [email protected] A. Background: Intracranial haemorrhage (ICH) in varicella zoster virus (VZV) infection is rare. 2 cases have been reported as subarachnoid haemorrhage secondary to VZV vasculitis and ICH two months post varicella infection. To our knowledge this is the first case of acute subdural and intracerebral haemorrhage secondary to coagulopathy caused by VZV infection. B. Case description: A 2 year old previously healthy male child presented with 6 day history of chicken pox infection and bilateral facial and neck swelling. The oedema compressed his upper airway and child was intubated and ventilated. The neck swelling on the left was complicated by cellulitis and ulceration. The clinical course deteriorated to septicaemia and hypotension with renal and liver failure, coagulopathy and rectal bleeding. Two weeks later he developed bilaterally fixed pupils. C. Results of investigations: Peripheral blood culture and tests confirmed superimposed Group A Streptococcus (GAS) septicaemia and thrombocytopaenia, abnormal liver function test and prolonged clotting time. Emergency MRI brain prior to neurosurgical intervention showed a very large left subdural hematoma associated with significant midline shift causing ischaemia to medial aspect of cerebral hemisphere, bilateral frontal lobes, left thalamus, midbrain, pons and contralateral occipital lobes. D. Treatment: Child underwent emergency left hemi craniotomy and evacuation of acute subdural hematoma and left occipito-­‐ parietal hematoma. Intraoperative findings were blood clot and products no pus seen. This was confirmed on analysis of theatre specimen. Post-­‐ operatively child underwent intensive multi-­‐ disciplinary rehabilitation and currently progressively recovering. E. Discussion: ICH is a severe complication of VZV infection. We infer that the superimpose infection of another micro-­‐ organism from the skin flora (GAS) as the main threat of ulcerated VZV infection that can lead to a catastrophic outcome. P104 -­‐ 2146 Atypical presentation of subacute sclerosing panencephalitis 132 Deniz Yüksel, Kenan Sonmez, Melek Boynukalın, Emrah Utku Kabataş. Dr. Sami Ulus Children's Health and Diseases Training and Research Hospital, Ankara, Turkey -­‐ [email protected] This report describes a patient with atypical features including hemiparesis, subacute vision loss, lack of myoclonus, and lack of specific electroencephalographic changes. Before admited to our clinic with vision loss,11 year old male had applied another hospital because of hemiplegia and misdiagnosed acute disseminated encephalomyelitis and steroid terapy had been started. On magnetic resonance imaging of brain, parieto-­‐
occipital corticosubcortical regions white matter signal intensities had become higher and supratentorial cortical atrophy was observed. Our neurological examination revealed left hemiparesis, mild mental retardation, and decreased visual acuity. Fundus examination revealed bilateral optic atrophy and chorioretinitis. A periodic electroencephalogram complex was absent. The diagnosis was confirmed with the identification of measles antibodies in the cerebrospinal fluid. Isoprinosine therapy was started. Physicians taking care of children need to be aware of atypical presentations of subacute sclerosing panencephalitis and avoid unnecessary diagnostic and therapeutic interventions. P105 -­‐ 2133 Acute encephalitis related to human herpesvirus type 6 (HHV6): two immunocompetent children with variable outcome Amsallem D, Pâris C, Devys-­‐Meyer N, Bévalot J, Camélio A. Department of Pediatric Neurology, University Hospital Jean Minjoz, Besançon, France -­‐ [email protected]­‐besancon.fr Direct infections of the brain can be caused by many viruses, bacteria, parasites and fungi. We describe two previously healthy boys with primary infection caused by HHV-­‐ 6. A 18-­‐month-­‐old French boy presented in 04/2012, with high fever, cough treated since two days with Amoxicillin, hypotonia, whimpers, vomiting, impaired consciousness, tonico-­‐clonic seizures. Previously, walk and some words were acquired. Neurological examination revealed no focal signs. Pneumonia interestingly the right upper lobe was confirmed by radiography. Initial laboratory tests were unrevealing, except CRP = 87 mg/ml. CSF was normal with no oligoclonal bands. Culture, antibody studies and polymerase chain reaction (PCR) of CSF were broadly performed. CSF contained high copy number of HHV-­‐6 DNA (2044 copies/ml). All other investigations remained negative. He was treated, initially, with broad-­‐spectrum antibiotics, acyclovir, clonazepam, phenytoin. MRI brain showed high signal intensities in diffusion-­‐weighted images in fronto-­‐parietal cortical and subcortical structures. The patient stayed in hospital for 15 days and recovered during six months in rehabilitation center from hypotonia, gait abnormality, mood disorder, poor swallowing and speech impairment. Motor impairment persists. A 6-­‐year-­‐old boy presented in 03/2013, with high fever, atonic seizure, comatose and pyramidal signs. Laboratory tests were unrevealing, except CRP = 20 mg/ml. CSF was normal with no oligoclonal bands. Culture, antibody studies and polymerase chain reaction (PCR) of CSF were broadly performed. CSF contained mild copy number of HHV-­‐6 DNA (740 copies/ml). All other investigations remained negative. He was treated, initially, with broad-­‐spectrum antibiotics, acyclovir, clonazepam, valproate. MRI brain showed high signal intensities in diffusion-­‐weighted images throughout the entire cerebral hemispheres, involving cortical and subcortical structures. The patient stayed in hospital for 21 days with intravenous ganciclovir. He recovered rapidly without neurorehabilitation or evidence of neurologic sequelae. Primary HHV6 infection is not always a benign illness and may require specific treatment. P106 -­‐ 2127 The importance of monitoring system epidemiologic acute flaccid paralysis for identifying cases of syndrome Guillain-­‐Barré in the capital of Brazil: the period 2007-­‐2011 Bomfim D, Melo MLA; Siqueira ES. Neurologist Paediatric Hospital Regional da Asa Sul -­‐ Brasilia, Brazil -­‐ [email protected] Introduction: Polio is a contagious infectious disease caused by poliovirus, more common in children. The system of surveillance of Acute Flaccid Paralysis (AFP) aims to maintain polio caused by wild poliovirus eradicated allowing differential diagnoses to identify patients suffering from Guillain-­‐Barré syndrome in pediatric patients to be among their differential diagnoses. Objectives: Describe the epidemiology of cases of Guillain-­‐Barré syndrome reported in the period January 2007 to January 2012 by the surveillance system of the AFP. Methodology: Conducted a retrospective analysis of data collected in Sheets AFP-­‐Epidemiological Research, available in SINAN, from January 2007 to January 2011. Results: There were 43 reported cases, the regional health Brasília greater number of cases were Ceilândia with 28.7% of cases; range with 14.28% and 9.52% in Santa Maria, the female was more prevalent with 52 %, the most affected age group is 0-­‐5 years old with 28.5%. Following the goals determined by the program found: 42 reported cases, 2 cases were diagnosed with open end. The 40 cases with a final diagnosis: 30% cases -­‐ Guillain Barré syndrome, 17.5% -­‐ Acute encephalitis and 10% -­‐ Periodic Paralysis. 133 Among the 43 reported cases, 30% was due to GBS, 17.5% for acute encephalitis and 25% of unknown etiology (Chart 4). The symptoms most frequently found were pain (55.8%), fever (48.8%) and vomiting (37.2%). Conclusion: The results demonstrate that the surveillance of AFP in Brasilia in the period 2007-­‐2010 was very sensitive to achieve the targets set for the indicators and the majority of cases reported had the diagnosis of Guillain-­‐Barré syndrome which is now the main differential diagnosis of poliomyelitis. P107 -­‐ 2099 Posterior reversible encephalopathy syndrome in our paediatric population Wang SJ Furene, Ong HT, Lin BY Jeremy, Tay KH Stacey, Yap HK. Singapore -­‐ [email protected] Objectives: Posterior reversible encephalopathy syndrome (PRES) is defined as new-­‐onset seizures, severe headaches, altered mental status or cortical visual changes. This may be accompanied by significant neuro-­‐
radiological changes. Common etiologies include hypertension, uremia and the use of calcineurin inhibitors such as cyclosporin A. There are few paediatric studies of posterior reversible encephalopathy syndrome as compared to adult studies. We aim to describe the clinical features, etiologies, neuroimaging changes and electroencephalogram findings in a group of patients with PRES. Materials and Methods: We analysed the data of six patients identified from August 2008 to July 2012 retrospectively. Results: 5 out of 6 patients had renal impairment and 1 had chronic liver disease. The patients with renal impairment presented with PRES due to uncontrolled hypertension and PRES in the child with liver disease was attributed to the usage of cyclosporin A. All 6 patients presented with seizures and 1 child had cortical visual changes, which completely resolved. Although most of the patients had neuroimaging findings of occipital and posterior parietal abnormalities, 2 of them had changes of the basal ganglia. Electroencephalogram performed showed abnormalities ranging from frontal sharp waves to generalized spike wave activity. Follow-­‐up neuroimaging studies performed showed resolution of the abnormalities. Conclusions: PRES should be recognized early as a complication of varying etiologies, and it can respond favourably to appropriate treatment such as optimal control of hypertension. The neuroimaging changes may not always be in the posterior white matter but are usually fully reversible. P108-­‐1741 Anti-­‐N-­‐Methyl-­‐D-­‐Aspartate receptor encephalitis in a child Aksoy A, Konuþkan B, Saygý S, Ozkan M, Çenesiz F, Yüksel D. Division of Pediatric Neurology, Department of Pediatrics, Dr. Sami Ulus Children's Health and Diseases Training and Research Hospital, Hacettepe University Children's Hospital, Baskent University Faculty of Medicine, Ankara, Adana, Turkey Anti-­‐N-­‐methyl-­‐D-­‐aspartate (anti-­‐NMDA) receptor encephalitis likely has a wider clinical spectrum than previously recognized. A wide variety of movement disorders, which stereotypic movements, ataxia, limb dystonia, limb myorhythmia, oromandibular dystonia, facial myorhythmia, blepharospasm, opisthotonus, athetosis, and tremor, often in combination, can be observed in children with anti-­‐NMDA encephalitis. We report a 6-­‐year-­‐old boy with anti-­‐NMDA receptor encephalitis without a detectable tumor who showed a nearly complete recovery after intensive immunotherapy. P109 -­‐ 1522 Anti-­‐NMDA receptor encephalitis: an unusual cause of autistic regression in a toddler Ori Scott, Lawrence Richer, Karen Forbs, Myroslava Eliyashevska, Helly Goez. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada -­‐ [email protected] Introduction: Anti-­‐NMDA receptor encephalitis in children is typically associated with prodromal viral-­‐like illness, followed by psychiatric changes (predominantly aggression), seizures, language dysfunction, dystonia, and dyskinesias. We present the first report of autistic regression in a toddler caused by anti-­‐NMDA receptor encephalitis. Case Description: A 33-­‐month old boy presented with decreased appetite, irritability, and insomnia following an upper respiratory tract infection. Over the course of the next few weeks he lost previously-­‐acquired language and social skills, finally becoming mute. Repetitive left hand movements and posturing appeared. Toe-­‐
walking and wring movements of the left wrist were observed. Within a month, this previously-­‐healthy patient came to fit the diagnostic criteria for Autistic Spectrum Disorder. Laboratory tests were normal, apart from mild elevation of liver enzymes, and increased CSF IgG index. Brain MRI was normal, and EEG revealed non-­‐specific background slowing with no seizures. Upon further investigation, CSF serology was returned positive for NR1 anti-­‐MNDA receptor antibodies. The patient was treated with intravenous immunoglobulins followed by 8 weeks of oral steroids, resulting in reacquisition of language and social skills, and resolution of hand posturing. Discussion: While most children diagnosed with Autistic Spectrum Disorder fail to attain communication and/or social skills in their first 2 years of life, up to one third of cases are characterizes by loss of previously-­‐acquired skills during toddlerhood. Given our incomplete understanding of the pathogenesis of Autistic Spectrum 134 Disorder, it is possible that autistic regression in some children may stem from an underlying autoimmune process, as found in our patient. Our case emphasizes the significance of suspecting anti-­‐NMDA receptor encephalitis as the cause of autistic regression. We caution physicians to maintain a high index of suspicion even in an age group where the diagnosis of Autistic Spectrum Disorder is typically made, and especially when presentation follows a febrile illness. P110 -­‐ 1561 A different presentation of anti-­‐N-­‐Methyl-­‐D-­‐Aspartate receptor encephalitis: anti-­‐N-­‐Metyl-­‐D-­‐Aspartate receptor encephalitis that developed after herpes encephalitis Bektaþ Ö, Tanyel T, Aldemir B, Fitöz S, Ýnce E, Deda G. Department of Pediatric Neurology, Ankara University Medical School, Ankara, Turkey -­‐ [email protected] Herpes encephalitis is one of the most common viral encephalitis. Brain abnormalities on MRI were significantly reduced in a mouse model of herpes infection when methylprednisolone was administered in combination with acyclovir, compared to treatment with acyclovir alone. Additionally, earlier publications reported that some patients developed choreoathetosis which was refractory to acyclovir after herpes encephalitis. These reports suggest the presence of secondary autoimmunity in the pathogenesis of herpes encephalitis. 19-­‐month-­‐old previously healthy girl presented with sudden onset of seizures and loss of consciousness. The initial HSV PCR was negative. Also limbic encephalitis antibodies were negative, we started steroids along with acyclovir due to the possible other autoimmune encephalitis and the patient had a history of varicella vaccine. HSV PCR was positive on the fifth day, but we continued the steroid treatment because the patiet had benefit from the treatment. Because of the upper respiratory tract infection steroid was reduced on the 25th day of treatment and the patient developed orofacial dyskinesia and choreoathetoid movements. The anti-­‐N-­‐Methyl-­‐D-­‐Aspartate Receptor antibodies was positive in serum and CSF on 28th day. This case supported the presence of autoimmunity in the pathogenesis of herpes encephalitis. Therefore we believe that the cases with previous herpes ensefalitis who benefited from steroids should be re-­‐evaluated in the light of this information. P111-­‐ 2090 VGKC antibodies: can become positive 4 weeks after presentation Singh J, Kashyape P, Kirkham F. Southampton General Hospital, UK -­‐ [email protected] Objective -­‐ To report a previously unreported characteristic of Voltage Gated Potassium Channel (VGKC) antibodies Materials and Methods -­‐ Retrospective review of case notes Results -­‐ 11 year old boy presented with acute onset focal seizures with occasional secondary generalisation. This was preceded by an upper respiratory infection approximately 2 weeks before seizure onset. He was also reported to have behavioural problems in the form of aggression which continued after seizure onset. His initial investigations all done within 1 week of seizure onset showed mild hyponatremia and mildly high signal in the left hippo campus which was felt to be secondary to the seizures rather than the cause for seizures. The EEG was encephalopathic and a left hemispheric electrographic seizure was noted during the recording with a left temporal origin. Urine organic acids, blood for lactate, ammonia, amino acid, acylcarnitines were negative. As the presentation was consistent with Autoimmune Encephalitis, extended antibody screen including against NMDAR, VGKC, GAD and others were negative at this time. Child was empirically treated for Autoimmune Encephalitis with high dose IV Methyl Prednisilone for 5 days followed by a tapering course. There was initial good response but seizures recurred within the week and so Levetiracetam was added. The repeat autoimmune screen, sent 4 weeks after seizure onset, confirmed the diagnosis of VGKC Encephalitis as the positive antibody result was reported. In view of this he was treated with intravenous immunoglobulin and responded favourably. It seems likely that he will require further immunomodulatory drugs. Conclusions: Our literature search did not bring up any reports of a similar presentation in which the antibodies became positive >4 weeks after initial presentation on repeat sampling in the paediatric population. This case adds an important and valuable vignette in the investigation and hence the treatment of this rare condition. P112-­‐ 2064 Acute necrotising encephalopathy in two children Diakogeorgiou A, Deconinck N, De Laet C, Dan B, Monier A. Department of Pediatric Neurology, HUDERF, ULB Brussels, Belgium -­‐ [email protected] Acute necrotising encephalopathy (ANEC) is a rare rapidly progressive paediatric encephalopathy. The MRI hallmark of the disease consists of symmetric, multifocal lesions in the thalami with variable involvement of the white matter, basal ganglia, brainstem and cerebellum. Pathogenesis is supposed cytokine mediated after viral infection. Mutations in RANBP2 have been recently associated with familial and recurrent cases of ANEC. Two 135 children aged 3 and 10 years old respectively, presented with high fever and respiratory tract infection. Both developed altered consciousness rapidly progressing to coma. The youngest presented focal seizures. Routine laboratory tests were unremarkable except a slight elevation of serum aminotransferase for the second patient. CSF evaluation showed mild proteinorachia in the first patient and pleiocytosis in the second. Extensive infectious work-­‐up was negative, except a positive Rhinovirus PCR on nasopharyngeal aspirate for to the first patient. Successive brain MRIs of the first patient demonstrated symmetric T2 hyperintensity in the thalami extending to the basal ganglia, infracortical white matter, cortex, and cerebellar peduncles. MRI of the second patient demonstrated asymmetric T2 hyperintensity in the insular cortex, the mesencephalon and the basal ganglia. Autoimmune, mitochondrial, organic acid and urea cycle disorders were excluded. NMDA receptor antibodies were absent. Genetic test for RANPB2 is pending. Brain biopsy in the second patient was not pathognomonic. Diagnosis of ANEC was evoked and corticosteroids were administred, followed by immunoglobulins and ultimately plasmapheresis. Clinical outcome was poor, with dystonic quadriplegia and dysautonomic disorder in both patients and additional parkinsonism in the second. Patients are currently severely disabled and necessitate gastrostomy feeding. Acute encephalopathy after viral illness is a severe condition requiring prompt management to improve neurological outcome. However, prognosis remains poor. The typical imaging features of ANEC will be developed in the poster. P113 -­‐ 2059 Recurrent acute disseminated encephalomyelitis in a child or multiple sclerosis? Bouchaala W, Chaari D, Jemaa R, Sakka S, Kammoun F, Triki C. Child neurology department, Hedi Chaker Hospital, Sfax, Tunisia -­‐ [email protected] Introduction: A number of clinical and para-­‐clinical data are similar between multiple sclerosis (MS) and acute dessiminated encephalomyelitis (ADEM), making difficult the distinguishing between these two diseases. The differentiation of these two conditions is still important both in diagnostic and therapeutic decision. Aim: Through the observation of a patient with recurrent neurological symptoms, we will try to find criteria to distinguish between these 2 entities. Case report: A 9 years old boy without any previous medical history presented at the age of 3 years an acutepost infectious cerebellar syndrome spontaneously regressive. MRI showed T2 signal hyperitensity lesion at the brain stem, basal ganglia, temporal lobes and external capsule. Four months later, he had presented an episod of hemiplegia and brain MRI showed new hypersignal in spinal cord extented to more two vertebers and in the cerebral white matter with regression of the lesions described above. The child received corticostroids in bolus. Actually, the patient had left hemiparesis and MRI showed disappearence of brain and spinal lesion with spinal atrophy at three months and 6 years later. The visual evoked potentials showed bilateral retrobulbar optic neuritis. Discussion: The differential diagnosis between MS and ADEM is more difficult in child then in adult. Although, some clinical and radiological criteria are predictive of ADEM: recent post infectious motor disorder, lesions with same age and some specific location as the brain stem, cortex, subcortical white matter and with favorable radiological evolution. In case of recurrent ADEM, clinical and radiological symptoms are located in the same territory then the first episode. The diagnosis of MS is suggested by the appearance of other lesion in different territory and the presence of infraclinical retrobulbar optic neuritis. P114 -­‐ 2049 Autoimmune limbic encephalitis and DRESS Syndrome: is there an association? Maras H, Ipekci B, Yologlu N, Aydogan M, Kara B. Kocaeli University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Kocaeli, Turkey -­‐ [email protected] Autoimmune encephalitis (AE) is characterised by intractable seizures, cognitive impairment and psychiatric symptoms. The non-­‐paraneoplastic causes may be associated with systemic autoimmune disorders, and autoantibodies to cell membrane or intracellular antigens. “Drug Rash with Eosinophilia and Systemic Symptoms” (DRESS) syndrome is a rarely seen drug related acute hypersensitivity reaction, and characterized by fever, lymphadenopathy, eosinophilia, and single or multi-­‐organ involvement. The pathogenesis of DRESS syndrome is not well known, but it is thought to be T lymphocyte mediated delayed hypersensitivity syndrome to toxic metabolites of drugs. Here, we report an 8-­‐year-­‐old boy developing DRESS syndrome after anti-­‐epileptic drug use during the course of AE. He presented with focal seizures and behavioral change. The initial diagnostic work-­‐up for encephalitis were negative. He was receiving phenytoin and clonazepam for intractable seizures. Three weeks after treatment, he developed DRESS syndrome. Antiepileptic drugs were stopped and steroid was started. He had no seizures during steroid treatment and psychiatric symptoms improved significantly. After steroid was withdrawn, his seizures and behavioural disorders restarted. After observing the clinical response to steroids during DRESS syndrome, AE was suspected and anti-­‐glutamic acid decarboxylase (GAD) antibody was 136 found to be high. Immunotherapy including intravenous immunoglobulin and methyl-­‐prednisolone was started with a good clinical response. During the course, tumour screenings were negative. It has been a year since the immunotherapy has started. He is seizure free for the last six months on clobasam and methyl-­‐prednisolone therapy. AE and DRESS syndrome are two different rarely seen autoimmune processes. We wanted to discuss the clinical significance of co-­‐existence of both diseases in our case. P115 -­‐ 2015 Preliminary data of national Romanian program of immunomodulatory treatment in children with multiple sclerosis Sandu C, Dica A, Butoianu N, Iliescu C, Tarta Arsene O, Cardas R, Craiu D, Burloiu C. Pediatric Neurology Department, Al. Obregia Clinical Hospital, Bucharest, Romania -­‐ [email protected] Introduction: Multiple Sclerosis (MS) is an immune mediated inflamatory disease occuring most commonly in young adults but is also diagnosed in children and adolescents. The majority of children with MS present a relapsing-­‐remitting form and the frequency of relapses is thought to correlate with disability on long term. There are recent studies considering initiation of early immunomodulatory therapy for reducing relapse rates and disease progression. Materials and methods: A National Health Program of immunomodulatory treatment in children with MS has been setup since 2010 and 15 adolescent patients have been included. All patients have been evaluated and diagnosed in our clinic using revised Mc Donald criteria. Age group varied between 13 and 17 years of age and females were predominant (9 adolescent girls). On inclusion, clinically isolated syndrome (CIS) was present in 8 patients and 7 patients exhibited relapsing remitting forms. The average duration from onset of disease until initiation of treatment was 17, 15 months.10 patients received Interferon –beta 1a and 5 patients received Interferon-­‐ beta 1b. Clinical features at onset of disease varied among patients. The EDSS score on inclusion was below 3 for all. There were 8 patients with 1 relapse before the initiation of treatment and 5 patients with relapses in the first year of treatment (only 10 patients with 1 year of treatment). The EDSS score on inclusion was below 3 for all patients. EDSS score was assessed for all patients after one year of treatment. Minor side effects were reported in most children at the initiation of treatment but no child discontinued treatment because of side effects. Conclusions: Further follow up will be needed and liaison with Adult Neurology Services in order to assess long term effectiveness and safety. P116-­‐ 1994 Subacute sclerosing panencephalitis presenting as schizophrenia and alpha coma pattern Ayse Kartal, Aysegul Nese Citak Kurt, Esra Gürkas, Kursad Aydin, Ayse Serdaroðlu. Dept.of Child Neurology, Inonu University Faculty of Medicine, Malatya, Turkey -­‐ [email protected] Introduction: Subacute sclerosing panencepahlitis (SSPE) is a progressive neurodegenerative disorder of the central nervous system caused by a persistent defective measles virus. The disease is characterized by cognitive detorioration, behavioural disturbances and myoclonic jerks. The diagnosis of SSPE is based on specific electroencephalographic abnormalities and elevated measles immunuglobulin G (IgG) in the cerebrospinal fluid. SSPE can have atypical electroencephalographic features at the onset.We describe the case of a 14 year old girl who presented with atypical clinical and electrographic features which is manifested 3 months of the diagnosis and treatment of a psychiatric disorder. Case: A 14-­‐year-­‐old girl was presented at the Pediatric Neurology Department with a four month history of deterioration in school performance, and behavioral changes mainly manifested by insomnia, visual, audiory hallucinations. She was evaluated by a psychiatrist and schizophrenia was considered. She treated with antipsychotic drugs, without any noticeable improvement her neurologic status for 3 months. Then she was referred to our department due to progressive cognitive detorioration and unsteady gait. There were no history of any myoclonic jerks and seizure. The patient was hospitalized to investigate the etiology of progressive cognitive detorioration. Initial electrogram showed diffuse back ground slowing, which evolved into frontally dominant alpha frequency waves without reactivity, suggestive of “alpha coma”. On the 3rd day of admission, generalized myoclonic jerks were developed and the alpha coma pattern was replaced by a characteristic intermittent background slowing along with presence of periodic paroxysmal sharp and slow wave discharges which did not disappear with diazepam infusion. SSPE was suspected, and CSF analysis was performed for measles. The cerebrospinal fluid measles immunoglobulin G titer was >1:1000.SSPE diagnosis is based on the clinical symptoms and EEG findings and isoprinosine therapy was started. In conclusion, SSPE can present initially with psychiatric symptoms and phsysicians, should be aware of this rare possibility. P117 -­‐ 1943 Response to rituximab in children with opsoclonus-­‐myoclonus syndrome resistant to conventional treatments 137 Mirabelli-­‐Badenier M, Fornarino S, Pisciotta L, Spinale B, Boeri L, Battaglia FM, Conte M, Battaglia T, Veneselli E, De Grandis E. DINOGMI Department-­‐University of Genoa, Child Neurology and Psychiatry Unit, Istituto G. Gaslini, Genoa, Italy -­‐ [email protected] Background: Immunosuppressive agents have been variably used over the years to treat childhood Opsoclonus-­‐
Myoclonus Syndrome (OMS). However, despite therapy, 70% of children have a chronic/relapsing clinical course with multiple neurological and developmental sequelae. Recently, multinational tasks forces proposed escalating treatments scheduling steroids pulses, intravenous immunoglobulins (IVIG), cyclophosphamide and rituximab, a CD20 monoclonal antibody. Objectives: to assess safety and efficacy of treatment with rituximab in resistant long-­‐ standing OMS forms as well as at earlier stages of disease. Materials and Methods: We report the long-­‐
term follow-­‐up (range 1-­‐4 years) after rituximab treatment of 5 OMS patients. Of these, 4 children showed chronic-­‐ relapsing course resistant to conventional therapies (steroids, ACTH and IVIG), while 1 child received early rituximab treatment after no benefit was reached with 7 steroid pulses. In all patients treatment response was recorded on the basis of an international score (the “OMS Severity Scale”) and the long-­‐term outcome was assessed by cognitive and neurological examination. Results: all patients underwent rapid and neurological improvement following rituximab administration; furthermore, no acute or late side effects were recorded during treatment. However, rituximab did not modify the cognitive impairment already present in long-­‐ standing forms. Conclusions: Our experience shows that rituximab represents a promising treatment for OMS and suggests that prompt treatment may be able to modify the clinical course of the disease. Rituximab, as a part of an escalating treatment strategy at earlier stages of disease, could protect against the irreversible cognitive and developmental deficits. Larger, controlled therapeutic trials are needed to confirm our results. P118 -­‐ 1929 Herpes simplex encephalitis: a diagnostic dilemma Voets S, Levy J, De Meirleir L. CHU Saint Pierre, Brussels, Belgium -­‐ [email protected] A 6 month-­‐old boy presented at the emergency room with a first episode of febrile generalized seizures. Consciousness was not altered. At the emergency ward (day 1) cerebrospinal fluid (CSF) exam was normal. The blood counts showed a mild infection. On day 3 after onset an EEG showed a lateralizing activity with generalized background slowing. A second CSF sample contained an elevated leukocyte count with predominance of neutrophils, pleocytosis and red blood cells but Herpes Simplex Virus (HSV)-­‐DNA by polymerase chain reaction or other viral and bacterial cultures were still undetectable. HSV serology in blood was negative. Based on the EEG and suspecting Herpes Simplex Encephalitis (HSE) acyclovir treatment was started. On day 4 the MRI showed important unilateral multicystic encephalomalacia in the right occipital lobe with expansion to temporal and parietal lobes. Clinically general physical and neurological symptoms improved. During hospitalisation (day 8) the patient had again fever on a nosocomial infection, but in the septic screening a third CSF exam was performed. All viral and bacterial cultures were negative, but HSV-­‐DNA by polymerase chain reaction was positive and confirmed the previous clinical diagnosis of HSE. Based on clinical findings, electroencephalographic changes and diagnostic imaging the patient was treated for 21 days. In conclusion, even when the CSF findings are normal, an HSV-­‐encephalitis should still be considered and treated based on the clinical, electroencephalographic changes and possible diagnostic imaging. P119 -­‐ 1890 Retrospective study to identify the viruses causing infections associated with febrile seizures Voets S, DeBacker P, Franck E, Levy J. CHU Saint Pierre, Brussels, Belgium -­‐ [email protected]­‐bru.be Every winter many infants and children are admitted to the emergency room for an acute seizure with fever, and the parent’s anxiety and remark -­‐“Why? Thought my child was dying!”-­‐ returns. We reassure the parents and treat the child, but most of the time we can’t clearly answer on the question of the parents. Febrile seizures are defined as seizures occurring in infancy or childhood, associated with fever but without evidence of intracranial infection, a previous afebrile seizure or other definable cause. It is usually accepted that that 2 to 5% of children will experience 1 or more febrile convulsions. The risk of febrile seizure is associated with many factors, including family history, and recent studies have identified gene loci associated with febrile seizures on chromosome 5, 8 and 19. These seizures are also age-­‐dependent with the median age of first presentation between 17 and 24 months, and even gender typed – more frequently in boys than in girls. With the diagnostic techniques, the importance of viral infections as the cause of the illnesses has been increasingly appreciated. However no recent study has comprehensively studied the viral etiology of the febrile episodes associated with febrile seizures. So we reviewed for this study all patients, admitted at the emergency room for febrile seizures from January till December 2012, to determine the causal virus of infection in the population of children found. And based on this information, we evaluated the specificity of certain viruses in the mechanism of the seizure: intensity of fever, 138 height of body temperature, possible pathology in developing more complex type febrile seizures then simple febrile seizures and to design certain EEG patterns following causal virus in febrile seizures. P120 -­‐ 1812 Amiodarone -­‐associated lumbosacral radiculoneuropathy and rhabdomyolysis in a child Kurian M, Dejeu Eric, Gauthey M, soroken C, Tissot-­‐daguette C, Truffert A, Korff C. Pediatric Neurology, University Hospital, Geneva, Switzerland -­‐ [email protected] Amiodarone toxicity has been reported in adults as a mixed polyneuropathy, vacuolar myopathy or both, in most cases after several months of treatment. We report the clinical, neurophysiologic findings and outcome of acute polyradiculoneuropathy and rhabdomyolyis in a child treated with amiodarone for atrial fibrillation. Case report: 14 year old girl of Senegalese origin, with severe mitral and tricuspid insufficiency and atrial fibrillation treated with amiodarone, introduced a week before surgery, presented on the fourth postoperative day,an abrupt onset of bilateral lower extremity tingling, numbness, pain and moderately severe asymmetric lower limb weakness. On examination, there was distal symmetric loss of sensibility of all modalities and absence of deep tendon reflexes in both lower limbs. Cerebrospinal fluid examination did not reveal albumino-­‐cytological dissociation. MRI of the lumbosacral region was normal. Electroneurography showed evidence of an axonal-­‐myelinic predominantly motor lumbosacral polyneuroradiculopathy. Serum creatine kinase levels were markedly elevated (10'206 U/l, normal values: 33-­‐187). She had a poor nutritional state (weight 29 kg). P121-­‐ 1764 Hypercytokines in cerebrospinal fluid from patients with encephalitis Chang YT, Chin ZN, Kuo HT, Chuang TY, Lin WD, Tsai CH, Chou IC. Division of Pediatrics Neurology, Children's Medical Center, China Medical University Hospital, Taichung, Taiwan -­‐ [email protected] Objectives: Without evidence of culture proved pathogens, the mechanism of encephalitis remains unclear. Hypercytokines in the brain, with subsequent brain edema and degenerative changes in the neural cell that may lead to poor prognosis. Here, we assessed the differences of cerebrospinal fluid (CSF) cytokine changes in patients with encephalitis between different outcomes. Materials and methods: Cytokine was analyzed using the Bio-­‐Plex Cytokine Assay System (Bio-­‐Rad Laboratories, Inc., San Diego, CA, USA). Interleukin (IL)-­‐1£], IL-­‐2, IL-­‐4, IL-­‐6, IL-­‐7, IL-­‐8, IL-­‐10, IL-­‐12, IL-­‐13, IL-­‐17, granulocyte colony-­‐stimulating factor, granulocyte¡V macrophage colony-­‐
stimulating factor and monocyte chemotactic protein-­‐1 (MCP-­‐1), interferon-­‐£^, macrophageinflammatory protein -­‐1-­‐alpha and tumor necrosis factor-­‐£\ were measured in 8 serial CSFs taken from 6 patients with encephalitis. Results: The outcome was poor in one patient and good in five patients. Hypercytokines in CSF were noted in IL-­‐6, IL-­‐8, and MCP-­‐1, which were 3810 pg/ml, 4475 pg/ml, and 1213 pg/ml, respectively. Extremely high level (three to four times above the average) was noted in patients with poor prognosis. Such high level cytokines persisted in serial taping with 24-­‐hour intervals. Conclusion: These finding suggesting that the accumulation of cytokines progresses in the central nervous system and results in a “cytokine storm” in the brain may lead to poor prognosis. However, the sample sized was small. Further study of prognostic value of CSF cytokines changes in encephalitis will be enrolled. P122 -­‐ 1750 Unusual clinical cases that mimic acute disseminated encephalomyelitis (ADEM) Duman O, Yurekli VA, Gencpinar P, Karaali K, Gumus H, Okuyaz C, Hazar V, Haspolat S. Department of Child Neurology, Faculty of Medicine, Akdeniz University, Antalya, Turkey -­‐ [email protected] Introduction: Acute disseminated encephalomyelitis (ADEM) is an immune-­‐mediated inflammatory demyelinating disorder of the central nervous system. Though most often observed as a single episode, relapsing or recurrent forms are also present. It can occur at any age, but it is predominantly a childhood disease. The diagnosis of ADEM is sometimes difficult, and depends on the exclusion of several other disorders. Herein, we reported six rare cases in whom clinical and radiological findings mimicked ADEM. Cases: Demographic characteristics, clinical and laboratory results of the patients were noted. Three of the patients (50%) had antecedent infections. Initial symptoms of the patients were as follows fever (50%), altered consciousness level (33.3%) and convulsions (16.7%). Upon neurologic examination, 83.3% of the patients were found to have long tract signs, 50% ataxia, 50% altered consciousness level and 33.3% hemiparesis. The final diagnoses were established by spinal MRI, by muscle biopsy and mitochondrial analysis, with clinical and laboratory findings, by bone marrow and spleen aspiration material examination and by brain biopsy from the lesional area in the cases. Final diagnoses were neuroblastoma, MELAS, CADASIL, Histiocytic sarcoma and Hemophagocytic syndrome. Conclusion: There is no simple test to secure diagnosis of ADEM, and its clinical presentation is polymorphic. Diagnosis depends on a synthesis of history, laboratory tests, neurological findings, treatment outcomes, and 139 exclusion of other diseases. Our case series has demonstrated the difficulties in diagnosing ADEM and has provided samples of extremely rare disorders that radiologically and clinically mimic ADEM. P123 -­‐ 1742 Extensive multifocal demyelinating encephalomyelitis with spectacular response to intravenous immunoglobulins Verhelst H, Maes M, Meersschaut V, Verloo P, Van Coster R. Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium -­‐ [email protected] In a few trials in adult patients with multiple sclerosis (MS) was shown earlier that the administration of intravenous immunoglobulins may be a safe and effective alternative for treatment of acute MS exacerbation, especially when steroids are contraindicated. In children, only a small number of case reports showed beneficial effect of intravenous immunoglobulins in refractory cases of acute demyelination. We report on a pediatric patient with steroid resistant extensive multifocal demyelinating encephalomyelitis who showed a spectacular positive response to the administration of intravenous immunoglobulins. Propositus was a previously healthy 9-­‐
year-­‐old boy who presented with unilateral progressive loss of vision followed by symptoms of encephalopathy (headache, vomiting), motor dysfunction and myelopathy (urinary incontinence). Three weeks earlier, he had signs of gastro-­‐enteritis. Ophthalmological examination revealed unilateral optic neuritis. MRI of the brain and spinal cord showed multiple, small, well-­‐defined juxtacortical lesions in cerebrum and cerebellum, in the capsula interna, pons, medulla oblongata and spinal cord. Some of the lesions showed gadolinium enhancement. The differential diagnosis was between acute disseminated encephalomyelitis (ADEM), MS or neuromyelitis optica. Steroid pulse therapy was started. Shortly therafter, headache and vomiting resolved and visual accuracy improved but motor problems and urinary incontinence worsened, and propositus became wheelchair bounded. Repeat MRI showed a marked increase in volume of existing lesions and an increase of the number of lesions. At that moment, an opportunistic infection was suspected although an infectious agent could not be demonstrated. Brain biopsy was performed revealing demyelinisation with infiltration of numerous lymphocytes and only limited signs of vasculitis consistent with the diagnosis of ADEM or MS. Therapy with intravenous immunoglobulins was started, 1g/kg/day for two days, with a remarkably positive effect. Symptoms started to improve after four days and completely resolved after one month. Also, subsequent MRI controls showed continued improvement of the lesions. P124 -­‐ 1723 Acute neurological disease associated with Mycoplasma pneumoniae infection Aguilera-­‐Albesa S, Zarikian-­‐Denis S, Moreno-­‐Galarraga L, Yoldi-­‐Petri ME, Durá-­‐Travé T, Herranz-­‐Aguirre M, Ocio-­‐
Ocio I, Díez-­‐Bayona V, Molina-­‐Garicano J. Paediatric Neurology, Navarra Hospital, Spain -­‐ [email protected] Objective: To describe the clinical characteristics, neuroimaging findings and outcome of 8 children with acute neurological disease associated with Mycoplasma pneumoniae (MP) infection. Material and methods: A retrospective review of 0-­‐15 year-­‐old patients with acute neurological manifestations, associated to positive serology in serum for MP. MP antibody titres over 1/160 were considered positive. Results: Mean age was 7 years (5-­‐12), 4 boys. They were diagnosed with: idiopathic intracranial hypertension (IH, cases 1,2,3); febrile epileptic status in a previously healthy 6-­‐yo boy (case 4); meningoencephalitis (case 5); opsoclonus-­‐ataxic syndrome after MP infection with occult neuroblastoma found after investigations (case 6); transverse myelitis (case 7); unilateral facial palsy (case 8). Five patients presented with previous respiratory infection. All showed positive MP antibody titres at neurological diagnosis (range 1/320-­‐ 1/20480). In cases 1-­‐7 lumbar puncture revealed 0-­‐640 predominantly polymorphonuclear cells. PCR for MP in CSF was normal in 3/3. CNS MRI showed transient abnormal findings in 4/7: white matter right temporal T2 hyperintensity (case 3); ADEM-­‐like pattern with basal ganglia T2+FLAIR asymmetric hyperintesities (case 4); selective symmetric basal ganglia hyperintensities (case 5); and transverse myelitis (case 7). EEG showed transient left frontotemporal slow-­‐waves in cases 4-­‐5. All patients received clarithromycine. Corticosteroids were used in cases 3,5,6,7 and immunoglobulins in cases 5-­‐6 with significant clinical and neuroimaging improvement in all cases. Case 3 suffered a clinical relapse of IH with MP 1/640 titres one year after being asymptomatic with negative MP. In case 6 paravertebral neuroblastoma was removed but she required prolonged immunosuppressive treatment. Discussion: Acute neurological disease associated with MP is usually monophasic but also could be recurrent. MP may acts as a trigger for underlying pathology. Respiratory infection symptoms are not always present, and CSF studies can be normal. A causal relationship between MP and acute neurological manifestations remains to be elucidated. 140 P125 -­‐ 1700 MRI pattern recognition for congenital CMV Aleksanyan A, Yepiskoposian M. Arabkir Joint Medical Center, Yerevan, Armenia -­‐ [email protected] Introduction: This report describes a case in which MRI pictures lead to diagnosis of Congenital CMV. Case presentation: 2 months old infant was hospitalized because of diffuse skin lesions. He is 1st child from 1st pregnancy, child was born at term, with low birth weight.He had microcephaly, severe spasticity, high tendon reflexes, restriction of hip abduction and he was underweight. Bilateral sensorineural hearing loss was revealed by audiometry and hepatic cyst was found by ultrasonography. MRI was done and diffuse white matter changes, bilateral temporal cysts, abnormal gyration, intraventricular septae were found in it. It was suspested CMV and then it was confirmed by PCR in dry blood of Gurthrie card taken for screening purposes. Conclusion: The presence of the described MRI findings is an indication for CMV investigation. And MRI with such changes can be pattern recognition for Congenital CMV. P126 -­‐ 1693 Paediatric sciatic neuropathy presenting as painful leg: a case report and review of literature Iqbal M, Prasad M, Babiker M, Ritey C. Sheffield Childrens Hospital, Sheffield, UK -­‐ [email protected] Introduction: Mononeuropathies in general are very uncommon in childhood. Sciatic neuropathy (SN) is probably underappreciated in childhood and likely to represent nearly one quarter of childhood mononeuropathies. Method: We present a 7 old girl who presented with painful right lower limb and abnormal gait. Detailed investigation revealed transient eosinophilia, abnormal neurophysiology and MRI suggestive of isolated sciatic neuropathy. Result: She has responded very well to physiotherapy and has made a complete motor recovery although she is left with an area of abnormal sensation affecting the lateral border of her right leg and the dorsum of her foot. Discussion: Differential diagnoses for paediatric SN will be discussed including compressive neuropathies in children and various hyper-­‐eosinophilia syndromes. Compressive neuropathies in childhood are very rare and compression of the sciatic nerve is the second most common group after peroneal nerve lesion. P127 -­‐ 1650 Severe PANDAS-­‐like course: a case report Cindro Heberle L, Pavlović M, Neubauer D, Al Tawari A. Al Sabah Hosp., Ped. Dpt., Kuwait -­‐ [email protected] Objective: clinical spectrum of autoimmune disorders following infection with group A beta-­‐hemolytic streptococcus may extend beyond Syndenham chorea and PANDAS. We report a boy with life-­‐threatening course improved after immunotherapy. Case presentation: 11 years old boy with 1 year long history of facial tics developed fever with throat infection progressing to lethargy and epileptic status stopped by anticonvulsants but severe agitation, fidgetting and frequent tics were observed afterwards, soon to be followed by another epileptic status and central apneas requiring intubation and intensive care for several days. Virology work up and CSF study were normal, high titers of ASOT ( 3200 IU/ml) were found. EEG detected slow background activity, on MRI brain subtle thalamic changes were seen. Treated by antibiotics, immunoglobulins, methyl-­‐prednisolone and antiepileptics the child gradually improved but cognitive impairment (IQ 68 ), depressive behavior, tics and occasional focal seizures have remained. Conclusions: we believe that the boy had an extremely severe form of PANDAS-­‐like condition finally leading to residual epilepsy, cognitive deficits and depression. P128 -­‐ 1627 Overview of pediatric peripheral facial nerve paralysis: analysis of 40 patients Ozkale Y, Erol I, Saygi S, Yýlmaz I. Baskent University Faculty of Medicine, Department of Pediatrics, Adana Teaching and Medical Research Center, Turkey -­‐ [email protected] Objectives: Peripheral facial nerve paralysis (PFNP) in children might be alarming sign of serious disease such as malignancy, systemic disease, congenital anomalies, trauma, infection, middle ear surgery and hypertension. It may also be caused due to immunization and toxic factors or Bell’s palsy. Therefore, careful investigation and differental diagnosis are essential in children. Materials and Methods: The cases of 40 consecutive children, and adolescents who diagnosed as PFNP at Baskent University Adana Hospital Pediatrics and Pediatric Neurology Unit between January 2010 and January 2013 were retrospectively evaluated. Results: There were 15 boys and 25 girls, age range, 2 months to 17 years (with a median age, 6.5 ± 4.51 years). All of the patients had acquired, first episode and unilateral PFNP. As regards the etiology of PFNP in children, we determined the most common cause was Bell’s palsy (26 cases, 65%), fallowed by infection (11 cases, 37,5%), tumor lesion (1 case, 2,5%), suspected chemotheraphy toxicty (1 case 2,5%). In the infectious group; 5 patients with PFNP had otitis media from clinical examination. Seven children had serological evidence of specific triggers: Borellia Burgdorferi (3); herpes simplex virus (3), mycoplasma (1). Thirty one patients with facial nerve paralysis were treated with oral 141 steriods. We also didn’t reveal a significant difference in the outcome of facial nerve paralysis between treated and not treated groups. We noted that younger patients had generally poor outcome than older patients with regardless of disease etiology. Conclusion: PFNP has been reported in many countries from America and Europe, however, knowledge about its clinical features, microbiology, neuroimaging, and treatment in Turkey is incomplete. Present study demonstrated that Bell’s palsy, infection and trauma were the most most common etiologies of PFNP in Southern coast of Anatolia (Mediterranean region). P129 -­‐ 1592 Isolated sphenoid sinusitis masquerading migraine Jeong-­‐Ho L, Eun Sook, S. Department of Pediatrics, College of medicine, Soonchunhyang University Hospital, Seoul, Korea -­‐ [email protected] Objective: Sinusitis is a well-­‐known cause of headache, with an incidence of around 9% among children and adolescents. But, isolated sphenoid sinusitis is a rare disease and its symptoms are often non-­‐specific and confusing. So the diagnosis can be difficult to differentiate from migraine headache. But there are few reports of isolated sphenoid sinusitis and headaches in children. Results: Case 1: A 10-­‐year-­‐old boy was referred for evaluation of migraine headaches. Headache with diplopia started 6 months ago. His headaches were located at both parietal area associated with photophobia, lasting 1-­‐2 hours. Events were occurred nearly every day, occasionally relieved by sleep. He was afebrile without evidence of nasal congestion or facial tenderness over his sinuses. His neurologic and ophthalmologic examinations were normal. The brain magnetic resonance (MRI) showed isolated Right sphenoid sinusitis. After oral antibiotic treatment for 3 weeks, his symptoms were relieved and follow up MRI showed improved sinusitis. Case 2: A 8-­‐year-­‐old female presented with a 2 weeks history of severe headache with dizziness, nausea. Her mother has the migraine history. She denied any nasal symptoms or fever. The headaches were described as both sided, constant and throbbling, exacerbated with head movement, lasting 1 hour. Her neurologic examination was normal and no tenderness on sinuses area. MRI was requested to rule out intracranial pathology and revealed isolated sphenoid sinusitis. After one month oral medication, her headaches were relieved. Conclusion: Two children who presented for suspected migraine headaches had isolated sphenoid sinusitis. P130-­‐ 1577 A case of brain abscess arising from sinusitis Lee BL. Department of Pediatrics, Pusan Paik Hospital, Inje University College of Medicine, Busan, Korea -­‐ [email protected] Introduction: Brain abscess is regarded as a significant intracranial complication of bacterial sinusitis. We report a case of cerebritis proceeded by acute sinusitis which progressed into a large abscess in spite of adequate empirical antibiotic therapy and sinus drainage. Cases: A 13-­‐year-­‐old girl was admitted to our hospital with pyrexia and headache. She had past history of chronic sinusitis. On examination, she had neck stiffness, but there was no focal neurologic deficit. Laboratory findings revealed a neutrophilia. Computed tomography of the brain identified a sphenoid sinusitis, but there was no other abnormal finding. A spinal tap showed normal cerebrospinal fluid. Empirical antibiotic therapy with cefotaxime was initiated. However, fever and headache were aggravated. Brain magnetic resonance imaging (MRI) performed on five days after admission revealed cerebritis of right frontal lobe, small abscess formation (< 1 cm) in connection with anterior skull base wall and ethmoid and sphenoid sinusitis. Vancomycin and metronidazole were empirically added, and functional endoscopic sinus surgery (FESS) was done for sinus drainage. Bacterial culture from drainage presented Staphylococcus aures. However, in spite of appropriate antibiotic therapy and FESS, her fever and headache appeared again after two weeks. Follow-­‐up MRI showed enlarged rim enhancing lesion in right frontal lobe with central cystic necrosis (about 4.4 x 2.5 cm). A prompt neurosurgical bur hole aspiration was performed. Postoperatively, her symptoms were improved and intravenous antibiotics were continued for 6 weeks. MRI performed four weeks after operation showed a nearly improving state of abscess. No recurrence was noted during the 6-­‐month follow-­‐up period, and she remained free of neurologic deficit. Conclusion: Intracranial complication secondary to sinusitis can be progressed to be potentially life threatening despite the appropriate use of broad-­‐spectrum antibiotics. Therefore, a high degree of suspicion, along with serial neuroimaging and prompt neurosurgical intervention, is required. 142 P131 -­‐ 1553 Acute cerebellitis presenting with sudden onset headache accompanied by elevated CSF IgG Index Lee KY. Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Korea -­‐ [email protected] Acute cerebellitis, a rare inflammatory syndrome of the cerebellum, is one of the important causes of acute cerebellar dysfunction in childhood. Although it typically presents with cerebellar dysfunction such as ataxia, non-­‐localizing symptoms such as headache can be much more prominent than cerebellar symptoms because of increased

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