Spasticity - Utah Physical Therapy Association

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SPASTICITY
MECHANISMS AND
MANAGEMENT
Allison Oki, MD
October 11, 2014
Objectives







Video – Development/Basic Mechanics of Gait
Overview Motor Disorders, Hypertonia, Spasticity
Pathophysiology
Cerebral Palsy
UMN syndrome - Consequences of Spasticity
Medical Management
Neurosurgical Interventions: ITB and SDR
Development



Bipeds center of mass
(COM) level of S2
Inherently unstable
Continual postural
adjustment to maintain
COM within base of
support




Sit 6 mo
Crawl 9 mo
Independent walking
12 mo
Gait maturation at 6.5
years
Motor System



Motor system
hierarchical
chain of command
extends from the
cortical centers down
to the nerves that
innervate the muscles
Components of Motor System






Supplementary motor
cortex
Cortical motor control
centers
Basal Ganglia
Cerebellum
Brainstem Motor nuclei
Central pattern
Generators
Motor Pyramid
Pyramidal and Extrapyramidal
Upper Motor Neurons
Pyramidal
direct corticospinal tract
 Fine coordination motion
Extrapyramidal
indirect cortco-bulbo-spinal
tracts (vestibular/ reticular
tracts)
 Balance, posture,
coordination
Central Pattern Generators



Located in the SC generate
a consistent specific
movement pattern
Analogy – piano key and
note, central pattern
generator when stimulated
produces the same
movement pattern
Anterior horn of SC


Pyramidal – lateral
Extrapyramidal - medial
Motor Disorders

Disorders of multiple neural components
 basal
ganglia
 cerebellum
 cerebral cortex
 brainstem
 descending spinal tracts

Hypertonia is a component of many motor disorders
 Spasticity,
dystonia and rigidity
Motor Disorders
Pyramidal
 cortical projections to the
brainstem (corticobulbar)
 SC (corticospinal)
clinically: weakness and
increased stretch reflexes
“pyramidal”
“upper motor neuron”
weakness
Extra-pyramidal
 Injury to BG, cerebellum or
non-primary motor cortical
areas
clinically: abnormal motor
control without weakness or
changes in spinal reflexes
What is spasticity?
“Spasticity is a motor disorder characterized by a velocity
dependent increase in tonic stretch reflexes, with exaggerated
tendon jerks resulting from hyperexcitability of the stretch
reflex, as one component of the upper motor neuron
syndrome” Lance 1980
 Resistance to stretch increases with increasing speed and varies
with the direction of the joint movement
 Rapid rise in resistance to stretch above a threshold speed or
joint angle
Sanger et al, Classification and Definition of Disorders Causing Hypertonia in Childhood, Pediatrics 2003
Hypothetical Mechanism
Pathophysiology of Spasticity
Theories

Imbalance between excitatory and inhibitory impulses to the alpha
motor neuron in the spinal cord

Due to a loss of descending inhibitory input to the alpha motor
neuron due to injury to the cortical spinal tracts
Descending
Inhibition
Sensory
Excitation
Cerebral Palsy: Definition



Primary abnormality of movement and posture
secondary to a nonprogressive lesion of a
developing brain
Represents a group of disorders rather than a
single entity
Abnormal motor control and tone in the absence of
underlying progressive disease
Epidemiology CP




Most common motor
disorder of childhood
3.6/1000 school age
children
Higher survival rate of
premature infants
Etiology – majority of term
infants do not have an
identifiable cause


Causative factors
 Prematurity
 Infection
 Inflammation
 Coagulopathy
Greatest RF prematurity
<37wks

Incidence highest in the very
premature
Pathology CP





>80% abnormal
neuroimaging
PVL – white matter near
the lateral ventricles
Premature 90% vs term
20%
IVH
Corticospinal tract fibers to
LE are medial to UE →
spastic diparesis
Common Gait Deviations CP
Location
Impairment
Potential Effects
Hip
↑ adductor tone
Scissoring, difficulty advancing leg in
swing
↑ iliopsoas tone
Anterior pelvic tilt, lumbar lordosis,
crouched gait
↑ femoral anteversion
Intoeing, false genuvalgus, compensatory
external tibial torsion
Abductor weakness
Trendelenberg gait
↓ hamstring ROM
Crouched gait
Hamstring/Quad co-contraction
Stiff-kneed gait
↑ gastroc tone/contracture
Toe walking, genu recurvatum, difficulty
clearing foot during swing
Internal tibial torsion
Intoeing, ineffective toe-off
External tibial torsion
Out-toeing, ineffective toe-off
Varus
↑ supination in stance or swing
Valgus
↑ pronation in stance or swing, midfoot
breakdown
Knee
Ankle
Upper Motor Neuron Syndrome UMNS
Positive





Spasticity
Spastic Dystonia
Clonus/ hyper-reflexia
Reflex flexor and extensor
spasms
Associated reactions
Negative






Weakness
Fatigue
Loss of selective motor
control
Sensory deficits
Incoordination
Poor balance
Allison Brashear, Spasticity and Other Forms of Muscle Overactivity in the Upper Motor Neuron Syndrome,
Nathaniel H. Mayer, Ch.1 Positive Signs and Consequences of an Upper Motor Neuron Syndrome, 2008
David Scrutton et al, Management of the Motor
Disorders of Children with Cerebral Palsy, H. Kerr
Graham, Ch.8 Mechanisms of Deformity
UMNS
UMNS disability =
positive + negative + rheologic properties
Rheologic properties: viscoelastic properties of the muscle and
other soft tissues
 Structural changes occur in the muscle cells causing intrinsic
muscle stiffness (Olsen et al. 2006)
Combined effects of all signs → chronic unidirectional postures
and movements that are generated by a net balance of muscle
torques exerted across the involved joints
Allison Brashear, Spasticity and Other Forms of Muscle Overactivity in the Upper Motor Neuron Syndrome,
Nathaniel H. Mayer, Ch.1 Positive Signs and Consequences of an Upper Motor Neuron Syndrome, 2008
UMNS
Torque – force generated by muscle acting through a bony lever
arm →rotational movement
Normal movement is bi- or multi-directional, agonist and
antagonist torques create motion
 UMNS → net unidirectional movements (positive signs) often
persist as postures because voluntary bi- or multi-directional
movement is impaired (negative signs) → chronic effects on
soft tissue, joint structures and bone
Allison Brashear, Spasticity and Other Forms of Muscle Overactivity in the Upper Motor Neuron
Syndrome, Nathaniel H. Mayer, Ch.1 Positive Signs and Consequences of an Upper Motor Neuron
Syndrome, 2008
Why is spasticity important?



Clinically diagnosed and
treated
Musculoskeletal and
neurologic exam
 Tone, reflexes, strength,
coordination
Spasticity →
significant disability

ADLs

Seating

Comfort

Contracture

Loss of ROM

Negative impact on function

Bone deformity

Pain

Skin

Hygiene

Ability to provide cares
Allison Brashear, Elie Elovic, Spasticity Diagnosis and Management, 2010, Ch 1.1 Why is spasticity important?
Secondary effects of Spasticity
May effect function and long-term outcome
 Persistent muscle imbalance → muscle/tendon contractures →
joint or bone deformities
 weak antagonists muscles → require passive stretch for a
minimum of 6 out of 24 hrs to maintain muscle length (Tardieu
1988) and to avoid development of a fixed contracture
(Eames 1999)
Abnormal forces across joints → prolonged abnormal posture,
increase energy expenditure, impair function, and negatively
affect both the caregiver’s and patient’s QOL
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake
Forest University Press, p.40
Abnormal Forces across Joints


Ankle and subtalar → fixed equinus, equinovarus or
equinovalgus hindfoot deformities
Adductor and iliospoas spasticity → hip subluxation and
dislocation


Once a critical degree (50%) of hip subluxation is present,
dislocation is inevitable unless intervention occurs (Reimers 1987)
The resultant pelvic obliquity compromises sitting balance →
chronic pain
L. Andrew Koman, et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest
University Press
Bone Deformity
Abnormal muscle forces act on a growing skeleton
 Hips and spine → essential in weight bearing
and positioning
 Femur → muscle and gravity loading forces
during growth
 Muscle forces in CP → increased anteversion
of femoral neck
 hip flexion, adduction and internal rotation of
the femur → femoral head in a
superoposterolateral direction, out of the
acetabulum → coxa valgus: deformation of the
femoral head and shallow acetabulum
Randall L. Braddom, Physical Medicine and Rehabilitation,
3rd Edition, Chapter 54: Cerebral Palsy, p.1249
Hip Dysplasia
Hip Subluxation
James R. Gage et al, The Identification and Treatment of Gait Problems in Cerebral Palsy, 2009, Kevin Walker,
Chapter 3.4 Radiographic Evaluation of the Patient with Cerebral Palsy
Bone Deformity
Asymmetric muscle pull → deformity of the spine
 Kyphosis, scoliosis, rotational deformities






Comfort
Tone
Sitting
Standing alignment
Balance
Severe → respiratory function compromise
Randall L. Braddom, Physical Medicine and Rehabilitation, 3rd Edition, Chapter
54: Cerebral Palsy, p.1249
Goals of Spasticity Management









Decrease spasticity
Improve functional ability and independence
Decrease pain associated with spasticity
Prevent or decrease incidence of contractures
Prevent bony deformity
Improve ambulation, mobility, function
Facilitate hygiene
Ease rehabilitation procedures
Improve ease of caregiving
Traditional Step-Ladder Approach
to Management of Spasticity
Neurosurgical procedures
Orthopedic procedures
Neurolysis
Oral medications
Rehabilitation Therapy
Remove noxious stimuli
Interdisciplinary team








Patient and family
Neurologist
Neurosurgeon
Occupational therapist
Physical Therapist
Physiatrist
Orthopedic Surgeon
Primary care physician
Rehabilitation Therapy





Stretching
Weight bearing
Inhibitory casting
Bracing
Strengthening



EMG biofeedback
Electrical stimulation
Positioning
Oral Pharmacologic Management
Baclofen
 Diazepam
 Clonidine
 Tizanidine
 Dantrolene Sodium

Allison Brashear, Elie Elovic, Spasticity Diagnosis and Treatment, 2010, Ch.15 Pharmacologic Management
of Spasticity: Oral Medications
Systemic medications: limitations






Sedation
Hypotension
Confusion
Weakness
Nausea
For generalized rather than focal spasticity
Baclofen – GABA analog


Binds to presynaptic
GABA-B receptors in the
brainstem, dorsal horn of
SC and other CNS sites
Depresses both
monosynaptic and
polysynaptic reflexes by
blocking the release of NTS


Inhibition of gamma motor
neuron activity to the
muscle spindle
Because these reflexes
facilitate spastic
hypertonia, inhibition
reduces the overactive
reflex response to muscle
stretching or cutaneous
stimulation
Baclofen



Dystonia
Baclofen some supraspinal
activity that may contribute
to clinical side effects
Orally – relatively low
concentrations in CSF
Side Effects
 Central SE – drowsiness,
confusion, attentional
disturbances
 Others – hallucinations,
ataxia, lethargy, sedation
and memory impairment
 Lower seizure threshold
 Sudden withdrawal →
seizures, hallucinations
Baclofen
Pharmokinetics
 Relatively well absorbed,
peak effect 2 hrs, t ½ 2.54 hours
 Excreted unchanged by
kidney, 6-15%
metabolized in the liver
 Schedule 3x a day due to
short half life
Considerations:
 Cerebral lesions more
prone to SE
 DOC for spinal causes
Diazepam - Benzodiazepine





MOA: does not directly
bind to GABA receptors
Promotes the release of
GABA from GABA-A
neurons
Enhanced pre-synaptic
inhibition, likely why useful
in epilepsy
All CNS depressants
Anti-anxiety, hypnotic, antispasticity and anti-epileptic
Side Effects:
 Sedation and lethargy
 Impair coordination and
prolonged use can lead to
physical/psych dependence
 Effective doses vary
considerably, upper doses
primarily limited by SE
 Rapid withdrawal →
irritability, tremors, nausea
and seizures
Neuromuscular Blockade
Goal: Restore balance between agonist and antagonist muscles
Why is this important?
 Shortened over contracted muscles → decreased muscle growth despite
linear bone growth → antagonist muscles become over-lengthened →
weakness and imbalance
 Contractures → bone and joint deformity → impaired function
 Early intervention – life long patterns of mobility
 Blockade of agonist muscles → improved stretch, ROM, increased resting
length, antagonist muscles can continue activity and strengthening
Ann H. Tilton, Injectable Neuromuscular blockade in the treatment of Spasticity and Movement
disorders, Journal of Child Neurology, 2003:18:S50-66
Botulinum Toxin A in the management of
spasticity related to CP
BTX-A is currently used for children of all ages with CP
for spasticity management as determined by the
practitioner
 This use is off-label in the US
 Dysport (British formulation), approved in UK and EU
for “treatment of dynamic equinus foot deformity due
to spasticity in ambulant pediatric CP patients, two
years of age or older…UE spasticity post-stroke,
spasmodic torticollis, blepharospasm, and hemifacial
spasm”
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake
Forest University Press
Neuromuscular Junction
NMJ – connection between the
peripheral nerve and muscle
fibers
 Signals from the motor neuron
are transmitted by the release
of Ach from presynaptic
vesicles
 Ach crosses the synaptic cleft
and attaches to post-synaptic
receptors → muscle contraction
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002,
Wake Forest University Press
Neuromuscular Junction
Chemodenervation, The Role of Chemodenervation in the Management of Hyperkinetic Movement Disorders,
We Move 2007
Selected Literature Review
1990 several studies supported the safety and efficacy of
therapeutic BTX in children with CP
 Goals: decreasing spastic equinus, improving crouch knee gait,
decreasing hip flexion, improving hand use
 Studies demonstrated changes in muscle tone (reduction in
spasticity scores), improvements in ROM, and kinematic
changes in gait analysis
 However, functional benefit was not demonstrated in blind,
randomized controlled trials
 2013 Systematic review of interventions for children with CP:
state of the evidence – BTX was recommended for spasticity
reduction and improved walking
Iona Novak et Al, A systematic Review of interventions for children with cerebral palsy: state of the evidence, Developmental Medicine & Child
Neurology, 2013
Selected Literature Review
Why is it so difficult to show functional benefit?
 Weakness and poor coordination co-exist in persons with
spasticity, perhaps reducing muscle overactivity is not sufficient
to see a functional change in the absence of a robust posttreatment program
 Variability in injection protocols
 patient selection
 Insensitive outcome measures
 Individualized treatment
Geoffrey L. Sheean, Botulinum treatment of Spasticity: Why is it so difficult to show a
functional benefit?, Current Opinion in Neurology, 2001, 14: 771-776
BoNT
Indications
 Dynamic deformity –
function, pain, progressive
deformity
 Equinus, crouch gait, pelvic
obliquity
 UE
 Focal dystonia
 Muscle imbalance
 Sialhorrhea
Contraindications
 Allergic rxn to toxin or
vehicle
 Resistance to toxin effects
 Significant muscle
weakness
 Failure to respond to
injections
 Fixed contracture
Side Effects






Most common weakness
Hoarseness or trouble
talking
Dysarthria
Loss of bladder control
Trouble breathing
Trouble swallowing
FDA warning label and risk
mitigation strategy 2009
Advise patients to seek
immediate medical
attention if they develop
any of these symptoms
Equinus
Gastrocnemius
Soleus
Posterior tibialis
Phenol Injections



Injections of phenol were used for several decades
prior to the advent of BoNT-A
Chemical neurolysis – phenol injected onto a motor
nerve denervating that particular muscle
EMG stimulus to localize the target nerve
Can be injected into:
Motor points: Motor neurons within a muscle
Motor nerves: before they innervate a muscle
Phenol Injections




Localization of the motor neuron needs to be
precise. Time required depends on which and how
many nerves are injected
Typically requires multiple needle placements and
burns with injection – anesthesia in sensory aware/
cognitively aware child
Dosing guidelines not well established in peds
<30mg/kg considered safe
Phenol Injections
Adverse Effects
 Dysesthesias most common
 Typically occur if phenol injected into a sensory
nerve, can result in burning sensation or
hypersensitivity to touch that can last for several
weeks
 Ibuprofen, gabapentin or carbamazapine
Phenol Injections
Duration of action
 3-12 months, can be longer than 1 yr
 Increased duration typically occurs in muscles with
more accessible nerves
 Obturator - hip adductors
 Musculocutaneous nerve - biceps
 motor points within the medial hamstrings are more
difficult to find
Discussion
Both BoNT and phenol cause selective and temporary muscular
denervation
 Treatment for focal spasticity
 Different mechanisms of action
 Phenol has proven effectiveness, immediate onset, low cost and
potentially longer duration of effects, but generally less
popular than BoNT
 Technical challenges with administration, concerns for safety
and adverse effects
Summary
Intramuscular injection of BTX-A well tolerated and efficacious balance muscle forces across joints
Pre-defining injection goals, appropriate patient selection, and
monitoring are essential
 equinus deformity, managing selected upper limb deformities,
adjunct in the global management of spasticity
 Decrease pain related to spasticity, care-giver burden and
enhance health-related quality of life
 treatment philosophy includes early use in appropriate
patients, to avoid contracture, delay/prevent bone and joint
abnormalities, and avoid corrective surgery.
Goals of ITB Therapy




Reduce
spasticity
Decrease pain
associated
with spasticity
Improve function
Facilitate care
Intrathecal Baclofen vs Oral
ITB
 CSF acts at GABAB
receptor sites at spinal
cord
 Lower doses than
required daily
 Fewer side effects
Oral baclofen
 Low blood/brain
barrier penetration,
high systemic
absorption and low
CNS absorption
 Lack of preferential
SC distribution
 Unacceptable SE at
effective doses
Plasma vs CSF drug levels
Plasma
CSF
Plasma (est)
Penn RD, Kroin JS. Intrathecal baclofen in the long-term management of
severe spasticity. Neurosurg. 1989; 4(2): 325-332.
CSF
Intrathecal Delivery
Advantages
 Higher concentration
of drug in CSF
 Decreased SE
 Titrateable
Disadvantages
 Invasive
 Risk of infection
 Surgical risk
 Devise risk
 Maintenance
 Cost
Intrathecal Baclofen Therapy



Baclofen directly to CSF
target neurons in the SC
Externally
programmable,
surgically implanted
pump, drug delivered at
precise flow rates via
catheter placed in the
spinal canal
Decreases hypertonicity
CP, SCI, MS, Strole
trauma or hypoxia
Neurophysiologic effects





Dose dependent decrease in
spinal reflex response
Disappearance of tendon taps
and decrease in severity of
spasms
Biomechanical and
neurophysiologic studies –
evidence of decreased resistance
to imposed stretch, decrease in
EMG response
At neuronal level – baclofen acts
as potent GABA-B receptor
agonist
GABA-B extensively distributed
in SC

Baclofen directly administered to
the subarachnoid space –
enhanced access to receptors →
greater reflex inhibition and tone
reduction
Intrathecal Baclofen
Patient Selection



Grahm HK, Aoki KR, et al, Gait and Posture, vol II, 2000:6769
Grid illustration to compare
various therapies for spasticity
ITB – reversible (neural
structures are not surgically
altered, dose rate adjustable)
and global
Pts with global or multifocal
spasticity, who may benefit from
adjustable (vs permanent)
clinical effects are generally
considered as better candidates
Components of ITB Therapy




Accessible drug reservoir
Catheter that connects drug
reservoir to the CSF
Programmable – adjustable for
independent patient needs and
response
External programming device
Synergistic Therapeutic effects



ITB combined with other
modalities for synergist
therapeutic effect
Rehabilitative therapies, oral
pharmacotherapy, neurolytic
procedures and muscle tendon
lengthening
Combining ITB with neurolytic
procedure –focal dystonic
features and global
hypertonicity or residual UE
hypertonia


Orthopedic procedures and ITB –
correction of fixed deformities in
the setting of ongoing spastic
hypertonia
Concomitant use – in children
with CP may reduce the need for
subsequent orthopedic surgery
Gertzen et al, Intrathecal baclofen infusion and
subsequent orthopedic surgery in patients with
Cerebral Palsy. J Neurosurg 1998;88:1009-13
Pump Placement
Ambulatory Function
1.
2.
3.
CNS injury or disease, will ITB
administration permit
ambulation or improve
ambulation?
Pts able to walk with assistance,
will ITB improve their walking
ability or allow them to walk
independently
For pts who are able to walk,
will they experience decline of
walking ability after ITB?



Isolated case reports of regained
ability to walk
Prognosis for improving
ambulatory function favors those
with better baseline function
Most larger studies report mixed
results, some pts improving,
smaller percentage significantly
worsening, with the largest
subgroup non-significant changes
overall
Withdrawal
Abrupt cessation → withdrawal,
serious and potentially fatal
 “itchy, twitchy, bitchy”
 Pruritus, seizures, hallucinations,
autonomic dysreflexia
 Exaggerated rebound spasticity,
fever, hemodynamic instability
and AMS
 Can progress over 24-72 hrs to
rhabdomyolysis (CK and
phosphokinase), elevated
transaminase levels, hepatic and
renal failure and rarely death
Treatment:
 Supportive care
 Observation and replacement of
baclofen either enteral, or
preferably through restoration of
intrathecal delivery
 Oral baclofen 10 -20 mg PO Q
4-6 hrs prn,
 Tranxene 3.75 1-2 tabs mg Q4
 Alternating every 2 hrs
ITB Therapy




ITB therapy has become a mainstay of long term
spasticity management
Benefits include more potent effects, fewer systemic
side effects, titratable
Disadvantages – cost, maintenance, requires
vigilance, risk of malfunction of catheter pump
system, withdrawal and overdose, surgical risks
Appropriate patient selection and education are
critical
SDR: The Basics



First performed in 1913, but did not become
popular until 1970’s
Dorsal rhizotomy became selective and outcomes
evaluated since 1987
SDR involves cutting sensory nerve roots that when
stimulated, trigger exaggerated motor responses as
measured by EMG intraoperatively
The Procedure





Multilevel laminectomy vs. minimally invasive
approaches
L1 – S1 sensory roots are identified and divided
into 3-5 rootlets
Each rootlet is stimulated and responses are
measured via EMG
Rootlets with the most abnormal signal are cut
Surgery takes about 4 hours
Potential Complications





Paralysis of legs
Neurogenic bladder
Sensory loss or dysethesias
Wound infection
CSF leak
SDR: Outcomes of Metanalysis


Children with diplegic CP (GMFCS II-III) received
SDR + PT, or PT w/o SDR.
Concluded that SDR + PT is efficacious in
reducing spasticity and has a small effect on
gross motor function
McLaughlin J et al. Dev Med Child Neuro 2002, 44: 17-25.
SDR versus ITB



1-year outcomes of 71 children who underwent SDR before 1997
versus 71 children with ITB, matched by GMFCS and age
Both interventions significantly decreased Ashworth scores, increased
PROM, improved function and resulted in high parental satisfaction
Compared with ITB
 SDR provided greater improvements in muscle tone, PROM, and
gross motor function
 Fewer patients in the SDR group required subsequent orthopedic
procedures
 No difference between the degree of parents’ satisfaction
Kan P et al. Childs Nerv Syst. 2007 Sep 5.
Outcomes
Short and long term outcomes demonstrate:
 Decreased spasticity
 Improved or unchanged strength
 Improved gait pattern
 Decreased oxygen cost
 Improved overall function including decreased use
of walking aids
Candidacy Determinations






Pre-term birth
Imaging consistent with PVL
Primarily spastic tone
Evidence of fair selective motor control
Demonstrated ability to cooperate and follow
through with rehabilitation program
Patient selection
Candidacy Determinations

Red flags






Hyperextension at the knee in gait
Multiple orthopedic procedures
Generalized lower extremity/trunk weakness
Poor incorporation of trunk in gait
Poor isolated control of lower extremity movement
Poor rehab potential (behavior, sensory issues,
cognition, social)
Summary





Spasticity: Abnormal, velocity dependent increase in resistance
to passive movement of peripheral joints due to increased
muscle activity
Spasticity is a type of hypertonia that is a component of the
UMNS
Due to a loss of presynaptic inhibition - modulation of the
afferent stimulus by the descending tracts
Positive and negative signs of the UMNS collectively cause net
unidirectional movements that often persist as postures →
chronic effects on soft tissue, joint structures and bone
Spasticity contributes to significant disability
Summary


CP – spasticity is a common clinical feature associated with
PVL
Traditional step ladder approach to management: therapies,
oral medications, injection therapies, orthopedic procedures,
ITB or SDR, patient/family goals
Thank you
References
Sanger et al, Classification and Definition of Disorders Causing Hypertonia in Childhood, Pediatrics
2003
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002,
Wake Forest University Press
James R. Gage et al, The Identification and Treatment of Gait Problems in Cerebral Palsy, 2009,
Warwick J. Peacock, Chapter 2.2 Pathophysiology of Spasticity
David Scrutton et al, Management of the Motor Disorders of Children with Cerebral Palsy, H. Kerr
Graham, Ch.8 Mechanisms of Deformity
Allison Brashear, Spasticity and Other Forms of Muscle Overactivity in the Upper Motor Neuron
Syndrome, Nathaniel H. Mayer, Ch.1 Positive Signs and Consequences of an Upper Motor
Neuron Syndrome, 2008
Randall L. Braddom, Physical Medicine and Rehabilitation, 3rd Edition, Chapter 54: Cerebral Palsy,
p.1249
James R. Gage et al, The Identification and Treatment of Gait Problems in Cerebral Palsy, 2009,
Kevin Walker, Chapter 3.4 Radiographic Evaluation of the Patient with Cerebral Palsy
References Continued
MC Olsen et al, Fiber type-specific increase in passive muscle tension in spinal cord injured
subjects with spasticity, Journal of Physiology, 577:339-52, 2006
Allison Brashear, Elie Elovic, Spasticity Diagnosis and Management, 2010, Ch 1.1 Why is
spasticity important?
Allison Brashear, Elie Elovic, Spasticity Diagnosis and Treatment, 2010, Ch.15 Pharmacologic
Management of Spasticity: Oral Medications
R. Zafonte et al, Acute care management of post-TBI spasticity, Journal of Head trauma
Rehabilitation 19(2):89-100
Stretch Reflex Pathway
1.
2.
3.
4.
5.
Muscle spindle stretch
receptor detects changes
in muscle length
Myelinated sensory
afferent neuron
The synapse
Homonymous motor neuron
Muscle innervated by the
motor neuron
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University
Press
Stretch Reflex Pathway
Stretch detected by the muscle spindle
→ CNS by Ia afferents through
the dorsal root, connections in the
SC:

Homonymouos motor neuron
monsynaptic excitatory connection
with alpha motor neuron

Heteronymous motor neuron
monosynaptic excitatory
connections to synergist

Ia inhibitory interneuron projects
to alpha motor neurons of
antagonist muscles
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University
Press
Stretch Reflexes
Reciprocal inhibition – normal pattern
simultaneous excitation of agonist
and inhibition of antagonist motor
neuron
Co-contraction – inappropriate
activation of antagonist muscles
during voluntary contraction of
agonist muscles, superimposed
stretch reflex activity – stretching
antagonists during movement
 joint stability (ie eccentric contraction
of the triceps during biceps
activation to control flexion of the
elbow)
 Activated and deactivated at the
cortical level
 May represent an impairment of
supraspinal control of reciprocal
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management
of Cerebral Palsy, 2002, Wake Forest University
inhibition
Press
Traditional Step-Ladder Approach
to Management of Spasticity
Neurosurgical procedures
Orthopedic procedures
Neurolysis/ Chemodenervation
Oral medications
Rehabilitation Therapy
Remove noxious stimuli
Common Patterns of Motor Dysfunction in CP
Most common pattern of spasticity in CP:
Upper Extremity
 Internal rotation of shoulder
 Elbow flexion
 Forearm pronation
 Wrist and finger flexion
 Thumb in palm
Lower Extremity
 Hip flexion and adduction
 Knee flexion
 Hindfoot valgus
 Forefoot pronation
Spasticity Associated with CP in Children, Guidelines for the use of Botulinum
Toxin A, L. Andrew Koman et al, Pediatric Drugs, 2003, 5 (1) p.11-23
Windswept Deformity
Possible Advantages of Spasticity




Maintains muscle tone
Helps support circulatory function
May prevent formation of deep vein thrombosis
May assist in function
Diazepam - Benzodiazepine





MOA: does not directly
bind to GABA receptors
Promotes the release of
GABA from GABA-A
neurons
Enhanced pre-synaptic
inhibition, likely why useful
in epilepsy
All CNS depressants
Anti-anxiety, hypnotic, antispasticity and anti-epileptic
Side Effects:
 Sedation and lethargy
 Impair coordination and
prolonged use can lead to
physical/psych dependence
 Effective doses vary
considerably, upper doses
primarily limited by SE
 Rapid withdrawal →
irritability, tremors, nausea
and seizures
Clonidine
Central Alpha Adrenergic Agent
Monoamines are widely
distributed in CNS
 Important role as
modulators of spinal neuron
excitability
 Modulate sensory inputs via
presynaptic inhibition of
spinal afferent inputs
 Also direct inhibitory effect
on interneurons

When descending
pathways from the
brainstem to SC are
disrupted, there is a
reduction in the NE →
increased hypertonia
Clonidine
Central Alpha Adrenergic Agent




Centrally acting apha-2
receptor agonist →
antispasticity effects
Also alpha-1 receptor
agonist → antihypertensive
effects
profound nociceptive pain
reliever
central sympatholytic
effects on BP

Therefore little effect on
the BP of persons with
complete SCI, but can lower
the BP for those with
incomplete injuries
Side Effects
 BP
 Bradycardia, dry mouth,
ankle edema, depression
Tizanidine – Central Selective Alpha-2
adrenergic agonist




Structurally related to
clonidine
1/10 to 1/15 the potency
of clonidine in lowering BP
or slowing HR
Preference for alpha-2
receptors
Active at both segmental
spinal and supraspinal
levels in both motor and
sensory pathways



No effect on monosynaptic
reflexes – standard DTR
No activity at NMJ, no
direct effect on skeletal
muscle fibers, does not
cause any muscle weakness
Extensive first pass
metabolism
Tizanidine – Central Selective Alpha-2
adrenergic agonist
Side Effects:
 Sedation, asthenia,
dizziness, dry mouth
 Very little hypotension or
bradycardia at clinically
relevant doses, virtually
none in the lower half of
the dose range
 Rebound HTN
 Hallucinations and
nightmares
 GI - constipation
Precautions
 Chronic use – potential for
hepatotoxicity
 Liver enzymes should be
periodically checked as
dose is increased
Dantrolene Sodium
Direct Acting Muscle Relaxant



No centrally acting SE
Acts peripherally by
decreasing release of
calcium from SR→
uncoupling electrical
excitation from contraction
and decreasing the force
of contraction
Affects intrafusal and
extrafusal fibers, reducing
spindle sensitivity


Action is specific for
skeletal muscle and affects
reflex contractions or
spasticity more than
voluntary contraction
Weakness -twice the
voluntary effort is required
to maintain a desired
muscle tension
Dantrolene Sodium
Direct Acting Muscle Relaxant



Because of propensity to cause weakness several reports
advocate limiting use in CP, spasticity of spinal origin and MS
pts
1980 AMA “Dantrolene should be used primarily in nonambulatory pts and only if the resultant decrease in spasticity
will not prevent the patient from functioning”
Recent report has recommended as a first line agent in the
treatment of spasticity after TBI, especially in the acute setting,
as it exhibits minimal cognitive effects and may not interfere
with neural recovery
R. Zafonte et al, Acute care management of post-TBI spasticity, Journal of Head
trauma Rehabilitation 19(2):89-100
Dantrolene Sodium
Direct Acting Muscle Relaxant
Risks:
 Significant increased risk of hepatotoxicity, 1%
overall, especially with doses over 400mg
 Active hepatic diagnosis contraindication
 RF: female, >35, polypharmacy
 LFTs need to be monitored, lowest optimally
effective dose should be prescribed
History of Botulinum Toxin A
1875 – Claude Bernard – “poisons can
be employed as means for the
destruction of life or as agents for
the treatment of the sick”
This concept was first used regarding CP
in the 20th century
 Tardieu – Alcohol as a muscular
neurolytic agent, 1970s
 Carpenter (Richmond CP Hospital) –
45% alcohol and bupivicaine
1897 van Ermengem (Belgium) identifies
Clostridium botulinum, obligate
anaerobe bacillus
WWII - Schantz – extensive research
identifies the toxins produced by C.
botulinum
 7 serotypes purified and identified
(A-G)
 Emphasis on type A, the most potent
biologic toxin known
Techniques developed by Schantz and
Lammana → commercial
preparations available today
 Lamanna – produced crystalline
BTX-A, forerunner of Oculinum
 British military → British formulation
BTX-A, Dysport
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002,
Wake Forest University Press
History of Botulinum Toxin A
1960s – Alan B. Scott, Opthalmologist in SF,
toxin as therapeutic agent for strabismus
1981 – BTX-A in humans

dystonia and other movement disorders

Schantz type A toxin, Oculinum used in
these protocols under the oversight of the
FDA
1988 – Koman et al, first clinical trial for
treatment of spasticity in CP

Oculinum, preliminary results 1993

Subsequent trials, including large multicenter placebo controlled trials →
efficacy of BTX-A for managing equinus
foot deformity (Koman 2000)
Since then – BoNT → safe and effective for a
large number of neurologic and nonneurologic diseases
regarding CP, additional studies confirmed
indication for:

UE CP (Corry 1997, Fehlings 2000)

Analgesia after hip surgery (Barwood
2000)

Crouched gait (Molanaers 1999)

Alternative to serial casting (Corry 1998)

Hamstring spasticity (Corry 1999)
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake
Forest University Press
History of Botulinum Toxin A
1989 – Allergan purchases the Oculinum
in stock and the process to produce
new bulk source of toxin from Dr.
Scott
 FDA approves BTX-A for strabismus,
blepharospasm, and hemi-facial
spasm (>12)
1992 – registers tradename BOTOX
2000 – BTX-A and B
(Myobloc/Neurobloc, Solstice) FDA
approval for dystonia
2002 – FDA approval for cosmetic use
2004 – FDA approval for hyperhidrosis
2010 – approval for UE spasticity in
Adults
 Acceptance for treatment of
spasticity is growing, with approvals
in many European countries
 Continued clinical trials for
expanding indications
L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake
Forest University Press
Summary
Intramuscular injection of BTX-A is well tolerated and efficacious
if used to balance muscle forces across joints in the absence of
fixed contractures
 Pre-defining injection goals, appropriate patient selection, and
monitoring are essential
 It is well documented as a treatment option for equinus
deformity, managing selected upper limb deformities, and is
valuable as an adjunct in the global management of spasticity
 It can diminish pain related to spasticity, decrease care-giver
burden and enhance health-related quality of life
 treatment philosophy includes early use in appropriate
patients, to avoid contracture, delay/prevent bone and joint
abnormalities, and avoid corrective surgery.
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