Evaluating an apparent unprovoked first seizure in adults

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Practice Parameter: Evaluating
an apparent unprovoked first
seizure in adults (an evidencebased review)
Report of the Quality Standards Subcommittee
of the American Academy of Neurology and
the American Epilepsy Society
A. Krumholz, S. Wiebe, G. Gronseth, S. Shinnar, P. Levisohn,
T. Ting, J. Hopp, P. Shafer, H. Morris, L. Seiden, G. Barkley, and J.
French
© 2009 American Academy of Neurology
The AAN develops these presentation
slides as educational tools for
neurologists and other health care
practitioners. You may download and
retain a single copy for your personal use.
Please contact [email protected] to
learn about options for sharing this
content beyond your personal use.
© 2009 American Academy of Neurology
Presentation Objectives
• To review the evidence regarding
evaluation of a first nonfebrile seizure in
adults
-
Only apparent unprovoked first seizure considered
Patients with epilepsy per se excluded
Epilepsy definition used requires recurrent (two or more)
unprovoked seizures1
First seizure defined using the International League Against
Epilepsy criteria
• To present evidence-based
recommendations
© 2009 American Academy of Neurology
Overview
•
•
•
•
Background
Gaps in care
AAN guideline process
Analysis of evidence, conclusions,
recommendations
• Recommendations for future research
© 2009 American Academy of Neurology
Background
• Annually approximately 150,000 adults will present with a first
seizure in the United States.2
• It is estimated that 40% to 50% of these incident seizures recur to
be classified as epilepsy, a condition of recurrent, unprovoked
seizures.2,3
• The lifetime cumulative risk of developing recurrent unprovoked
seizures or epilepsy by the age of 80 years ranges from 1.4% to
3.3%.2
• Even one seizure is a frightening, traumatic event with serious
potential consequences, such as loss of driving privileges,
limitations for employment, and bodily injury.
• One major study estimates the annual cost of epilepsy in the United
States at $12.5 billion in 1995.4
© 2009 American Academy of Neurology
Gaps in Care
• Misdiagnosis may lead to ineffective management choices5,6 and
excessive and unnecessary costs.4
• Errors in diagnosis, seizure classification, and prognosis are known
to lead to inappropriate decisions on the use or choice of
antiepileptic drugs and to other serious patient management
errors.5,6
• A single seizure can be the first manifestation of epilepsy or may be
a symptom of a brain tumor, a systemic disorder, an infection, or a
syndrome that deserves special attention and treatment.1,7,8
© 2009 American Academy of Neurology
Gaps in Care, cont.
• Studies of individuals presenting with presumed new onset seizures
report that about 50% of these individuals, after careful history and
questioning, actually have had previous seizures and merit a
diagnosis of epilepsy.9
• Although the recurrence rates differ in individuals after a first seizure
as opposed to a new diagnosis of epilepsy, both patient groups are
at significant risk for seizure recurrence.3
© 2009 American Academy of Neurology
AAN Guideline Process
Clinical Question
Evidence
Conclusions
Recommendations
© 2009 American Academy of Neurology
Clinical Questions
• The first step in developing guidelines is to
clearly formulate questions to be answered.
• Questions address areas of controversy,
confusion, or variation in practice.
• Questions must be answerable with data
from the literature.
• Answering the question must have the
potential to improve care/patient outcomes.
© 2009 American Academy of Neurology
Literature Search/Review
Rigorous, Comprehensive, Transparent
Complete
Search
Review abstracts
Review full text
Select articles
Relevant
© 2009 American Academy of Neurology
AAN Classification of Evidence
• All studies rated Class I, II, III, or IV
• Five different classification systems:
– Therapeutic
• Randomization, control, blinding
– Diagnostic
• Comparison to gold standard
– Prognostic
– Screening
– Causation
© 2009 American Academy of Neurology
AAN Level of Recommendations
• A = Established as effective, ineffective, or harmful (or
established as useful/predictive or not useful/predictive)
for the given condition in the specified population.
• B = Probably effective, ineffective, or harmful (or
probably useful/predictive or not useful/predictive) for the
given condition in the specified population.
• C = Possibly effective, ineffective, or harmful (or
possibly useful/predictive or not useful/predictive) for the
given condition in the specified population.
• U = Data inadequate or conflicting; given current
knowledge, treatment (test, predictor) is unproven.
Note that recommendations can be positive or negative.
© 2009 American Academy of Neurology
Translating Class to
Recommendations
• A = Requires at least two consistent Class
I studies.*
• B = Requires at least one Class I study or
at least two consistent Class II studies.
• C = Requires at least one Class II study or
two consistent Class III studies.
• U = Studies not meeting criteria for
Class I through Class III.
© 2009 American Academy of Neurology
Translating Class to
Recommendations, cont.
* In exceptional cases, one convincing
Class I study may suffice for an “A”
recommendation if 1) all criteria are met,
2) the magnitude of effect is large (relative
rate improved outcome >5 and the lower
limit of the confidence interval is >2).
© 2009 American Academy of Neurology
Applying This Process
to the Issue
We will now turn our attention to the
guidelines.
© 2009 American Academy of Neurology
Clinical Questions
1. Should an EEG be routinely ordered in an adult
presenting with an apparent unprovoked first
seizure?
2. Should a brain imaging study (CT or MRI) be
routinely ordered in an adult presenting with an
apparent unprovoked first seizure?
3. Should blood counts, blood glucose, and
electrolyte panels be routinely ordered in an
adult with an apparent unprovoked first seizure?
© 2009 American Academy of Neurology
Clinical Questions, cont.
4. Should a lumbar puncture be routinely
performed in an adult presenting with an
apparent unprovoked first seizure?
5. Should toxicologic screening be routinely
ordered in an adult presenting with an apparent
unprovoked first seizure?
© 2009 American Academy of Neurology
Methods
• MEDLINE, CINAHL, and the Cochrane
Trials Register
– 1966 to November 2004 (with manual
searches through February 2008)
– Relevant, fully published, peer-reviewed
articles
© 2009 American Academy of Neurology
Methods
• Search terms/phrases
–
–
–
–
first seizure
first presentation
new diagnosis of seizure
new diagnosis of epilepsy
© 2009 American Academy of Neurology
Methods, cont.
• Two panelists reviewed each article for
inclusion.
• Risk of bias was determined using the
classification of evidence for each study
(Classes I–IV).
• Strength of practice recommendations was
linked directly to levels of evidence (Levels A, B,
C, and U).
• Conflicts of interest were disclosed.
© 2009 American Academy of Neurology
Literature Review
190 abstracts
53 articles
© 2009 American Academy of Neurology
Inclusion criteria:
- Relevant to the clinical
questions
- Limited to human
subjects
- Articles identified by
panel members
Exclusion criteria:
- Studies primarily on
established/chronic
epilepsy patients or acute
provoked seizures
- Pharmacodynamic/
pharmacokinetic studies
- Letters/case reports
AAN Classification of Evidence
for Screening
• Class I: A statistical, population-based sample of
patients studied at a uniform point in time (usually early)
during the course of the condition. All patients undergo
the intervention of interest. The outcome, if not objective,
is determined in an evaluation that is masked to the
patients’ clinical presentations.
• Class II: A statistical, non-referral-clinic-based sample of
patients studied at a uniform point in time (usually early)
during the course of the condition. Most patients undergo
the intervention of interest. The outcome, if not objective,
is determined in an evaluation that is masked to the
patients’ clinical presentations.
© 2009 American Academy of Neurology
AAN Classification of Evidence
for Screening, cont.
• Class III: A sample of patients studied during the course
of the condition. Some patients undergo the intervention
of interest. The outcome, if not objective, is determined
in an evaluation by someone other than the treating
physician.
• Class IV: Expert opinion, case reports, or any study not
meeting criteria for Class I to III.
© 2009 American Academy of Neurology
Analysis of Evidence
Question 1: Should an EEG be routinely
ordered in an adult presenting with an
apparent unprovoked first seizure?
© 2009 American Academy of Neurology
Conclusion and Recommendation
• Conclusion: For adults presenting with an apparent
unprovoked first seizure, analysis of the evidence from 1
Class I and 10 Class II studies indicates that the EEG is
probably helpful. It has a substantial yield with about
29% of EEGs demonstrating significant abnormalities10,11
and these abnormalities predict the risk for seizure
recurrence.
• Recommendation: The EEG (routine) should be
considered as part of the neurodiagnostic evaluation of
the adult with an apparent unprovoked first seizure
because it has a substantial yield (Level B).8,10,11
© 2009 American Academy of Neurology
Conclusion and Recommendation
• Conclusion: In addition, EEG is regarded as a standard
for the initial classification of seizures since it forms a
basis for the “clinical and electroencephalographic
classification of epileptic seizures.”10,11
• Recommendation: The EEG (routine) should be
considered as part of the neurodiagnostic evaluation of
the adult with an apparent unprovoked first seizure
because it has value in determining the risk for seizure
recurrence (Level B).
© 2009 American Academy of Neurology
Analysis of Evidence
Question 2: Should a brain imaging
study (CT or MRI) be routinely ordered
in an adult presenting with an apparent
unprovoked first seizure?
© 2009 American Academy of Neurology
Conclusion and Recommendation
• Conclusion: For adults presenting initially with an
apparent unprovoked first seizure, the evidence from
seven Class II studies indicates that a brain imaging
study, either a CT or MRI, is probably useful. It has a
significant yield of about 10%, which may lead to the
diagnosis of disorders such as a brain tumor, stroke,
cysticercosis, or other structural lesions, and may have
some value in determining the risk for seizure
recurrence.
• Recommendation: Brain imaging using CT or MRI
should be considered as part of the neurodiagnostic
evaluation of adults presenting with an apparent
unprovoked first seizure (Level B).
© 2009 American Academy of Neurology
Analysis of Evidence
Question 3: Should blood counts,
blood glucose, and electrolyte panels
be routinely ordered in an adult with an
apparent unprovoked first seizure?
© 2009 American Academy of Neurology
Conclusion
• Conclusion: Data from two Class II and four Class III
studies showed that in adults presenting with an
apparent unprovoked first seizure, although some
abnormal laboratory results are reported, there is not
sufficient evidence to support or refute recommending
routine testing of blood glucose, blood counts, or
electrolyte panels. The necessity for such studies should
be guided by specific clinical circumstances based on
the history, physical, and neurologic examination.
© 2009 American Academy of Neurology
Recommendation
• Recommendation: In the adult initially presenting with
an apparent unprovoked first seizure, blood glucose,
blood counts, and electrolyte panels (particularly sodium)
may be helpful in specific clinical circumstances, but
there are insufficient data to support or refute routine
recommendation of any of these laboratory tests (Level
U).
© 2009 American Academy of Neurology
Analysis of Evidence
Question 4: Should a lumbar puncture
be routinely performed in an adult
presenting with an apparent
unprovoked first seizure?
© 2009 American Academy of Neurology
Conclusion
• Conclusion: Data from two Class III studies revealed
significant abnormalities in up to 8% of a mixed group of
patients presenting to an emergency department with a
first seizure. However, the studies selectively performed
lumbar punctures based on clinical findings and included
patients who did not meet our inclusion criteria, such as
those with acute symptomatic causes for their seizures
or who had not returned to their normal baseline
function.
© 2009 American Academy of Neurology
Recommendation
• Recommendation: In the adult initially presenting with
an apparent unprovoked first seizure, lumbar puncture
may be helpful in specific clinical circumstances, such as
patients who are febrile, but there are insufficient data to
support or refute recommending routine lumbar puncture
(Level U).
© 2009 American Academy of Neurology
Analysis of Evidence
Question 5: Should toxicologic
screening be routinely ordered in an
adult presenting with an apparent
unprovoked first seizure?
© 2009 American Academy of Neurology
Conclusion and Recommendation
• Conclusion: In two Class III studies considering the
value of toxicology screening in adult patients presenting
with a seizure, some patients with apparent unprovoked
first seizure were included, but neither study investigated
the use of routine toxicology screening for such patients.
• Recommendation: In the adult presenting with an
apparent unprovoked seizure, toxicology screening may
be helpful in specific clinical circumstances, but there are
insufficient data to support or refute a routine
recommendation for toxicology screening (Level U).
© 2009 American Academy of Neurology
Future Research
•
•
The history, physical, and neurologic examinations form the basis for the
diagnosis and classification of epileptic seizures,11 and this is acknowledged
by expert consensus.11 Still, future research is warranted to determine the
specific aspects of the history, physical, and neurologic examination that are
most useful in both initial diagnosis of a seizure and subsequent
management.
Also, it would be helpful to understand how this type of information should
best guide performance and timing of other neurodiagnostic or laboratory
studies. An international group recently recommended a broader definition
of epilepsy as a brain disorder with a history of at least one seizure and
“characterized by an enduring predisposition to generate epileptic
seizures.”8 This type of approach will require validation and investigation,
including determination of the true value of diagnostic studies such as EEG
in establishing the presence of an epileptic syndrome after a first seizure. In
regard to the EEG, one limitation of currently available studies is the
variability in the timing of the EEG after incident seizure.
© 2009 American Academy of Neurology
Future Research, cont.
•
•
•
•
•
There is some evidence in children that an EEG done within 24 hours of a
presenting seizure gives a higher yield of significant abnormalities.12 In
regard to the EEG, one limitation of currently available studies is the
variability in the timing of the EEG after incident seizure.
Although all types of seizures are considered in this analysis, most patients
had a convulsive seizure. This may be because convulsive seizures are
more likely to prompt acute medical attention than a simple or complex
partial seizure. More studies specifically focusing attention on all types of
initial seizures, not just convulsive seizures, are needed.
Other factors deserve consideration in future investigations. For instance,
the costs of these various tests do not receive much attention in studies of
patients with first seizure and should. Also, the elderly are a growing
proportion of the general population and warrant special consideration in
future investigations.
Another unresolved issue relates to the need for immediate hospitalization
of patients with a first seizure. Some guidelines exist, but well designed
studies are needed.7
© 2009 American Academy of Neurology
Future Research, cont.
•
•
Prediction of seizure recurrence after a first unprovoked seizure is important
to guide decisions regarding antiepileptic drug therapy, patient
management, and counseling. Many factors are reported to predict seizure
recurrence including the etiology of the seizures and association with
neurologic abnormalities.3
Although the EEG and brain imaging studies are reported to predict seizure
recurrence, studies vary in support of that observation and in respect to the
specific EEG abnormalities or brain imaging findings that are most
significant. Some of this variability regarding EEG findings may relate to the
timing of the study after the initial event and to the decision whether to treat
with antiepileptic medications. The value of specific findings on the EEG,
brain imaging, and other variables deserve further study in regard to seizure
recurrence risks. Also, future studies of the clinical utility for such
neurodiagnostic procedures should employ standardized tests and
prediction algorithms.13
© 2009 American Academy of Neurology
Future Research, cont.
•
•
Future studies are needed to analyze the value of expert input into the
history, physical, neurologic examination, or diagnostic testing such as the
EEG or brain imaging. The expertise and qualifications of individuals
interpreting such information or tests particularly the EEG or brain imaging
vary considerably and may influence interpretations and outcomes.13 These
are not simple “positive” or “negative” tests, like a pregnancy test; they
require expertise for proper interpretation.
Some other diagnostic studies deserve further analysis in patients
presenting with new onset seizures. In particular, routine electrolytes
including serum sodium and glucose were reported in some studies to be of
value, but this was not consistent or confirmed by other reports. Also,
toxicologic screening was reported as important in some limited series, but
was not studied in a manner to allow adequate evidence-based verification
or refutation of its routine utility.
© 2009 American Academy of Neurology
Future Research, cont.
•
•
Studies of patient management and counseling at the time of first diagnosis
of a single seizure or epilepsy are recommended. For example, which
patients should receive antiepileptic drug treatment, and, if so, exactly what
type and when should they get it? Also, when is the patient best advised
regarding driving laws and other social issues, and how and by whom
should this be done? This is not a trivial issue. For instance, a British study
noted that only 21% of all adult first seizure patients received the correct
advice about driving limitations.14
We recommend that future studies address the issues that we raise here.
To best determine how to optimally evaluate the adult presenting with a first
seizure, those studies should be structured to emphasize the use of large,
well-characterized samples, clearly defined subjects and outcomes, and
standardized data collection methods.
© 2009 American Academy of Neurology
Outline for Seizure Assessment:
Features of a Seizure*
• Associated factors
– Age
– Medical history – previous history of similar episodes, prior stroke, brain
tumor, systemic illness, mental illness, drug or alcohol abuse
– Family history
– Developmental status
– Behavior
– Health at seizure onset – febrile, ill, exposed to illness, complaints of not
feeling well, sleep deprived
– Precipitating events other than illness – trauma, alcohol, medications,
illicit drugs, toxins
*Adapted from Hirtz et al.12
© 2009 American Academy of Neurology
Outline for Seizure Assessment:
Features of a Seizure*, cont.
• Symptoms during seizure (ictal)
–
–
–
–
–
Aura: Subjective sensations
Behavior: Mood or behavioral changes before the seizure
Preictal symptoms: Described by patient or witnessed
Vocal: Cry or gasp, slurring of words, garbled speech
Motor: Head or eye turning, eye deviation, posturing, jerking (rhythmic),
stiffening, automatisms (purposeless repetitive movements such as
picking at clothing, lip smacking); generalized or focal movements
– Respiration: Change in breathing pattern, cessation of breathing,
cyanosis
– Autonomic: Pupillary dilation, drooling, change in respiratory or heart
rate, incontinence, pallor, vomiting
– Loss of consciousness or inability to understand or speak
*Adapted from Hirtz et al.12
© 2009 American Academy of Neurology
Outline for Seizure Assessment:
Features of a Seizure*, cont.
• Symptoms following a seizure (postictal)
–
–
–
–
–
–
–
–
Amnesia for events
Confusion
Lethargy
Sleepiness
Headaches and muscle aches
Transient focal weakness (Todd’s paresis)
Nausea or vomiting
Biting of tongue
*Adapted from Hirtz et al.12
© 2009 American Academy of Neurology
References
1.
2.
3.
4.
5.
6.
7.
Commission on Epidemiology and Prognosis, International League Against
Epilepsy. Guidelines for epidemiological studies on epilepsy. Epilepsia
1993;34:592–596.
Hauser WA, Hesdorffer DC. Epilepsy: frequency, causes, and consequences. New
York: Demos Publications; 1990.
Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked
seizure: a quantitative review. Neurology 1991;41:965–972.
Begley CE, Famulari M, Annegers JF, et al. The cost of epilepsy in the United
States: an estimate from population-based and survey data. Epilepsia 2000;41:
342–352.
Grunewald RA, Chroni E, Panayiotopoulos CP. Delayed diagnosis of juvenile
myoclonic epilepsy. J Neurol Neurosurg Psychiatry 1992;55:497–499.
Krumholz A. Nonepileptic seizures: diagnosis and management. Neurology
1999;S76–83.
American College of Emergency Physicians (ACEP) Clinical Policies Committee and
the Clinical Policies Subcommittee on Seizures. Clinical Policy: Critical issues in the
evaluation of adult patients presenting to an emergency department with seizures.
Ann Emerg Med 2004;43:605–625 .
© 2009 American Academy of Neurology
References, cont.
8.
9.
10.
11.
12.
13.
Fisher RS, Boas WvE, Blume W, et al. Epileptic seizures and epilepsy: Definitions
proposed by the International League Against Epilepsy (ILAE) and the International
Bureau for Epilepsy (IBE). Epilepsia 2005;46:470–472 .
Jallon P, Loiseau P, Loiseau J. Newly diagnosed unprovoked epileptic seizures:
Presentation at diagnosis in CORALE study. Epilepsia 2001;42:464–475.
Commission on Classification and Terminology of the International League Against
Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes.
Epilepsia 1989;30:389–399.
Commission on Classification and Terminology of the International League Against
Epilepsy. Proposal for revised clinical and electroencephalographic classification of
epileptic seizures. Epilepsia 1981;22:489–501.
Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile
seizure in children. Neurology 2000;55:616–623.
Gilbert DL, Sethuraman G, Kotagal U, Buncher R. Meta-analysis of EEG test
performance shows wide variation among studies. Neurology 2002;60:564–570.
© 2009 American Academy of Neurology
References, cont.
14. Edmondstone WM. How do we manage the first seizure in adults? J R Coll Phys
Lond 1995;29:289–294.
For a complete list of references, please access
the full guideline at www.aan.com/guidelines
© 2009 American Academy of Neurology
Questions/Comments
© 2009 American Academy of Neurology
Thank you for your
participation!
© 2009 American Academy of Neurology

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