Faculty Bibliography

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient care based on analysis of evidence. For this practice parameter the authors reviewed available evidence relevant to evaluating adults presenting with an apparent unprovoked first seizure. METHODS: Relevant questions were defined and addressed by multiple searches of medical literature. Each article was then reviewed, abstracted, and classified using an established evidence scoring system. Conclusions and recommendations were based on a standard three-tiered scheme of evidence classification. RESULTS: For adults presenting with a first seizure, a routine EEG revealed epileptiform abnormalities in approximately 23% of patients, and these were predictive of seizure recurrence. A brain imaging study (CT or MRI) was significantly abnormal in 10% of patients, indicating a possible seizure etiology. Laboratory tests such as blood counts, blood glucose, and electrolyte panels were abnormal in up to 15% of individuals, but abnormalities were minor and did not cause the seizure. Overt clinical signs of infection such as fever typically predicted significant CSF abnormalities on lumbar puncture. Toxicology screening studies were limited, but report some positive tests. Recommendations: EEG should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Brain imaging with CT or MRI should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Laboratory tests, such as blood counts, blood glucose, and electrolyte panels (particularly sodium), lumbar puncture, and toxicology screening may be helpful as determined by the specific clinical circumstances based on the history, physical, and neurologic examination, but there are insufficient data to support or refute recommending any of these tests for the routine evaluation of adults presenting with an apparent first unprovoked seizure (Level U)

The design of clinical trials can be explained in terms of selection of a control group. Two options have included (a) using an active comparator, usually a standard drug such as carbamazepine (active control) or (b) using a placebo or low-dose control. Because neither active control nor placebo/dose control appeared to be acceptable alternatives for monotherapy studies in epilepsy, a new concept has been considered: the use of 'historical control'. This method uses the 'expected' (imputed) behavior of placebo, based on prior trials. Some trials have been performed in patients with refractory epilepsy, who are withdrawn from their previous antiepileptic drugs, and converted to monotherapy on a study drug, using a low-dose comparator, frequently called 'pseudo-placebo.' A meta-analysis of all pseudo-placebo arms was performed to determine whether they could serve as a historical control for future monotherapy trials. The estimate of the combined percent exit was 86.1% (CI 78.6% to 93.6%). These data may be able to serve as a historical control for future monotherapy studies, obviating the need for a placebo/pseudo placebo arm

Evidence-based treatment guidelines and practice parameters have been developed in most areas of medicine. They are important because insurance companies, formulary managers, and health maintenance organizations rely on guidelines for formulary and coverage decisions. The methodology for practice parameter development by the AAN is described as it was applied to evaluating AEDs. Systematic criteria are used to classify the evidence as class I, II, III or IV. There is value in designing clinical trials so they will be considered to provide a high level of evidence. The major variables that will be assessed include presence of randomization, use of a control group, use of masked outcome assessment, and in an active-controlled trial, use of an adequate comparator and adequate enrollment to detect a difference if one exists. Minor variables also must be addressed, including a priori definition of the primary outcome variable, clearly defined Inclusion/exclusion criteria, presence of equivalent treatment groups at baseline, adequate duration of assessment to answer the clinical question, and appropriate management and statistical handling of drop-outs. Understanding of the variables that will be considered for treatment guidelines can improve the methodological strength of studies and lead to recommendations for practice

Some epilepsy patients quickly develop resistance to antiepileptic drugs (AEDs). We report a case of a patient with refractory epilepsy with daily seizures who initially responded to levetiracetam daily therapy, but then returned to baseline seizure frequency. However, when levetiracetam was given once weekly, the patient had significantly fewer seizures on the day of and after administration. These results suggest a useful treatment strategy for patients with refractory epilepsy who have developed resistance to AEDs