Faculty Bibliography

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 Some trials have been performed in patients with refractory epilepsy, who are withdrawn from their previous antiepileptic drugs, and converted to monotherapy on a study drug, using a low-dose comparator, frequently called 'pseudo-placebo.'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

Psychogenic nonepileptic seizures (PNES) remain a poorly understood phenomenon for both patients and their physicians. Recent work has begun to focus on the possible psychological underpinnings of this diagnosis, but few studies have focused on specific emotional pathologies. This study sought to investigate the impact of a specific emotional measure: self-reported fear sensitivity. Three patient groups (patients with PNES, patients with epilepsy, and healthy volunteers) were administered the Modified Fear Survey Schedule, along with other neuropsychological batteries. As expected, the PNES and epilepsy cohorts demonstrated elevated levels of depression, anxiety, and comorbid psychiatric conditions. The PNES group independently exhibited a statistically significant higher level of fear sensitivity compared with both patients with epilepsy and healthy volunteers. This fear-specific trait was independent of other comorbid psychological factors or psychiatric conditions. These results suggest that patients with PNES exhibit disproportionately elevated fear sensitivity on self-report measures when compared with patients with epilepsy. This finding may reflect an elevated internal 'setpoint' for appraising the intensity of emotional settings