Faculty Bibliography

We compared historical features, surface EEG findings, results of intracarotid sodium amobarbital memory testing (IAT), and outcome after anterotemporal lobectomy (ATL) in patients with mesiotemporal lobe seizure onset with those with more diffuse temporal lobe seizure onset (intracranial EEG). Forty-eight patients evaluated consecutively between July 1985 and October 1991 with both scalp/sphenoidal and intracranial EEG were shown to have seizures originating in one temporal lobe. No patients had temporal lobe tumor or vascular malformation. Thirty-seven of the 48 patients had seizure onset in the amygdala/hippocampus (amyg/hipp). Eleven of the 48 had either temporal neocortical onset or simultaneous amyg/hipp and neocortical onset. Patients with mesial onset seizures were more likely to have lateralized memory impairment on IAT (p = 0.05). We noted a trend toward a difference in age of first risk for epilepsy between the two groups (p = 0.09) but not for a difference in any specific risk factor. There were no significant differences in surface EEG interictal findings. Unlike in previous studies, comparison of outcome between the two groups showed no difference in seizure-free outcome. Sudden unexpected death (SUD) was more frequent in neocortical seizure patients who were not seizure-free (p < 0.05)

We evaluated employment after temporal lobectomy for refractory epilepsy in 86 patients (3.5 to 8 years of follow-up). Seventy-three patients qualified for the work force before and after surgery. Unemployment rates declined after surgery (18 patients [25%] unemployed before surgery, eight patients [11%] unemployed after surgery), and underemployment also tended to diminish. Improvement in occupational status related strongly to the degree of postoperative seizure relief. Seizure-free patients fared better (no unemployment, little underemployment) than patients with some seizure-free years and some years with seizures after surgery, whose high underemployment level persisted. Patients with seizures in each year after surgery fared worst (despite reduced seizure frequency), with increased unemployment after surgery. Age at surgery also influenced vocational outcome in patients who were unemployed before surgery. Historical, educational, cognitive, and behavioral measures did not correlate with vocational outcome. Employment gains came slowly; unemployed patients took up to 6 years to obtain work after surgery. Of 13 students at the time of surgery, 11 have graduated and nine are now employed. We conclude that seizures play a large role in limiting employment, and that by alleviating seizures, temporal lobectomy improves employability in people with refractory epilepsy. Surgery thereby provides benefit to individuals with epilepsy by increasing financial independence and to society by reducing unemployment

We reviewed the historical features, preoperative diagnostic evaluation, operative procedure, and surgical outcome in 16 patients with refractory frontal lobe epilepsy. Clinical expression of the epilepsy varied widely, particularly with respect to seizure characteristics, although high monthly seizure frequency and absence of a risk factor for epilepsy before age 5 occurred more often than in reported in temporal lobe epilepsy patients. Seizures often caused early bilateral movements, were brief, and lacked oroalimentary automatisms and a prolonged postictal state. Both the interictal and ictal scalp EEGs had relatively poor sensitivity and specificity and often either contained no epileptiform abnormalities or were misleading. MRI usually identified structural lesions when these were present, although it was negative in two patients with tumors. In the absence of an MRI lesion, intracranial EEG usually identified the area to be resected, although it too provided misleading information in one case. Surgical procedures consisted of focal resections with or without anterior corpus callosotomy, or of corpus callosotomy alone. Nearly all patients improved after surgery, with a majority (67%) becoming seizure-free (average follow-up, 46 months). Preoperative seizure frequency correlated with seizure relief after surgery, as did age of seizure onset, whereas presence of tumor did not. We conclude that frontal lobe epilepsy warrants aggressive investigation and that surgical treatment often can be successful

Psychogenic seizures may be difficult to distinguish from epileptic seizures lacking electrographic correlate. The presence of concomitant epilepsy or Munchausen syndrome by proxy may increase diagnostic difficulty. Clinical seizure characteristic, suggestion, prolactin levels, and continued recording after medication withdrawal may be useful in reaching a diagnosis. Dissociative disorders may be very common in psychogenic seizure patients

The high intensity sweetener aspartame has been implicated anecdotally in seizure provocation. This possibility was investigated with a randomized, double-blind, placebo-controlled, cross-over study. After an extensive search, 18 individuals (16 adults and 2 children) who had seizures allegedly related to aspartame consumption were admitted to adult or pediatric epilepsy monitoring units where their EEG was monitored continuously for 5 days. Aspartame (50 mg/kg) or identically enpackaged placebo was administered in divided doses at 0800, 1000, and 1200 h on study days 2 and 4. All meals were uniformly standardized on treatment days. No clinical seizures or other adverse experiences were observed after aspartame ingestion. Mean plasma phenylalanine (Phe) concentrations increased significantly after aspartame ingestion (83.6 microM) as compared with placebo (52.3 microM). Results suggest that aspartame, in acute dosage of approximately 50 mg/kg, is no more likely than placebo to cause seizures in individuals who reported that their seizures were provoked by aspartame consumption

The intracarotid amobarbital test (IAT) examines hemispheric memory and language. We set out to determine whether memory performance on the IAT correlated with seizure relief after anterior temporal lobectomy in 117 patients with refractory epilepsy. The IAT assessed recognition memory performance for nine items with correction for false-positive recognitions. We then compared performance of one hemisphere with that of the other, defining a correctly lateralized memory deficit as worse performance when using the hemisphere containing the operated temporal lobe than when using the other hemisphere. The analysis included concurrent factors that might also affect outcome, such as age at first risk for epilepsy, presence or absence of tumor, and Full Scale IQ. A discriminant function analysis demonstrated that patients with a correctly lateralized memory deficit on the IAT had an increased probability of being seizure-free following surgery after controlling for other predictors. The performance of the nonoperated temporal lobe related to outcome, although less strongly. The magnitude of the difference in performance between the two hemispheres and the performance of the operated hemisphere did not relate to outcome. Patients who became seizure-free had an earlier age at first risk than did those with persistent seizures, and tumor presence weakly correlated with postoperative outcome. IQ did not correlate with outcome. We conclude that the IAT predicts seizure relief after anterior temporal lobectomy independent of other known risk factors we examined

Few drugs have been approved by the Food and Drug Administration specifically for the treatment of pediatric patients with epilepsy in the United States. There are many factors that make tests of drugs in this group different from studies among adults. This report reviews issues that must be considered in designing studies that will help bring to market antiepileptic drugs for children. Information on the wide variety of antiepileptic drugs rapidly being developed can only be obtained through well-controlled, well-designed clinical trials. Despite the obstacles and pitfalls, trials among the pediatric population are necessary to establish the unique efficacy and safety profile of each drug and to determine the target, population most likely to benefit from each drug

Generic substitution of antiepileptic drugs (AEDs) has been controversial, with many alleged instances of biologic and therapeutic inequivalence reported. The recall of a generic phenytoin (PHT) formulation used in the Veterans Administration (VA) medical system allowed us to evaluate the question of biologic equivalence systematically in a relatively large number of patients at the Bronx VA Medical Center. Serum PHT levels were 22-31% lower during the period of generic intake as compared with levels in the same patients receiving Dilantin. Review of the literature showed only one other adequately documented report of potential clinically significant inequivalence between a brand name and generic AED. Despite the apparent infrequency of generic inequivalence, several areas in which procedures for certification of therapeutic equivalence should be improved were identified

OBJECTIVE: To provide a rational strategy for the evaluation and long-term management of epilepsy. DATA SOURCES: Articles written between 1964 and 1993, obtained from a MEDLINE search on epilepsy-related topics as well as from the author's personal files, major reference books on antiepileptic drugs, and references identified from these books. STUDY SELECTION: Articles were selected if they contained well-documented information comparing anti-epileptic drugs, represented controlled clinical trials, or were considered 'key' articles of clinical relevance. DATA SYNTHESIS: Epilepsy is a chronic condition requiring careful long-term management. The treatment is complex, involving classification and diagnosis, selection and monitoring of the appropriate antiepileptic agent, and evaluation of the chosen drug's side effects and drug interactions. Because these side effects increase when drugs are combined, monotherapy is recommended. Long-term management issues and optimal drug selection differ from patient to patient. If seizures are not controlled by medication, the patient may have been misdiagnosed or misclassified. Noncompliance, a major cause of apparent unresponsiveness to treatment, should also be ruled out. Recognizing that current therapy is not ideal for many patients, new pharmacologic and surgical therapies are briefly discussed. CONCLUSIONS: Physicians can pursue a rational strategy for the management of epilepsy if they understand the risks and benefits of various pharmacologic and therapeutic options and if they maintain open lines of communication with the patient