Faculty Bibliography

PURPOSE: Women in the United States who have epilepsy give birth to about 20000 newborns every year. Because seizures during late gestation and delivery may seriously affect the fetus, and because primary generalized tonic-clonic (GTC) seizures may occur during labor and delivery in 1-2% of women with epilepsy, we attempted to define the rate, risks, and causes of seizures during labor and delivery. METHODS: To characterize seizures during labor and delivery, we retrospectively analyzed 89 consecutive pregnancies of women with epilepsy on antiepileptic drugs (AEDs). Six epileptologists in our group had treated these patients. We confirmed data and acquired new information by telephone for 83.1% of the pregnancies, and categorized the women as having primary generalized or partial epilepsy. Most of the patients (78%) were on monotherapy during pregnancy; 20% took two AEDs, and 3% took three AEDs during that period. RESULTS: Seizures during labor and delivery occurred in 4/32 (12.5%) patients with primary generalized epilepsy, but in none of the 57 women with partial epilepsy (P<0.05). None of the 38 patients with therapeutic AED levels before labor and delivery had seizures, compared to 3/37 (8.1%) of the subtherapeutic group. However, drug levels were taken at variable times in relation to delivery, limiting their value. Also, the levels sampled were both total and free levels; the latter would be more helpful to determine the adequacy of AED drug coverage. CONCLUSIONS: Maintaining therapeutic AED levels during the last trimester may help prevent seizures during labor and delivery, especially in women with generalized epilepsy. Women with epilepsy who had subtherapeutic AED levels and had been seizure-free may be at-risk for seizures during labor and delivery. Our sample was small, and a random sampling bias may have affected the results

Controlled clinical trials and routine clinical practice demon-strate that levetiracetam is effective as add-on therapy and appears to allow for withdrawal to monotherapy in patients who respond well in the add-on setting. In pivotal clinical trials of adjunctive therapy with levetiracetam 1000 to 3000 mg/day (pooled data), 40% to 54% of patients experienced a 50% or greater reduction in seizure frequency, compared with 18% to 28% of patients treated with placebo. The median percent reduction from baseline in seizure frequency ranged from 36% to 68% for levetiracetam, versus 10% to 23% for placebo. Seizure freedom was achieved by 11% to 35% of those in the levetiracetam treatment group, compared with 3% to 18% of those in the placebo group. (All comparisons statistically significant versus placebo for simple partial, complex partial, and secondarily generalized seizures except for percentage of seizure-free patients with simple partial seizures.) Clinical obser-vations are consistent with these findings

PURPOSE: This report describes our long-term follow-up for combined resective surgery and multiple subpial transections (MSTs) in patients with refractory epilepsy involving eloquent and noneloquent cortex in multiple lobes. Multiple independent seizure foci made these patients poor candidates for conventional surgery. METHODS: MST and resective surgery were used in 13 patients to treat localization-related refractory epilepsy involving eloquent and noneloquent cortex of two or more lobes. Preoperative investigation was followed by invasive monitoring. RESULTS: Eleven patients had MST plus resection involving two different lobes, and two patients had MST plus resection involving three different lobes. MSTs were performed on the primary sensorimotor cortex (eight patients), temporal language area (two patients), Broca's area (one patient), and on both frontal motor and temporal language areas (two patients). Nine patients had a two-stage procedure, and four patients had a three-stage procedure (two consecutive subdural grid studies followed by resections). Average follow-up was 59.2 months (range, 42-98 months). With a modified Engel Outcome Scale, four patients (31%) had a class I outcome; three (23%), class II; three (23%), class III; and three (23%), class IV. Ten (77%) patients had a >50% reduction of seizure burden. CONCLUSIONS: Combined MST and resection can meaningfully improve seizure control in patients with multifocal epilepsy involving eloquent cortex. Prospective randomized studies are needed

This report reviews behavioral adverse events occurring among adults receiving levetiracetam (LEV) or placebo who participated in short-term, placebo-controlled studies in epilepsy (1023), cognitive disorders (719), or anxiety disorders (1510) and epilepsy patients (1393) observed in long-term trials. Behavioral events (affective, psychotic, and suicidal symptoms) were significantly more common among epilepsy patients than cognition or anxiety patients treated with LEV for similar durations (P=0.022). Affective symptoms occurring at 1% or more often in epilepsy placebo-controlled trials included depression (3.8% LEV-2.1% placebo), nervousness (3.8%-1.8%), hostility (2.3%-0.9%), anxiety (1.8%-1.1%), and emotional lability (1.7%-0.2%). Patients with cognitive and anxiety disorders had lower incidences of these symptoms. The incidence of behavioral events in LEV-treated epilepsy patients was lower than rates reported for some other antiepileptic drugs. These data support the hypothesis that some feature related to epilepsy is the cause of many behavioral events rather than the addition of a specific antiepileptic drug

PURPOSE: Subtraction of interictal from ictal single-photon emission computed tomography (SPECT) yields numerous foci that encompass a range of pixel values scattered in the brain. This preliminary study evaluated the significance of this range of values. METHODS: Subtraction images were obtained by registering, normalizing, and subtracting interictal from ictal SPECT for 13 patients. Pixel values of the resulting foci were divided into two groups: group I with 75-100% and group II with 50-75% of the maximal pixel value. Locations of these foci were determined, and concordance with surgical outcomes and scalp and invasive EEG findings was evaluated. RESULTS: In 10 of 13 cases, group I foci showed good concordance with ictal scalp EEG. In addition, group I foci corresponded well to invasive EEG findings in nine of 10 cases. Group I foci had bilateral distributions in seven of 13 cases. In 10 of 13 cases, group I foci corresponded well to regions of surgical resection. Of these 10 patients, nine showed good concordance with scalp EEG, eight showed good invasive EEG concordance, and eight were seizure free after resection. Conversely, group II foci had good concordance with ictal scalp EEG in only five of 13 cases, and invasive EEG findings, in only five of 10 cases. Group II foci had bilateral distributions in 10 of 13 cases. All 10 cases underwent unilateral surgical resections, and all had good surgical outcomes. In six of 13 cases, group II foci showed concordance with surgical sites. Of these six foci, four had poor concordance with scalp EEG, one had poor concordance with invasive EEG, and five had good surgical outcomes. Sensitivity and specificity for seizure localization of Group I foci were 40% and 88% respectively while sensitivity and specificity of Group II foci were 20% and 79% respectively. CONCLUSIONS: Our data demonstrate that foci with 75-100% of maximal pixel values show good concordance with seizure foci, whereas foci of 50-75% may not. Therefore stratifying ictal/interictal differences may improve the specificity and localizing value of subtraction SPECT

PURPOSE: Nonepileptic seizures (NES) are expressions of a psychiatric disease state, usually conversion disorder, that mimic epileptic seizures (ES) but are not associated with the neurophysiologic changes of epilepsy. Conversion has not been demonstrated to emerge from the sleeping state. Emergence out of sleep is usually considered a virtual exclusion criterion for NES, signifying the presence instead of ES. We sought to test this hypothesis. METHODS: We retrospectively reviewed the video-EEG of all patients admitted to our epilepsy unit over a 3-year period, who were suspected of manifesting NES. We examined the relation between NES and the patients' sleep/wake state in this cohort. Two epileptologists blindly reviewed an intermixture of cases suspected to represent NES emerging out of sleep, together with control cases. Classification of each case was made independently. RESULTS: We found that in a small minority of patients (<1%), NES began either while the patient was sleeping, or within several seconds of arousal, well before a plan to simulate a seizure could likely have been formulated in the wakeful state. CONCLUSIONS: In some cases, NES are not the product of the awake mind, but rather represent a psychiatric condition that can be manifest in sleep