Lateralized seizure termination: relationship to outcome following anterior temporal lobectomy.

Determination of side of seizure onset is critical for a successful outcome following epilepsy surgery. Little is known about the significance of lateralized seizure termination. Sustained seizure activity contralateral to side of seizure onset, following termination of ictal activity ipsilateral to side of onset, may suggest the presence of an independent focus. Such activity, if present, should predict a poor outcome. We studied side of seizure termination in 13 patients undergoing monitoring with bitemporal depth electrodes and correlated this to outcome following anterior temporal lobectomy (ATL). Side of seizure onset was determined for all seizures during that evaluation. Based on side of final cessation of ictal activity, patients were classified as having ipsilateral final termination or simultaneous termination (Group 1; N=6) or contra-lateral or mixed final termination (Group 2; N=7). The Duke outcome classification system was used. At the end of 2 years follow-up, 6/6 patients in Group 1 and 3/7 patients in Group 2 were seizure free. We conclude that lateralized seizure termination during evaluation with depth electrodes may be useful in predicting outcome following ATL. Continued seizure activity contralateral to side of seizure onset (following termination of ictal activity ipsilateral to side of onset) predicts a poor outcome. This may indicate the presence of an independent seizure focus opposite to the side of surgery.

Pharmacokinetics of levetiracetam.

Major considerations in the acceptance and impact of new antiepileptic drugs include their pharmacokinetics and their potential for interaction with other drugs. The pharmacokinetics of levetiracetam, a newly approved add-on antiepileptic agent for partial-onset seizures in adults, has been evaluated in 27 phase I and II studies. Consistent findings in these studies include rapid and complete oral absorption, linear dose kinetics, a minimal degree of protein binding, and predominantly renal excretion. Because of the lack of hepatic metabolism and low protein binding, the risk of interaction with other drugs is considered low.

Does cognitive-behavioral insomnia therapy alter dysfunctional beliefs about sleep?

STUDY OBJECTIVES: This study was conducted to exam the degree to which cognitive-behavioral insomnia therapy (CBT) reduces dysfunctional beliefs about sleep and to determine if such cognitive changes correlate with sleep improvements. DESIGN: The study used a double-blind, placebo-controlled design in which participants were randomized to CBT, progressive muscle relaxation training or a sham behavioral intervention. Each treatment was provided in 6 weekly, 30-60-minute individual therapy sessions. SETTING: The sleep disorders center of a large university medical center. PARTICIPANTS: Seventy-five individuals (ages 40 to 80 years of age) who met strict criteria for persistent primary sleep-maintenance insomnia were enrolled in this trial. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants completed the Dysfunctional Beliefs and Attitudes About Sleep (DBAS) Scale, as well as other assessment procedures before treatment, shortly after treatment, and at a six-month follow-up. Items composing a factor-analytically derived DBAS short form (DBAS-SF) were then used to compare treatment groups across time points. Results showed CBT produced larger changes on the DBAS-SF than did the other treatments, and these changes endured through the follow-up period. Moreover, these cognitive changes were correlated with improvements noted on both objective and subjective measures of insomnia symptoms, particularly within the CBT group. CONCLUSIONS: CBT is effective for reducing dysfunctional beliefs about sleep and such changes are associated with other positive outcomes in insomnia treatment.

Interactions between sleep and epilepsy.

Sleep is one of the best-documented factors influencing the expression of seizures and interictal discharges. Janz studied the relation between seizures and the sleep/wake cycle and divided the epilepsies into three categories: nocturnal, awakening, and diffuse. Since then, the effect of sleep on the ictal and interictal manifestations of epilepsy has been studied extensively. Many seizures are activated by sleep or arousal from sleep. Interictal discharges are also seen more commonly during sleep, with the greatest activation seen during nonrapid eye movement sleep. Sleep not only increases the frequency of epileptiform abnormalities, but also may alter their morphology and distribution. Sleep deprivation also facilitates both epileptiform abnormalities and seizures. Seizures, on the other hand, also impact sleep. Epileptic patients demonstrate multiple sleep abnormalities, including an increased sleep latency, fragmented sleep, increased awakenings and stage shifts, and an increase in stages 1 and 2 of nonrapid eye movement sleep. These disturbances may in turn be modulated by antiepileptic treatment. This review summarizes the interactions between sleep and epilepsy, including the timing of seizures during the sleep/wake cycle, the influence of sleep on various seizure disorders, the effects of sleep deprivation, and the changes in sleep patterns caused by seizures and their treatment.

Slow wave sleep rebound and REM rebound following the first night of treatment with CPAP for sleep apnea: correlation with subjective improvement in sleep quality.

Objective: The purpose of this study was to correlate changes in PSG parameters between the diagnostic polysomnogram (dPSG) and the first night of treatment with continuous positive airway pressure (CPAP) (cpapPSG) to subjective improvement in sleep quality.Background: In patients with obstructive sleep apnea syndrome (OSAS), therapy with CPAP results in reduction of sleep latency, stage 1 sleep, arousal index (Al) and respiratory disturbance index (RDI), and increase in stage 2 sleep, REM sleep and REM density. No data exists on the differences in polysomnographic (PSG) parameters in patients who have subjective improvement in sleep quality and those who do not.Methods: We retrospectively reviewed PSG studies of 44 patients with OSAS who presented to the Sleep Disorders Center at Duke University Medical Center. Patient's qualitative assessment of sleep was noted using a Likert-type scale administered the morning after the dPSG and cpapPSG. PSG indices of patients noting subjective improvement were compared to those with no improvement.Results: Patients noting a subjective improvement in sleep quality showed a decrease in the percentages of stage 1 sleep (P<0.001) and an increase in percentages of stages 3 and 4 sleep (slow wave sleep rebound; P<0.007) and stage REM sleep (REM rebound; P<0.008).

Cognitive behavioral therapy for treatment of chronic primary insomnia: a randomized controlled trial.

CONTEXT: Use of nonpharmacological behavioral therapy has been suggested for treatment of chronic primary insomnia, but well-blinded, placebo-controlled trials demonstrating effective behavioral therapy for sleep-maintenance insomnia are lacking. OBJECTIVE: To test the efficacy of a hybrid cognitive behavioral therapy (CBT) compared with both a first-generation behavioral treatment and a placebo therapy for treating primary sleep-maintenance insomnia. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial conducted at a single academic medical center, with recruitment from January 1995 to July 1997. PATIENTS: Seventy-five adults (n = 35 women; mean age, 55.3 years) with chronic primary sleep-maintenance insomnia (mean duration of symptoms, 13.6 years). INTERVENTIONS: Patients were randomly assigned to receive CBT (sleep education, stimulus control, and time-in-bed restrictions; n = 25), progressive muscle relaxation training (RT; n = 25), or a quasi-desensitization (placebo) treatment (n = 25). Outpatient treatment lasted 6 weeks, with follow-up conducted at 6 months. MAIN OUTCOME MEASURES: Objective (polysomnography) and subjective (sleep log) measures of total sleep time, middle and terminal wake time after sleep onset (WASO), and sleep efficiency; questionnaire measures of global insomnia symptoms, sleep-related self-efficacy, and mood. RESULTS: Cognitive behavioral therapy produced larger improvements across the majority of outcome measures than did RT or placebo treatment. For example, sleep logs showed that CBT-treated patients achieved an average 54% reduction in their WASO whereas RT-treated and placebo-treated patients, respectively, achieved only 16% and 12% reductions in this measure. Recipients of CBT also showed a greater normalization of sleep and subjective symptoms than did the other groups with an average sleep time of more than 6 hours, middle WASO of 26.6 minutes, and sleep efficiency of 85.1%. In contrast, RT-treated patients continued to report a middle WASO of 43.3 minutes and sleep efficiency of 78.8%. CONCLUSIONS: Our results suggest that CBT represents a viable intervention for primary sleep-maintenance insomnia. This treatment leads to clinically significant sleep improvements within 6 weeks and these improvements appear to endure through 6 months of follow-up.

Characteristics of valproic acid resistant juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is often exquisitely responsive to treatment with valproic acid (VPA). However, a subset of patients does not respond to this medication and often has intractable seizures. We wanted to identify differences between these two subsets of JME patients. Charts of all JME patients followed at the Duke Epilepsy Center were reviewed. Clinical parameters, electroencephalogram (EEG) findings and magnetic resonance imaging (MRI) data were reviewed. These features were compared between patients with VPA sensitive and VPA resistant JME. Thirty-three patients with JME were identified: 23 (70%) were VPA sensitive (13 females, 10 males; mean age of onset 15.9 years) and 10 (30%) were VPA resistant (5 females, 5 males; mean age of onset 14.1 years). The VPA resistant group had a higher frequency of EEG asymmetries (40% vs. 10%); atypical seizure characteristics including auras and post-ictal confusion (30% vs. 4%); and intellectual deficiency (20% vs. 0%). Clinical characteristics combined with EEG data may help in predicting which JME patients will respond favorably to VPA. This study also raises the issue whether VPA resistant JME is in fact a localization-related epilepsy.

Inhibitory simple partial (non-convulsive) status epilepticus after intracranial surgery.

OBJECTIVES: To report on five patients who developed, 2 to 4 days after an intracranial neurosurgical procedure, new, persistent, focal neurological deficits which were due to inhibitory simple partial (non-convulsive) status epilepticus, and resolved with anticonvulsant treatment. METHODS: The age range of the five patients was 15-74 years. The operations were: aneurysm clipping (three patients) and resections of an oligodendroglioma and a cavernous haemangioma (one patient each). The new focal deficits were: right hemiparesis and aphasia (two patients), aphasia alone (two patients), and left hemiparesis (one patient). The deficits were not explained by CT (obtained in all patients) or cerebral angiography (performed in two). RESULTS: Electroencephalography showed, in all patients, continuous or intermittent focal seizures arising from cortex regionally relevant to the clinical dysfunction. Subtle positive epileptic phenomena (jerking) occurred intermittently in three patients as a late concommitant. Administration of anticonvulsant drugs resulted in significant improvement within 24 hours in four patients, with parallel resolution of ictal EEG activity. The fifth patient improved more slowly. Two patients relapsed when anticonvulsant concentrations fell, and improved again when they were raised. CONCLUSIONS: It is suggested that inhibitory simple partial (non-convulsive) status epilepticus be considered in the differential diagnosis when a new unexplained neurological deficit develops after an intracranial neurosurgical procedure. An EEG may help to diagnose this condition, leading to definitive treatment.

Improved sexual function in three men taking lamotrigine for epilepsy.

Little information exists about the effects of newer antiepileptic drugs (AEDs) on sexual function in men with epilepsy. We report a series of three male veterans whose sexual disorders improved with lamotrigine. All three had partial seizures. One patient was taking phenobarbital and gabapentin and complained of decreased potency and anorgasmia. After lamotrigine was added for better seizure control and the dosage of gabapentin was tapered, anorgasmia improved. The second patient complained of impotence after a rash while taking phenytoin and carbamazepine. Impotence persisted with phenobarbital, valproate, and gabapentin. Eight months after gabapentin was replaced with lamotrigine, impotence improved. The third patient complained of long-standing impotence. Treatment with five AEDs had no effect on the dysfunction. Lamotrigine was added to the carbamazepine regimen; impotence improved with decrease in carbamazepine and increase in lamotrigine. The favorable effect of lamotrigine on sexual disorders in these three patients suggests this drug should be considered under appropriate circumstances for men who have sexual dysfunction while taking other antiepileptic agents.

Seizure outcome after temporal lobectomy for temporal lobe epilepsy: a Kaplan-Meier survival analysis.

OBJECTIVE: To determine seizure outcome and its predictors in patients with medically refractory temporal lobe epilepsy (TLE) after temporal lobectomy (TL). BACKGROUND: TL is the most common surgical procedure performed in adolescents and adults for the treatment of medically refractory TLE. Seizure outcome has been reported extensively during the first few postoperative years, but little is known beyond that time. METHODS: The authors analyzed seizure outcome in 79 patients who underwent TL for epilepsy at the Duke University Medical Center from 1962 through 1984. Patients with less than 2 years of follow-up and degenerative disorders were excluded. Predictors of seizure outcome were analyzed using Kaplan-Meier survival analyses. RESULTS: The mean follow-up was 14 years (range, 2.1 to 33.6 years). Using Engel's classification, 65% of patients were class I, 15% were class II, 11% were class III, and 9% were class IV. At least one postoperative seizure occurred in 55% of subjects. The majority of recurrences (86%) took place within 2 years of surgery. Later recurrences tended not to lead to medical intractability. Higher monthly preoperative seizure frequency was associated with poor seizure outcome. A seizure-free state at 2 years was found to be a better predictor of long-term outcome than the 6-, 12-, and 18-month landmarks. CONCLUSIONS: TL provides sustained, long-term benefit in patients with medically refractory TLE. Seizure-free status at 2 years from the time of surgery is predictive of long-term remission.

A case of sustained massive gabapentin overdose without serious side effects.

Gabapentin is an antiepileptic agent that is indicated for use as adjunctive therapy for partial seizures. It has a relatively benign side effect profile, but little data exists on massive overdoses with this agent. The authors present a case of a patient who received a massive overdose of this agent but suffered no clinically significant toxicity.

Lamotrigine-induced blepharospasm.

Movement disorders such as tremor and ataxia occur commonly during therapy with antiepileptic drugs (AEDs). Dystonias, however, are rare. Blepharospasm, although reported with neuroleptic agents, has never been reported with AEDs. Our patient developed blepharospasm during therapy with lamotrigine.

Succinylcholine induced hyperkalemia and cardiac arrest death related to an EEG study.

Changes in EEGs during cardiac arrest have been described in detail by many authors; however, mortality because of an EEG has never been reported. The authors report the case of a patient who developed cardiac arrest causally related to administration of succinylcholine for reduction of excessive amounts of myogenic artifact during an EEG. This case indicates the need for caution when doing an EEG study in an intensive care unit setting.

Generalized periodic epileptiform discharges: etiologies, relationship to status epilepticus, and prognosis.

Generalized periodic epileptiform discharges (GPEDs) are generalized, synchronous electrographic discharges. This study investigates etiologies, relationship to status epilepticus (SE), and the prognosis for patients with GPEDs. All EEGs with GPEDs performed at Duke University Medical Center between January 1994 and October 1995 were identified. Clinical histories and EEGs were reviewed. They were divided into groups depending on the etiology of the GPEDs, whether the patients were in SE or not, and whether they were alive or not at discharge. A comparison of histories and GPED characteristics among groups was undertaken using parametric and nonparametric t tests. Twenty-five patients were enrolled: 7 (28%) had toxic-metabolic encephalopathy, 10 (40%) had anoxia and toxic-metabolic encephalopathy, and 8 (32%) had a primary neurologic process. Eight patients (32%) were in SE. In the SE group, GPED amplitude was higher (110 versus 80 microV, P < 0.05), GPED duration was longer (0.5 versus 0.3 seconds, P < 0.05), and inter-GPED amplitude was higher (34 versus 17 microV, P < 0.05). Nine patients (36%) were alive at discharge; they were more likely to be younger (51 versus 68 years, P < 0.05), have a better mental status at the time of their EEG, and have a higher inter-GPED amplitude (33 versus 18 microV, P < 0.05). A variety of conditions, including SE, can cause GPEDs. Intergroup differences in historic and GPED features exist between those patients in SE and those not in SE and those with good and poor prognoses.

Correlation of hippocampal neuronal density and FDG-PET in mesial temporal lobe epilepsy.

PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) reveals regional hypometabolism in 60-80% of patients with mesial temporal lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the epileptogenic zone. The pathophysiology underlying this widespread change is unknown. This study evaluated the relation between hippocampal neuronal loss and hypometabolism in patients with MTLE. METHODS: Forty-three patients with MTLE after anterior temporal lobectomy were included. Pathology demonstrated mesial temporal sclerosis (n = 41) or endfolium sclerosis (n = 2). Interictal FDG-PET scans were graded by visual analysis on a scale ranging from normal (grade 1) to severe (grade 5) hypometabolism. Neuronal counting was performed in the subiculum, hippocampal subfields, and dentate granular cell layer (DG). Neuronal density of patients was compared with that of seven autopsy controls. Data were compared by using Student's t tests and Kruskal-Wallis one-way analysis of variance (ANOVA). RESULTS: Significant neuronal loss in CA1 through CA4 and DG was found in patients compared with controls. Neuronal density in the subiculum, CA1, CA4, and DG did not correlate with severity of hypometabolism. However, patients with abnormal FDG-PET had higher neuronal density in CA2 and CA3 versus patients with normal studies. CONCLUSIONS: This study supports a previous observation that degree of FDG-PET hypometabolism does not parallel severity of hippocampal neuronal loss in MTLE.

Seizure onset from periventricular nodular heterotopias: depth-electrode study.

The association between gray matter heterotopias and seizures is well established; whether seizures originate from these lesions is not known. We evaluated three patients with intractable complex partial seizures and periventricular nodular heterotopias (PNHs) with video-EEG monitoring with multiple depth electrodes, including placement in the PNH, to determine whether seizures originate from the PNH. In two of the three patients, all seizures arose from the PNH as low-voltage beta activity. In the third patient, 80% arose from the hippocampi and 20% from the heterotopia. PNHs may serve as an epileptogenic focus in patients with intractable epilepsy.

Ictal cognitive assessment of partial seizures and pseudoseizures.

BACKGROUND: Previous studies suggest that responsiveness is impaired during complex partial seizures (CPS) and pseudoseizures (PS); however, to our knowledge, there has been no systematic comparison using both response and memory testing. OBJECTIVE: To compare CPS with PS using ictal cognitive assessment (ICA) of responsiveness and memory. PATIENTS AND METHODS: We used a nonautomated method of ICA by bedside observers, consisting of family members and staff, during video electroencephalographic monitoring to test responsiveness and memory during the ictal phase in 245 events. We assessed the adequacy of testing and compared the testing results in 31 patients during CPS and 13 patients during PS. RESULTS: The ictal presentation of a command was successful in 58% of the events. The ictal presentation of at least 2 memory items with testing for recall after orientation was adequate in 57% of events. Impaired responsiveness was shown during both CPS and PS. However, some response was detected during 48% of PS compared with 18% of CPS (P<.01). Memory items were recalled during 63% of PS but during only 4% of CPS (P<.001). The International Classification of Epileptic Seizures remained useful, but in 11 events (8%), distinguishing complex from simple partial seizures was difficult. Recall of various types of stimuli (aural-verbal vs visual-pictorial) during ICA did not correlate with the side or location of the seizure focus, but this may have been confounded by the rarity of any memory recall during CPS. CONCLUSIONS: Ictal cognitive assessment by bedside observers is practical and provides the interaction necessary for properly classifying seizures; ICA, especially memory, may help to distinguish CPS from PS.

Migratory leptomeningeal inflammation with relapsing polychondritis.

We report a case of relapsing polychondritis with focal sensorimotor seizures, aseptic meningitis, and migratory leptomeningeal enhancement on contrast MRI. These abnormalities on imaging studies correlated accurately with laterality of the patient's seizures, facilitating early aggressive management of his neurologic symptoms.

Surgical outcome in patients with epilepsy with occult vascular malformations treated with lesionectomy.

PURPOSE: This retrospective study reports the long-term surgical outcome of patients with medically refractory epilepsy and vascular malformations who were treated with lesionectomy. A detailed analysis of surgical failures had been performed in an attempt to define predictors of surgical success and failure. METHODS: Fifteen patients with medically intractable epilepsy and angiographically occult vascular malformations (AOVMs) were treated surgically with lesionectomy at Duke University Medical Center. Lesionectomy consisted of removal of the AOVM and surrounding hemosiderin-stained brain only, without the use of electrocorticography (ECoG) to guide resection. RESULTS: Eleven (73%) patients are seizure free after lesionectomy. Three showed no significant improvement, and one patient died, presumably after a seizure. Age of onset, duration of seizures, age at resection, and gender did not affect outcome. All patients with neocortical AOVMs in whom EEG findings correlated with the site of the lesion were seizure free after lesional resection. Treatment failures were associated with the presence of multiple intracranial lesions, poorly localized or diffuse EEG findings, discordant positron emission tomography (PET) imaging, or with a lesion in close proximity to the limbic system. CONCLUSIONS: Lesionectomy, with removal of surrounding hemosiderin-stained brain, can be considered the procedure of choice in carefully selected patients with epilepsy with occult vascular malformations.

Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia.

Long-range, directed migration is particularly dramatic in the cerebral cortex, where postmitotic neurons generated deep in the brain migrate to form layers with distinct form and function. In the X-linked dominant human disorder periventricular heterotopia (PH), many neurons fail to migrate and persist as nodules lining the ventricular surface. Females with PH present with epilepsy and other signs, including patent ductus arteriosus and coagulopathy, while hemizygous males die embryonically. We have identified the PH gene as filamin 1 (FLN1), which encodes an actin-cross-linking phosphoprotein that transduces ligand-receptor binding into actin reorganization, and which is required for locomotion of many cell types. FLN1 shows previously unrecognized, high-level expression in the developing cortex, is required for neuronal migration to the cortex, and is essential for embryogenesis.