Donna Bergen

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

Purpose:  We report a multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy.

Placebo‐controlled study of the efficacy and safety of lamotrigine in patients with partial seizures

We evaluated the efficacy and safety of lamotrigine (300 and 500 mg/day) as add-on therapy in a multicenter, randomized, double-blind, parallel-group, placebo-controlled study of 216 patients with refractory partial seizures. During 6 months of treatment, median seizure frequency decreased by 8% with placebo, 20% with 300 mg lamotrigine, and 36% with 500 mg lamotrigine. Seizure frequency decreased by ≥50% in one-third of the 500-mg group and one-fifth of the 300-mg group. Reductions in seizure frequency and seizure days were statistically significant, compared with placebo, for the 500-mg group but not the 300-mg group. Most adverse events were minor and resolved over time. Nine percent of patients on lamotrigine withdrew because of adverse experiences. Lamotrigine plasma concentrations appeared to be a linear function of dose, and the drug did not affect plasma concentrations of concomitant antiepileptic drugs. Lamotrigine was safe, effective, and well tolerated as add-on therapy for refractory partial seizures.

A Comparison of Rectal Diazepam Gel and Placebo for Acute Repetitive Seizures

BACKGROUND Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. METHODS We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at a dosage varying from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses -- one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. RESULTS Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive seizures, 91 (47 children and 44 adults) were treated for an exacerbation of seizures during the study period. Diazepam treatment was superior to placebo with regard to the outcome variables related to efficacy: reduced seizure frequency (P<0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P<0.001). Post hoc analysis showed diazepam to be superior to placebo in reducing seizure frequency in both children (P<0.001) and adults (P=0.02), but only in children was it superior with regard to improvement in global outcome (P<0.001). The time to the first recurrence of seizures after initial treatment was longer for the patients receiving diazepam (P<0.001). Thirty-five patients reported at least one adverse effect of treatment; somnolence was the most frequent. Respiratory depression was not reported. CONCLUSIONS Rectal diazepam gel, administered at home by trained care givers, is an effective and well-tolerated treatment for acute repetitive seizures.

Antiepileptic Drugs, 4th Ed

edited by Rene H. Levy, Richard H. Mattson, and Brian S. Meldrum, 1148 pp., ill., New York, Raven Press, 1995.

Vagus Nerve Stimulation for Treatment of Partial Seizures: 3. Long‐Term Follow‐Up on First 67 Patients Exiting a Controlled Study

179.00 This is the book on the use, toxicity, and pharmacology of antiepileptic drugs, and like the size of the antiepileptic pharmacy, it continues to grow with each edition. The fourth edition was edited by three of the five editors of the last edition. There have been no dramatic departures from the previous organization of the book, but there has been a significant addition of new material. In 1989, the year of the third edition, epileptologists and others …

Efficacy and Tolerability of the New Antiepileptic Drugs, II: Treatment of Refractory Epilepsy. Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society

Summary: Vagus nerve stimulation (VNS) has demonstrated a significant anticonvulsant effect in preclinicalstudies, in pilot studies in humans, and in the acute phaseof a multicenter, double‐blinded, randomized study. After completion of a 14–week, blinded, randomized study, with 31 receiving high (therapeutic) VNS and 36 receiving low (less or noneffective) VNS, 67 patients elected tocontinue in an open extension phase. During the extension phase, all 67 patients received high VNS. Seizurefrequency during the 3‐month treatment blocks was compared with a 12–week baseline. For both groups, all periods of high VNS demonstrated a significant decrease inseizure frequency (p < 0.01 level) as compared with baseline. For the 16–18–month period of VNS, data wereavailable for 26 of the 31 patients randomized to highVNS. This group achieved a 52.0% mean seizure frequency percentage réduction as compared with baseline. For those converted from low to high VNS, data wereavailable for 24 of the 36 patients at the 16–18‐month timeperiod. This group reported a mean seizure frequency percentage reduction of 38.1% as compared with baseline. No significant change in the safetyhde effect profilewas reported during longterm followup. The previouslyreported side effects of hoarsenesslvoice change, coughing, and paresthesia (sensation in neck and jaw) continued to occur during VNS. These side effects were well tolerated. During the follow‐up period, 1 patient died of thrombotic thrombocytopenic purpura (TTP) and 5 patients discontinued treatment because of unsatisfactory efficacy.

Cerebral atrophy, EEG slowing, age, education, and cognitive functioning in suspected dementia

Summary:  Purpose: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies.

Treatment and prognosis of hemiballismus.

Seventy-eight hospital patients, 50 years of age or older, were selected for suspected changes in mentation and for the absence of focal or other organic brain disease. They were studied in relation to education, age, cerebral atrophy (by computerized tomography), electroencephalographic (EEG) slowing, and performance in several neuropsychologic tests. Adequate test-retest reliability of the cognitive measures and interjudge reliability of the cerebral atrophy and EEG measures were demonstrated. Stepwise multiple regression analyses suggested the following: (1) EEG slowing is the strongest and most general pathologic influence on cognition in elderly persons without overt brain disease. (2) Cerebral atrophy independently affects primarily the verbal recall of recent and remote information. (3) Age independently affects primarily recent memory for both verbal and nonverbal material. (4) Formal education is a powerful influence that must be accounted for in all studies of the effects of age on cognition.

Vagus nerve stimulation therapy for epilepsy in older adults

Acute hemiballismus due to a cerebrovascular lesion may have a grave prognosis. In the past nine years, we have treated 11 patients who had an acute onset of hemiballismus believed to be the result of an acute vascular lesion with neuroleptic drugs (most frequently haloperidol). None of the 11 died, and the movement disorders were greatly reduced or eliminated. In eight patients the drugs were withdrawn within six months, without recurrence of the movement disorders. Spinal-fluid homovanillic acid levels were increased in three patients, suggesting that altered dopaminergic feedback mechanisms may be involved in the pathophysiology of hemiballismus. Our observations suggest that the prognosis of hemiballismus is not necessarily as grave as has been believed, and that neuroleptic therapy may alter the outcome of this disorder.

Movement phosphenes in optic neuritis A new clinical sign

Article abstract The authors assessed the efficacy, safety, and tolerability of vagus nerve stimulation (VNS) for refractory epilepsy in 45 adults 50 years of age and older. They determined seizure frequency, adverse effects, and quality of life. At 3 months, 12 patients had a >50% decrease in seizure frequency; at 1 year, 21 of 31 studied individuals had a >50% seizure decrease. Side effects were mild and transient. Quality of life scores improved significantly with time.