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Zonisamide is an antiepilepsy drug (AED) with both sodium and calcium channel-blocking properties. This dual mechanism may predict efficacy in some refractory patients, and a broad spectrum of action against different seizure types. Zonisamide has been commercially available in Japan since 1989, and became available in the United States for treatment of adults over the age of 12 with partial-onset seizures in March 2000. Several multicenter clinical trials have been conducted in the United States over the past 15 years. These have included three double-blind, placebo-controlled trials as well as long-term open-label studies. Zonisamide was characterized in these studies as a safe and effective adjunctive treatment for partial-onset seizures. Zonisamide has not yet been studied in the United States as an initial monotherapy, but in one long-term study, some patients were able to discontinue other AEDs and successfully transition to monotherapy. The most frequently reported adverse events were somnolence, dizziness, and anorexia. Current United States labeling states that 12 patients with epilepsy receiving zonisamide had symptomatic kidney stones; however, after more than a dozen years of zonisamide use in Japan, the incidence of kidney stones associated with zonisamide remains low.

This multicentre, randomised, double-blind, placebo-controlled, parallel-group study investigated the efficacy, safety and pharmacokinetics of remacemide hydrochloride in adult patients ( n= 59) with refractory epilepsy, undergoing reduced or discontinued antiepileptic drug (AED) usage, as part of an evaluation for epilepsy surgery. On discontinuation or reduction of maintenance AEDs, patients received remacemide hydrochloride, up to 600 mg daily, or placebo, for up to ten days or until they experienced a fourth complex partial (CPS) or a generalised tonic-clonic (GTC) seizure. Pre- and post-study blood and urine samples were taken for analysis. Remacemide hydrochloride showed a significantly ( P= 0.045) longer median time to fourth seizure compared with placebo (6.8 vs. 3.8 days). Median nine-day seizure counts were significantly ( P= 0.0327) lower with remacemide hydrochloride than placebo (6.2 vs. 12.8). Eleven remacemide hydrochloride patients and six placebo patients completed ten days' treatment. Remacemide and desglycinyl metabolite levels were lower in patients receiving concomitant carbamazepine or phenytoin than in those receiving non-inducing AEDs or remacemide hydrochloride alone. No serious adverse events occurred; all patients receiving remacemide hydrochloride completed the study. Remacemide hydrochloride was well tolerated and showed significant therapeutic activity in this patient population.

Startle-induced seizures are reflex seizures precipitated by a sudden, surprising stimulus, usually auditory. Aetiologies, electroencephalographic correlates, and brain structural abnormalities are variable. Because of the frequent tonic component at onset, falling is a major clinical problem. There is no established drug of choice, and therapy is often unsatisfactory. Adjunctive lamotrigine therapy was used in four consecutive patients with this syndrome seen in a referral epilepsy practice. All four had been refractory to virtually every other drug, but responded dramatically to lamotrigine with elimination of falls from seizures. This observation may serve as pilot data for trials of lamotrigine for startle-induced or other varieties of reflex epilepsies, as adjunctive or monotherapy., (Copyright 1999 BEA Trading Ltd.)

The incidence of psychosis during clinical trials of topiramate was 0.8%, not significantly different from the rate for placebo or reported rates of psychosis in patients with refractory epilepsy. We observed psychotic symptoms in five patients soon after initiation of topiramate therapy. We performed a retrospective chart review of the first 80 patients who began on topiramate after approval for clinical use, between January and April 1997. Symptoms suggestive of psychosis, including hallucinations and delusions, were sought for analysis. Cognitive effects such as psychomotor slowing, confusion, and somnolence were not included. Five patients developed definite psychotic symptoms 2 to 46 days after beginning topiramate. Dosages at symptom onset were 50-400 mg/day. Symptoms included paranoid delusions in four patients and auditory hallucinations in three. Symptoms of psychosis and other psychiatric symptoms resolved quickly with discontinuation of topiramate in three patients, dose reduction from 300 to 200 mg/day in one and with inpatient treatment and neuroleptics in another. One patient had a history of auditory hallucinations, one of aggressive and suicidal thoughts, but three had no significant psychiatric history. Physicians should be aware of the possibility of psychotic symptoms, even in patients without a previous psychiatric history, when prescribing topiramate. Symptoms resolve quickly with discontinuation., (Copyright 1999 BEA Trading Ltd.)

The economic burden of epilepsy is well recognized. However, empirical investigation establishing costs associated with the diagnosis and treatment of non-epileptic psychogenic seizures (NEPS) is lacking. We studied 20 patients with video/EEG monitoring-confirmed NEPS to determine the effect of definitive diagnosis and treatment on medical costs and utilization. A medical resource utilization questionnaire and inpatient medical chart review were employed to calculate utilization information. Medication usage, outpatient visits, emergency room admissions, and diagnostic testing over a 6-month pre-diagnosis and a 6-month post-diagnosis period were compared. There was an 84% average reduction in total seizure-related medical charges in the 6 months following NEPS diagnosis. Average diagnostic testing charges declined 76%, average medication charges decreased 69%, outpatient clinic visits declined 80%, and emergency room visits reduced by 97%. A majority of patients obtaining a definitive inpatient video/EEG-seizure-monitoring-confirmed NEPS diagnosis experience substantial reductions in health care utilization and dollar costs.

Ictal wave form characteristics--frequency, spatial distribution, and duration--were analyzed for 140 complex partial seizures recorded from epidural strip electrodes implanted in 28 patients. None had abnormalities on imaging studies. All had bilateral electrode placements, unilateral seizure onsets, temporal lobectomies, and were followed for a mean of 33 months postoperatively. Sixteen patients (57%) became free of complex partial seizures: 12 had reductions in seizure frequency of at least 50% but were not seizure-free. The only predictor of the seizure-free state was the presence of low voltage fast activity (LVF), in the alpha or beta ranges, localized to one gyrus. This phenomenon occurred in 14/16 seizure-free patients, 2/12 of others (P < 0.001). As seizures progressed, LVF typically increased in amplitude, propagated, and slowed into the theta range. Wave forms were classified into 8 categories based upon their frequency and morphology. Stepwise discriminant analysis of these wave forms, with consideration of whether they were localized or regional, revealed that both frequency and localization were critical for the post-surgical prognosis. The mere presence of a localized seizure onset was unreliable unless the wave form was taken into account. Well-localized rhythmic activity over 8 Hz at seizure onset from epidural subtemporal electrodes predicts surgical success. Slower rhythms imply greater separation in space and time from seizure onset.

VEPs to checkerboard pattern-reversal were recorded from 18 epileptic patients who had EEG photoparoxysmal responses to stroboscopic light. Patients were grouped according to whether seizures were precipitated by environmental light stimuli, or television viewing. Longitudinal studies were conducted on 8 patients treated with valproic acid. We concluded the following: (1) Latency of the major positive peak (P2) of the pattern-reversal VEP was shorter among photosensitive patients than among normal controls. This was especially true of television-sensitive patients. (2) Valproic acid, when effective in controlling seizures, lengthened the P2 latency and decreased VEP amplitude. Studies of drug effects on VEPs may help to elucidate neurochemical mechanisms of the visual cortex. (3) Because of overlap of values with normals, VEP measurements are not at present very sensitive in the diagnosis of photosensitivity. However, longitudinal studies in individuals parallel clinical changes and may be useful as objective measures of improvement.