Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

New-onset psychogenic seizures after surgery for epilepsy.

BACKGROUND: The emergence of psychogenic seizures after surgery for epilepsy is not well recognized. OBJECTIVES: To identify the frequency of psychogenic seizures in an 11-year surgical experience and to characterize the patients with this complication. METHODS: Ninety-six patients underwent surgery for epilepsy between 1985 and 1996. The surgical database was reviewed and all patients who experienced postoperative psychogenic seizures were identified. Patients were characterized by sex, age, psychopathologic conditions, full-scale IQ, duration of epilepsy, surgical procedure, and operative complications. Patients were compared with the surgical group as a whole for these variables. SETTING: A comprehensive epilepsy center. RESULTS: Five patients were identified: 3 men and 2 women. Mean full-scale IQ was 73 (range, 66-82). Mean age was 29.8 years (range, 22-36 years). Three patients were diagnosed as having psychosis, 1 with borderline personality disorder and 1 with generalized anxiety. Operations included 4 anterior temporal lobectomies and 1 occipital lobectomy. Two patients experienced operative complications. Compared with the surgical cohort, patients had a higher frequency of preoperative psychopathologic conditions, lower mean full-scale IQ, and a greater occurrence of operative complications. CONCLUSIONS: (1) Patients can develop new-onset psychogenic seizures after surgery for epilepsy. (2) Low full-scale IQ, serious preoperative psychopathologic conditions, and major surgical complications may be risk factors. (3) Atypical postoperative seizures should be evaluated with video electroencephalographic monitoring before concluding that they are epileptic.

Effects of amiodarone on the circadian pattern of sudden cardiac death (Department of Veterans Affairs Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy).

Some antiarrhythmic drugs have been shown to influence the circadian pattern of sudden cardiac death (SCD). The effect of chronic amiodarone therapy on this pattern is unknown. This study determines the circadian pattern of deaths in the Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) and compares the distribution of SCD between the amiodarone and the placebo arms of the trial. CHF-STAT was a multicenter trial that determined whether amiodarone reduces mortality in patients with heart failure and asymptomatic ventricular arrhythmias. The time of death was retrospectively analyzed in patients who died from pump failure and SCD. In patients who died suddenly, the circadian pattern of deaths was compared between patients receiving amiodarone and those receiving placebo. In CHF-STAT, 274 patients died during follow-up. The time of death was available in 65 of the 74 patients who died from pump failure, and in 96 of the 139 patients who died suddenly. There was a circadian variation of all SCDs compared with other deaths with a distinct peak during the morning (p = 0.04). A similar morning peak of sudden cardiac death was found in both the amiodarone (n = 42) and the placebo (n = 54) groups, and the overall circadian pattern did not differ between them (p = 0.16). In contrast, death from pump failure occurred equally distributed over time. Thus, SCD occurs predominantly during the morning, whereas death from heart failure does not exhibit a morning peak. Amiodarone does not influence the circadian pattern of SCD.

Psychogenic status epilepticus induced by a provocative technique.

We report a patient who developed sustained psychogenic seizures after undergoing a provocative technique (PT) for the diagnosis of psychogenic seizures. Because patients are at risk for severe agitation with PT, these diagnostic maneuvers should be used selectively, and the clinician should be prepared to deal with this complication.

Sleep quality in Lyme disease.

Complaints of chronic fatigue as well as sleep disturbances are prevalent in Lyme disease. We compared polysomnographic measures of sleep in patients with documented Lyme disease with those of a group of age-matched normal control subjects. Eleven patients meeting Centers for Disease Control criteria for late Lyme disease with serologic confirmation by enzyme-linked immunosorbent assay and Western blot without a history of other medical or psychiatric illness and 10 age-matched control subjects were studied. Lyme disease patients and controls underwent 2 nights of polysomnography. Multiple sleep latency testing (MSLT) was performed in the patients. Sleep was staged by standard criteria, and continuity of sleep was assessed for each stage of frequency analysis of consecutive epochs. All patients studied reported sleep-related complaints, including difficulty initiating sleep (27%), frequent nocturnal awakenings (27%), excessive daytime somnolence (73%) and restless legs/nocturnal leg jerking (9%). Greater sleep latency, decreased sleep efficiency and a greater arousal index were noted in Lyme patients. The median length of uninterrupted occurrences of stage 2 and stage 4 non-rapid eye movement (NREM) sleep was less in Lyme patients (6.3 +/- 3.0 epochs in patients vs. 11.4 +/- 4.4 epochs in controls for stage 2, p < 0.01, and 4.3 +/- 4.4 epochs in patients vs. 11.2 +/- 6.3 epochs in controls for stage 4, p < 0.01), indicating greater sleep fragmentation. Mean sleep onset latency during the MSLT was normal (12.7 +/- 5.6 minutes). Three patients demonstrated alpha-wave intrusion into NREM sleep. These sleep abnormalities may contribute to the fatigue and sleep complaints common in this disease.

Cerebellar atrophy in patients with long-term phenytoin exposure and epilepsy.

OBJECTIVE: Cerebellar atrophy has been noted in patients with phenytoin exposure. This finding has been attributed by some investigators to seizures, but by others to phenytoin. Previous studies included patients with mental retardation and convulsive seizures. We undertook a study in a group of nonretarded patients with partial epilepsy to better elucidate the cause of the cerebellar atrophy. DESIGN: Case control study. SETTING: Referral population from an epilepsy center. PATIENTS: Thirty-six patients with partial epilepsy and long-term phenytoin exposure were selected from a consecutive sample of admissions to an epilepsy center. Patients with histories of ethanol abuse, perinatal distress, anoxia, status epilepticus, or neurodegenerative disorders were excluded. Age- and sex-matched controls were selected from a pool of healthy volunteers and patients who had undergone magnetic resonance imaging for complaints of headache and dizziness. INTERVENTIONS: All patients and controls underwent magnetic resonance imaging. MAIN OUTCOME MEASURE: Degree of cerebellar atrophy. RESULTS: The magnetic resonance imaging scans were reviewed in a blind fashion. A rating was assigned to each scan based on the degree of cerebellar atrophy. Cerebellar atrophy was significantly more pronounced in patients than in controls. No correlation was found between cerebellar atrophy and variables reflective of seizure severity or degree of phenytoin exposure. CONCLUSIONS: Cerebellar atrophy may be seen in phenytoin-exposed patients with epilepsy in the absence of generalized tonic-clonic seizures or preexistent brain damage. Whether it is the phenytoin or the seizures that play the primary etiologic role remains unanswered. These factors may be synergistic.