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.

Vagus nerve stimulation for the treatment of medically intractable seizures. Results of a 1-year open-extension trial. Vagus Nerve Stimulation Study Group.

BACKGROUND: Chronic vagus nerve stimulation (VNS) continues to be evaluated as an adjunctive treatment for medically intractable seizures. A previous randomized controlled trial of 114 patients demonstrated a significant decrease in seizure frequency during 3 months of VNS at effective stimulation levels. OBJECTIVE: To evaluate the efficacy of 1 year of VNS therapy for the treatment of medically refractory partial seizures and the relationship between initial and long-term response. PATIENTS AND METHODS: All patients exiting the randomized controlled study of VNS for treatment of medically refractory partial seizures were offered indefinite treatment extension as part of an open-label trial. One hundred (88%) of 114 patients completed 12 months of VNS treatment at effective stimulation levels. Fourteen patients discontinued VNS treatment prior to 1 year, principally because of the treatment's lack of efficacy. These 14 patients were retained in the present analysis using an intent-to-treat approach. Antiepileptic drug use was monitored throughout the trial. Seizure frequency was analyzed in 4 sequential 3-month treatment periods. RESULTS: Compared with pretreatment baseline, there was a significant decrease in seizure frequency during each of the 3-month treatment periods. Seizure frequency was reduced by a median of 20% during the first 3 months of VNS treatment and by 32% during stimulation months 10 through 12. Response during the first 3 months of VNS treatment was a statistically significant predictor of response at months 10 through 12. The observed reduction in seizure frequency was not explained by overall changes in antiepileptic drug use. CONCLUSIONS: The results indicate that VNS remains an effective adjunctive therapy for medically refractory partial seizures over a period of at least 1 year. Response during the first 3 months of treatment is predictive of long-term response.

Weight loss in patients taking felbamate.

Felbamate is a new antiepileptic drug (AED) with a good safety profile. Anorexia has been reported in patients taking felbamate, but the incidence and severity of this side effect have not been adequately investigated. We studied 65 patients with intractable seizures who received adjunctive felbamate therapy as part of clinical research trials or in a compassionate-use program. Mean treatment time on felbamate was 23 weeks (+/- SD 16; range, 6-116 weeks). Forty-nine patients (75%) lost weight during the trials. For subjects older than 15 years, there was a mean weight loss of 3.17 kg or 4.11% of body weight (T = 191.5, z = 4.18, p < 0.001). For subjects 15 years or younger there was a mean weight loss 0.20 kg or a loss of 1.77% of body weight (T = 52.5, NS). Twenty-two patients (34%) lost > 4 kg, and seven patients (11%) lost > 8 kg. Adjunctive treatment of adults with severe epilepsy with felbamate may be associated with clinically significant weight loss.

Polysomnographic sleep measures in Parkinson's disease patients with treatment-induced hallucinations.

Prior studies of sleep in Parkinson's disease (PD) have been compromised by inadequate comparison groups, mixed medication regimens, and absence of quantitative data collection. This is the first study to compare polysomnographic sleep measures in PD patients on only dopaminergic medications with and without hallucinations. We performed two consecutive nights of polysomnography in 10 nondepressed, nondemented PD patients, 5 with and 5 without hallucinations. All patients were being treated with carbidopa/levodopa and a dopaminergic agonist only. Hallucinators and nonhallucinators were group-matched for age, PD duration, severity, and medication doses. Both groups had abnormal sleep records. In particular, there was a reduction in K-complexes and spindle formation, and the frequent occurrence of motor activation during rapid eye movement (REM) sleep consistent with REM behavior disorder. The hallucinator group had a significantly lower sleep efficiency (0.25 in hallucinators vs 0.61 in nonhallucinators, p = 0.006), a reduced total REM sleep time (mean total REM sleep time, 3 minutes in hallucinators vs 50 in nonhallucinators; p = 0.005), and a reduced REM percentage (mean, 5% in hallucinators vs 20% in nonhallucinators; p = 0.011). This study demonstrates that advanced PD patients treated with dopaminergic agents have abnormal sleep patterns and that those with dopaminergic-induced hallucinations have significantly greater REM aberrations than nonhallucinating PD patients.