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

ABSTRACT 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, doubleblind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at doses ranging 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\u3c0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P\u3c0.001). Post hoc analysis showed diazepam to be superior to placebo in reducing seizure frequency in both children (P\u3c0.001) and adults (P=0.02), but only in children was it superior with regard to improvement in global outcome (P\u3c0.001). The time to the first recurrence of seizures after initial treatment was longer for the patients receiving diazepam (P\u3c0.001). 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 welltolerated treatment for acute repetitive seizures. (N Engl J Med 1998;338:1869-75.

Efficacy and Safety of VNS Therapy or Continued Medication Management for Treatment of Adults with Drug-Resistant Epilepsy: Systematic Review and Meta-Analysis: Preprint

Preprint for DOI 10.1007/s00415-022-10967-

Risk Factors for Hepatitis C Infection Among Sexually Transmitted Disease-Infected, Inner City Obstetric Patients

Objective: To test the hypothesis that our inner city obstetric patients who have been infected with sexually transmitted diseases (STDs) will have a higher prevalence of hepatitis C virus infection than the general population and to identify specific risk factors and high-risk groups. Methods: All patients in our prenatal clinic (July 1997–April 1999) who tested positive for one or more STDs were asked to return for hepatitis C antibody testing. Medical charts of all patients who returned for hepatitis C testing were reviewed. Results: A total of 106 patients with STDs were tested for hepatitis C. Positive screening tests for anti-hepatitis C antibody were found in 6.6% (7/106) of the patients (95% CI = 2.7–13.1%). This frequency is significantly higher than the hepatitis C prevalence (1.8%) in the general United States population (p = 0.006). Multiple logistic regression analysis confirmed only older age (p = 0.016) and positive HIV status (p = 0.023) to be significant predictors of hepatitis C infection. Conclusions: Inner city STD-infected obstetric patients are at high risk for hepatitis C infection compared with the general population. Increasing age and HIV-positive status are risk factors which are significantly associated with hepatitis C infection

Failure of a Vagus Nerve Stimulator following a Nearby Lightning Strike

We recently reported our experience with implanted vagus nerve stimulators (VNS) in 62 children over a 7-year period. Here, we present a case of a VNS that successfully reduced the number and severity of seizures in a patient with an unusual seizure pattern, and failed to function shortly after a lightning storm. To our knowledge, the failure of VNS or any implantable electrical devices by lightning has not been reported in the literature. This mechanism of electrical interference, while unusual, may require more attention as these devices are expected to be used more frequently.</jats:p

Variability in Serum Concentrations and Clinical Response in Artisanal Versus Pharmaceutical Cannabidiol Treatment of Pediatric Pharmacoresistant Epilepsy

OBJECTIVE: We hypothesized that serum cannabidiol (CBD) concentrations would be higher in patients taking pharmaceutical- versus artisanal-CBD oil, and higher serum CBD concentrations would correlate with increased side effects and decreased seizure frequency. METHODS: This was a retrospective chart review. We included patients with pharmacoresistant epilepsy, treated with artisanal-CBD or pharmaceutical-CBD (Epidiolex), and with quantitative serum CBD concentrations. We tracked epilepsy diagnosis, artisanal-CBD dosage, pharmaceutical-CBD dose, serum CBD concentration, clobazam concentration, N-desmethylclobazam concentration, seizure history (frequency of motor seizures), response to medication (percentage reduction in motor seizures), and side effects. RESULTS: Forty-two patients met inclusion criteria. Mean serum CBD concentration was 51.1 ng/mL (artisanal group) and 124 ng/mL (pharmaceutical group) (p = 0.022). Patients receiving artisanal-CBD had no change in median overall seizures (IQR, -50% to 50%); the pharmaceutical-CBD group had median 50% reduction (IQR, -90% to no change) (p = 0.199). CONCLUSIONS: Pharmaceutical-CBD achieves higher serum CBD concentrations than artisanal-CBD in pediatric patients with refractory epilepsy. These higher CBD concentrations are associated with increased reported adverse effects, but no detectable difference in seizure frequency

Safety and Tolerability of Rufinamide in Children With Epilepsy: A Pooled Analysis of 7 Clinical Studies

Rufinamide is a novel antiepileptic agent recently approved in the United States for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. To help inform clinical decision making, the authors analyzed safety and tolerability data from the entire pediatric population in the rufinamide epilepsy clinical development program. The analysis population comprised 212 rufinamide-treated (age range 3-16 years) and 197 placebo patients (age range 4-17 years) in the double-blind studies, and 391 patients receiving rufinamide in the double-blind and/or open-label extensions. The most common adverse effects observed in rufinamide-treated patients in the double-blind studies were somnolence, vomiting, and headache. Changes in laboratory values, vital signs, and weight were generally clinically insignificant. This pooled analysis of data from pediatric patients in clinical studies of rufinamide for the treatment of seizures, mainly as adjunctive therapy, suggests a favorable safety and tolerability profile in this patient population. </jats:p

Clobazam is equally safe and efficacious for seizures associated with Lennox–Gastaut syndrome across different age groups: Post hoc analyses of short- and long-term clinical trial results

AbstractThe peak age at onset of Lennox–Gastaut syndrome (LGS) is between 3 and 5years. Patients with LGS frequently experience multiple types of treatment-refractory seizures and require lifelong therapy with several antiepileptic drugs. Here, post hoc analyses of clinical trials (phase III trial OV-1012 and open-label extension trial OV-1004) provide short- and long-term efficacy and safety data of adjunctive clobazam in patients with LGS stratified by age at baseline (≥2 to <12years, ≥12 to <17years, and ≥17years). In OV-1012, 301 patients were screened, 238 were randomized, 217 comprised the modified intention-to-treat population, and 177 completed the study. A total of 267/306 patients (61 of 68 from phase II trial OV-1002 and 206 of 238 from phase III trial OV-1012) entered the open-label extension trial. Demographics and clinical characteristics were similar between different age groups in OV-1012 and OV-1004. No differences in efficacy or adverse events were observed across age groups in OV-1012 and OV-1004. The results of these post hoc analyses show that adjunctive clobazam over the short and longterm was similarly effective and well-tolerated in both pediatric and adult patients with LGS