Treatment of benzodiazepine-resistant status epilepticus: Systematic review and network meta-analyses.

PURPOSE: Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects. METHODS: All randomized controlled trials studying patients (>1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done. RESULTS: Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin. CONCLUSIONS: Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.

Treatment of children with infantile spasms: A network meta-analysis.

AIM: We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms. METHOD: All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed. RESULTS: Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO4 ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO4 combination, high dose ACTH (with/without vitamin B6 ), high dose prednisolone, and low dose ACTH were 'best'. INTERPRETATION: Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms. WHAT THIS PAPER ADDS: Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag.

Ancient Indian concepts about phenomenology, biology, and therapeutics of epilepsy.

This article discusses etiology, pathogenesis, symptoms, and treatment of epilepsy, as described in Charaka Samhita (translation: Charaka's Compendium) and Sushruta Samhita, the two core texts of Ayurveda, an ancient system of medicine. Ayurveda emphasized amnesia and loss of consciousness as core features of epileptic seizures (Sanskrit: apasmar; translation: apa negation, smaran memory) and recognized that seizures occur due to a disturbance in brain function or flow of "humors" to the brain. Semiology of various seizure types was well described. Epilepsy was attributed to both internal and multiple exogenous factors. Treatment of epilepsy with formulations of naturally occurring substances, their compounding and use, is described in remarkable detail. Lifestyle modifications to protect people with epilepsy are also documented. Cognitive comorbidities of epilepsy were recognized. Although none of the Ayurveda formulations have any empirical evidence supporting their safety or efficacy in the treatment of epilepsy, studies are needed to generate relevant evidence, to recognize their hazards, and to integrate traditional and complementary systems of medicine with modern health care in an informed and safe manner.