Lennox-Gastaut syndrome

LGS is a childhood-onset developmental-and-epileptic encephalopathy defined by the triad of multiple drug-resistant seizure types (including tonic, atonic, and atypical absence), cognitive/behavioral impairment, and a characteristic EEG pattern of diffuse 1.5–2.5 Hz slow spike-and-wave with generalized paroxysmal fast activity. Drop seizures (tonic or atonic) are the most disabling feature. The FDA approved cannabidiol (Epidiolex) for LGS in June 2018 alongside Dravet. Two pivotal trials supported approval: Devinsky et al. GWPCARE3 (NEJM 2018) showed median drop-seizure reductions of 41.9% (20 mg/kg CBD) and 37.2% (10 mg/kg) vs. 17.2% placebo; Thiele et al. GWPCARE4 (Lancet 2018) reported a 43.9% reduction with 20 mg/kg CBD vs. 21.8% with placebo. Common adverse events included somnolence, decreased appetite, diarrhea, and elevated aminotransferases, with clinically relevant clobazam interactions. → See also: Epidiolex, CBD, Dravet syndrome, Epilepsy, Clobazam.