SCN1A関連GEFS+におけるフェンフルラミン：有効性、EEG改善、および忍容性に関する多施設共同観察研究

The SCN1A gene is implicated in a broad spectrum of epilepsy phenotypes, ranging from self-limited genetic epilepsy with febrile seizures plus (GEFS+) to severe developmental and epileptic encephalopathies such as Dravet syndrome (DS). While fenfluramine (FFA) has demonstrated strong efficacy in DS, its role in SCN1A-related epilepsies beyond DS has not been thoroughly investigated. We conducted a multicenter observational study including 11 patients with SCN1A-related GEFS+ who received FFA as adjunctive therapy. All patients had previously failed to achieve adequate seizure control with valproate and, in most cases, additional antiseizure medications. FFA was introduced following the DS titration protocol, with a mean dose of 0.39 mg/kg/day. FFA addition led to a mean seizure frequency reduction of 91%, with more than half of the patients achieving complete seizure freedom. Reduced EEG abnormalities were documented in 5/11 patients of the cohort, including complete normalization in 3/11 patients. Furthermore, subjective caregiver reports indicated perceived improvements in patients' alertness and behavioral responses. FFA was well tolerated, with only mild and transient adverse events reported. These findings support the potential role of FFA as an effective and well-tolerated treatment option in patients with SCN1A-related GEFS+. PLAIN LANGUAGE SUMMARY: GEFS+ is a genetic epilepsy frequently caused by changes in the SCN1A gene. In a multicenter real-world study of 11 people with SCN1A-related GEFS+, adding fenfluramine to usual care substantially reduced seizures, with several becoming seizure-free. EEG recordings improved, and caregivers reported better alertness in some patients. Treatment was generally well tolerated, with only mild, temporary side effects.