Authors :
Presenting Author: Ji-Hoon Na, MD, PhD – 강남세브란스병원
Hyunjoo Lee, MD, PhD – 강남세브란스병원
Young-Mock Lee, MD, PhD – 강남세브란스병원
Rationale: Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy (DEE) with drug-resistant multiple seizure types, including tonic and drop seizures, and characteristic EEG findings such as slow spike-and-wave (SSW) and generalized paroxysmal fast activity (GPFA). Cannabidiol (CBD) is FDA-approved for seizures associated with LGS, Dravet syndrome, and tuberous sclerosis complex. Although its mechanism is not fully understood, CBD has demonstrated antiseizure, neuroprotective, and antiinflammatory effects with a favorable safety profile in clinical trials. However, data on its long-term efficacy and genetic response variability remain limited. This study prospectively evaluated the safety and effectiveness of CBD in LGS and examined differences in outcomes based on genetic pathogenic variants (PVs).
Methods:
This single-center prospective study enrolled pediatric patients diagnosed with LGS at Gangnam Severance Hospital between April 2022 and April 2025. Diagnosis was confirmed by three pediatric neurologists using clinical and EEG criteria. All patients underwent diagnostic exome sequencing and chromosomal microarray. CBD was initiated and titrated to 15 mg/kg/day. Patients were categorized as either with or without PVs. Seizure frequency (total and drop seizures), EEG changes, and adverse events were evaluated every 3 months up to 24 months. A responder was defined as ≥50% seizure reduction. Comparative analysis between groups was performed at each time point.
Results:
Among 51 screened patients, 31 met criteria (12 with PVs, 19 without). At 6 months, drop seizure reduction was greater in the PV-negative group (P=0.0329). This trend was not significant at later time points. EEG improvement at 3 months was also more frequent in patients without PVs (P< 0.01). Overall, ≥50% responder rates for drop seizures reached 100% at 12 months. Common side effects included diarrhea (48.4%), abdominal symptoms (32.3%), and drowsiness (29.0%), all within 3 months. Two serious adverse events led to treatment discontinuation.