Emanuele Cerulli Irelli, Adolfo Mazzeo, Marco Perulli, Georgia Ramantani, Domenica Battaglia, Irene Bagnasco, Erica Cognolato, Pasquale Striano, Susanna Negrin, Alberto Danieli, Paolo Bonanni, Francesca F. OPERTO, Carlo Di Bonaventura, Antonietta Coppola, Alessandro ORSINI
This multicenter retrospective study evaluated the effectiveness and safety of highly purified cannabidiol (CBD) in 22 patients with 15q11.2-q13.1 duplication or deletion syndromes (15q-DDS), including 12 with 15q duplication syndrome (dup15q) and 10 with Angelman syndrome (AS). Median (interquartile range [IQR]) age at CBD initiation was 14.5 (10-22.5) years, with a median (IQR) follow-up of 21 (14-33) months. All dup15q and two AS patients presented with a Lennox-Gastaut phenotype. At last observation, mean seizure reduction was 55.7% (95% confidence interval 38.7-72.7), with 63.6% patients achieving ≥50% reduction, 40.9% achieving ≥75% reduction, and 18.2% achieving seizure freedom. Tonic seizures in dup15q and myoclonic seizures in AS showed the most notable reductions. EEG improvement was observed in 7/16 patients, with marked improvement observed in two dup15q patients. Clinical improvement on the Clinical Global Impression-Improvement scale was reported in 72.7%, alongside nonseizure benefits such as improved sleep, behavior, and attention in a subset of patients. CBD was well tolerated; no patient discontinued CBD due to side effects alone, and retention at last visit was 81.8%. These findings suggest that CBD may provide clinically meaningful benefit in patients with 15q-DDS, including seizure reduction and improvements in sleep, behavior, and attention in selected cases. PLAIN LANGUAGE SUMMARY: Epilepsy secondary to 15q11.2-q13.1 duplication or deletion syndromes (15q-DDS) is often severe, making daily life difficult for patients and their families. In this study, treatment with highly purified cannabidiol (CBD) reduced seizures in many patients with 15q-DDS. CBD was generally well tolerated, and caregivers also reported improvements in sleep, behavior, and attention in a number of cases. Overall, these findings suggest that CBD may be a helpful treatment option for people with 15q-DDS.