Effectiveness of Cannabidiol (CBD) as Adjunctive Antiseizure Medication in Patients with Severe Drug Resistant Epilepsy of Known Genetic Etiology
Abstract number :
2.24
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2024
Submission ID :
1107
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Antonietta Coppola, Md phD – Federico II University Hospital of Naples
Emanuele Cerulli Irelli, MD – Sapienza University of Rome, Rome
Marica Rubino, MD – Federico II University of Naples, Italy
claudia Cuccurullo, MD – Federico II University of Naples, Italy
Antonella Riva, MD, PhD – University of Genoa
Pasquale Striano, MD, PhD – University of Genova
Laura Licchetta, Md PhD – IRCCS, Istituto delle Scienze Neurologiche di Bologna, Full Member of the European Reference Network for Rare and Complex Epilepsies
Francesca Bisulli, MD, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of European Reference Network EpiCARE, Bologna, Italy
Lorenzo Muccioli, MD – IRCCS, Istituto delle Scienze Neurologiche di Bologna, Full Member of the European Reference Network for Rare and Complex Epilepsies
alberto Verrotti, Md phD – Department of Pediatrics, University of Perugia, Perugia, Italy
Jana Dominguez Carral, MD – Institut de Recerca Sant Joan de Déu, Barcelona
Carmen Fons, MD – Sant Joan de Déu Children’s Hospital
Alia Ramirez camacho, Md PhD – Institut de Recerca Sant Joan de Déu, Barcelona
Alessandro Orsini, MD – Azienda Ospedaliero Universitaria PIsana
Leonilda Bilo, MD PhD – Federico II University, Naples, Italy
Rationale: Highly purified CBD (hp-CBD) has demonstrated significant efficacy and a favourable safety profile as adjunctive ASM in Dravet syndrome, Lennox–Gastaut syndrome and Tuberous sclerosis complex in randomized controlled trials. The literature reports anecdotal cases of other genetic epilepsies (CDKL5, KCNB1)1,2that have been successfully treated with hp-CBD. These observations suggest that hp-CBD might be effective in a broader range of severe epilepsies.We aimed at assessing in real world practice the effectiveness of CBD as adjunctive treatment in refractory monogenic epilepsies to evaluate whether the genetic diagnosis can predict the response outcome
Methods: drug resistant monogenic epilepsies treated with hp-CBD. The following measures were evaluated at 3,6 and 12 months: % change in seizure frequency; % of patients who experienced a 50% or greater reduction in seizure frequency (responder rate); tolerability; Caregiver Global Impression of Change (CGIC); population stratification (responders vs non-responders) with regard to genetic aetiology
Results: we collected 60 cases (pts) bearing a known pathogenic variant including 12 TSC2, 11 SCN1a, 5 MECP2, 3 CHD2, 2 MEF2C, 2 EPM2a, 2 PAFAH1B1, 2 DNM1. The remaining 21 were single pts. For 49 pts we have a 12 months follow up; four (8%) exited the trial due to worsening of seizure (3) and worsening of overall physical condition (1). Nine pts had a 100% seizure reduction (3 SCN1a;3 TSC2;3 MECP2); four had a seizure reduction of >75%; ten >50%; six >25%; 16 did not improve or had a negligible improvement. The responder rate was 46% (23/49). Hp-CBD was well tolerated (2 pts had elevated liver transaminases, 5 somnolence, 1 diarrhea). None stopped hp-CBD because of side effects. At 12 months, among the TSC2 cases (12pts) six (50%) had 50% or more seizure reduction; three (25%) were seizures free; among the SCN1a cases(8pts), four (50%) had 50% or more seizure reduction; three (40%) were seizures free; both MEF2C did not significantly improve and one withdrew; both EPM2a did not significantly improve and one withdrew. Among MECP2 (3pts) two were seizure free and one had a 70% seizure reduction; one PAFAH1B1 had a 94% seizure reduction and one did not significantly improve. The overall retention rate was 89%; (100% for both TSC2 and SCN1a cases). CGIC was reported as very much improved in 10%; much improved in 32%; improved in 27%; unchanged in 22%; slightly worsened and very much worsened in only one patient respectively (SCN1a and EPM2a)
Conclusions: This preliminary study suggest that hp-CBD might be effective in a wide range of monogenic severe epilepsies. The 12 months the retention rate was nearly 90% notwithstanding only 46% had a significant seizure reduction. Larger numbers are needed to explore whether a genetic etiology can predict the outcome.
< !1. Continuous spike-wave of slow sleep in a patient with KCNB1-related epilepsy responsive to highly purified cannabidiol: a case report and comparison with literature. Ferrera G,et al.Neurocase.2024
< !2. Open-label use of highly purified CBD (Epidiolex) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Devinsky et al. Epilepsy Behav. 2018
Funding: none
Clinical Epilepsy