Ictal and Postictal Central Apnea in DEPDC5-Related Epilepsy

Stefano Meletti; Gian Marco Duma; Margherita Burani; Alberto Danieli; Giada Giovannini; Elisa Osanni; Elisa Micalizzi; Fabiana Mambretti; Matteo Pugnaghi; Anna E Vaudano; Paolo Bonanni

doi:10.1212/NXG.0000000000200183

Ictal and Postictal Central Apnea in DEPDC5-Related Epilepsy

Neurol Genet. 2024 Aug 12;10(5):e200183. doi: 10.1212/NXG.0000000000200183. eCollection 2024 Oct.

Affiliation

¹ From the Department of Biomedical Metabolic Sciences and Neurosciences (S.M., M.B., E.M., A.E.V.), University of Modena and Reggio Emilia; Neurophysiology Unit and Epilepsy Centre (S.M., M.B., G.G., M.P., A.E.V.), Neuroscience Department, Modena AOU; Epilepsy Unit (G.M.D., A.D., E.O., P.B.), IRCCS E. Medea Scientific Institute, Conegliano; Neurophysiology Unit and Epilepsy Centre (E.M.), IRCCS Ospedale Policlinico San Martino, Genoa; and Laboratory of Molecular Genetics (F.M.), IRCCS E. Medea Scientific Institute, Bosisio Parini, Lecco, Italy.

Abstract

Objectives: DEPDC5-related epilepsy carries an increased risk of sudden unexpected death in epilepsy. We evaluated the occurrence and features of ictal central apnea (ICA) in patients with pathogenic sequence variant in DEPDC5.

Methods: We reviewed data of 108 patients collected in 2 independent cohorts of patients with focal epilepsy who prospectively underwent long-term video-EEG monitoring (LTVM) with cardiorespiratory polygraphy. All patients underwent (1) at least an overnight polysomnography, (2) a high-field (3T) brain MRI study, and (3) CSF analysis when clinically indicated. Genetic testing (next-generation sequencing [NGS]) was offered for diagnostic purposes to patients with focal epilepsy of unknown etiology.

Results: In this cohort, NGS was finally performed in 29 patients, resulting in DEPDC5 pathogenic mutations in 5 patients. According to the presence of ictal apnea events, 5 of 14 patients with ICA showed pathogenic DEPDC5 variants (35%) while none of the 15 patients without ICA showed pathogenic mutation. Notably, DEPDC5 patients showed ICA in all recorded seizures (n = 15) with apnea duration ranging from 20 seconds to more than 1 minute. All seizures were characterized by motor arrest without overt automatic behaviors during ictal apnea. Scalp EEG showed the involvement of temporal lobe leads in all events. Severe oxygen desaturation was observed in 2 cases.

Discussion: In our cohort, ictal central apnea was a common finding in DEPDC5. These results support (1) the need for respiratory polygraphy during LTVM in DEPDC5-related epilepsy and (2) the potential relevance of genetic testing in patients with focal epilepsy of unknown etiology and ictal apnea.