Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Across all epilepsies, reduced total cerebellar volume was observed ( We provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy.

Déclaration de conflit d'intérêts

L.Vivash. reports research funding from Biogen Australia, Life Molecular Imaging and Eisai. T.J. O’Brien has received consulting fees from Eisai, UCB, Supernus, Biogen, ES Therapeutics, Epidarex, LivaNova, Kinoxis Therapeutics. He participates on the Data Safety Monitoring Board for ES Therapeutics, Kinoxis Therapeutics. He has served as President (past) for Epilepsy Society of Australia, and is the current chair for Australian Epilepsy Clinical Trials Network (AECTN) and the American Epilepsy Society (Translational Research Committee). B. Bender is the cofounder of AIRAmed GmbH, a company that offers brain segmentation. P. Martin. has received honorary as an advisory board member from Biogen unrelated to the submitted work. P. Striano received speaker fees and advisory boards for Biomarin, Zogenyx, GW Pharmaceuticals; research funding by ENECTA BV, GW Pharmaceuticals, Kolfarma srl., Eisai. P.M. Thompson received a research grant from Biogen, Inc., and was a paid consultant for Kairos Venture Capital, Inc., USA, for projects unrelated to this work. C.L. Yasuda has received personal payments from Torrent, Zodiac and UCB. S.M Sisodiya has received research grants from UCB Pharma and Jazz Pharmaceuticals, speakers fees from UCB, Eisai and Zogenix; honoraria or other fees from Eisai, Jazz Pharma, Stoke Therapeutics, UCB and Zogenix. (payments to institution) The remaining authors have no conflicts of interest.