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

Lookup NU author(s): Dr Gerard Hall, Dr Peter TaylorORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group. Methods: 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 (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed (d =.42). Maximum volume loss was observed in the corpus medullare (dmax =.49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax =.47), crus I/II (dmax =.39), VIIIA (dmax =.45), and VIIIB (dmax =.40). Earlier age at seizure onset ((Formula presented.) =.05) and longer epilepsy duration ((Formula presented.) =.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor 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 cerebellar subregional damage into neurobiological models of epilepsy.

Publication metadata

Author(s): Kerestes R, Perry A, Vivash L, O'Brien TJ, Alvim MKM, Arienzo D, Aventurato IK, Ballerini A, Baltazar GF, Bargallo N, Bender B, Brioschi R, Burkle E, Caligiuri ME, Cendes F, de Tisi J, Duncan JS, Engel JP, Foley S, Fortunato F, Gambardella A, Giacomini T, Guerrini R, Hall G, Hamandi K, Ives-Deliperi V, Joao RB, Keller SS, Kleiser B, Labate A, Lenge M, Marotta C, Martin P, Mascalchi M, Meletti S, Owens-Walton C, Parodi CB, Pascual-Diaz S, Powell D, Rao J, Rebsamen M, Reiter J, Riva A, Ruber T, Rummel C, Scheffler F, Severino M, Silva LS, Staba RJ, Stein DJ, Striano P, Taylor PN, Thomopoulos SI, Thompson PM, Tortora D, Vaudano AE, Weber B, Wiest R, Winston GP, Yasuda CL, Zheng H, McDonald CR, Sisodiya SM, Harding IH

Publication type: Article

Publication status: Published

Journal: Epilepsia

Year: 2024

Volume: 65

Issue: 4

Pages: 1072-1091

Print publication date: 01/04/2024

Online publication date: 27/02/2024

Acceptance date: 03/01/2024

Date deposited: 19/03/2024

ISSN (print): 0013-9580

ISSN (electronic): 1528-1167

Publisher: John Wiley and Sons Inc


DOI: 10.1111/epi.17881


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Funder referenceFunder name
Centros de Pesquisa, Inovação e Difusão, Fundação Amazônia Paraense de Amparo à Pesquisa
São Paulo Research Foundation
Swiss National Science Foundation