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

Kerestes, Rebecca; Perry, Andrew; Vivash, Lucy; O'Brien, Terence J; Alvim, Marina K M; Arienzo, Donatello; Aventurato, Ítalo K; Ballerini, Alice; Baltazar, Gabriel F; Bargalló, Núria; Bender, Benjamin; Brioschi, Ricardo; Bürkle, Eva; Caligiuri, Maria Eugenia; Cendes, Fernando; de Tisi, Jane; Duncan, John S; Engel, Jerome P; Foley, Sonya; Fortunato, Francesco; ... (23 October 2023). Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study. (bioRxiv). Cold Spring Harbor Laboratory 10.1101/2023.10.21.562994

2023.10.21.562994v1.full.pdf - Published Version
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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 (d=0.42). Maximum volume loss was observed in the corpus medullare (dmax=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (dmax= 0.47), Crus I/II (dmax= 0.39), VIIIA (dmax=0.45) and VIIIB (dmax=0.40). Earlier age at seizure onset (ηρ2max=0.05) and longer epilepsy duration (ηρ2max=0.06) 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.


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.

Item Type:

Working Paper


04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic and Interventional Neuroradiology

UniBE Contributor:

Rebsamen, Michael Andreas, Rummel, Christian, Wiest, Roland Gerhard Rudi


600 Technology > 610 Medicine & health




Cold Spring Harbor Laboratory




Martin Zbinden

Date Deposited:

29 Apr 2024 14:54

Last Modified:

29 Apr 2024 15:04

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

MRI anterior lobe cerebellum epilepsy posterior lobe




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