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

Rebecca Kerestes; Andrew Perry; Lucy Vivash; Terence J. O'Brien; Marina K.M. Alvim; Donatello Arienzo; Ítalo K. Aventurato; Alice Ballerini; Gabriel F. Baltazar; Núria Bargalló; Benjamin Bender; Ricardo Brioschi; Eva Bürkle; Maria Eugenia Caligiuri; Fernando Cendes; Jane de Tisi; John S. Duncan; Jerome P. Engel; Sonya Foley; Francesco Fortunato; Antonio Gambardella; Thea Giacomini; Renzo Guerrini; Gerard Hall; Khalid Hamandi; Victoria Ives-Deliperi; Rafael B. João; Simon S. Keller; Benedict Kleiser; Angelo Labate; Matteo Lenge; Cassandra Marotta; Pascal Martin; Mario Mascalchi; Stefano Meletti; Conor Owens-Walton; Costanza B. Parodi; Saül Pascual-Diaz; David Powell; Jun Rao; Michael Rebsamen; Johannes Reiter; Antonella Riva; Theodor Rüber; Christian Rummel; Freda Scheffler; Mariasavina Severino; Lucas S. Silva; Richard J. Staba; Dan J. Stein; Pasquale Striano; Peter N. Taylor; Sophia I. Thomopoulos; Paul M. Thompson; Domenico Tortora; Anna Elisabetta Vaudano; Bernd Weber; Roland Wiest; Gavin P. Winston; Clarissa L. Yasuda; Hong Zheng; Carrie R. McDonald; Sanjay M. Sisodiya; Ian H. Harding

doi:10.1111/epi.17881

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

Rebecca Kerestes^*, Andrew Perry, Lucy Vivash, Terence J. O'Brien, Marina K.M. Alvim, Donatello Arienzo, Ítalo K. Aventurato, Alice Ballerini, Gabriel F. Baltazar, Núria Bargalló, Benjamin Bender, Ricardo Brioschi, Eva Bürkle, Maria Eugenia Caligiuri, Fernando Cendes, Jane de Tisi, John S. Duncan, Jerome P. Engel, Sonya Foley, Francesco FortunatoAntonio Gambardella, Thea Giacomini, Renzo Guerrini, Gerard Hall, Khalid Hamandi, Victoria Ives-Deliperi, Rafael B. João, Simon S. Keller, Benedict Kleiser, Angelo Labate, Matteo Lenge, Cassandra Marotta, Pascal Martin, Mario Mascalchi, Stefano Meletti, Conor Owens-Walton, Costanza B. Parodi, Saül Pascual-Diaz, David Powell, Jun Rao, Michael Rebsamen, Johannes Reiter, Antonella Riva, Theodor Rüber, Christian Rummel, Freda Scheffler, Mariasavina Severino, Lucas S. Silva, Richard J. Staba, Dan J. Stein, Pasquale Striano, Peter N. Taylor, Sophia I. Thomopoulos, Paul M. Thompson, Domenico Tortora, Anna Elisabetta Vaudano, Bernd Weber, Roland Wiest, Gavin P. Winston, Clarissa L. Yasuda, Hong Zheng, Carrie R. McDonald, Sanjay M. Sisodiya, Ian H. Harding

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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 (d_max =.49) and posterior lobe gray matter regions, including bilateral lobules VIIB (d_max =.47), crus I/II (d_max =.39), VIIIA (d_max =.45), and VIIIB (d_max =.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.

Original language	English
Pages (from-to)	1072-1091
Number of pages	20
Journal	Epilepsia
Volume	65
Issue number	4
DOIs	https://doi.org/10.1111/epi.17881
State	Published - Apr 2024
Externally published	Yes

Funding

Funders	Funder number
Eisai
Fundação Amazônia Paraense de Amparo à Pesquisa
Wiley - Monash University
Biogen
UCLH Biomedical Research Centre
Swiss League Against Epilepsy
Monash University
Health and Care Research Wales
Biogen Australia
Tuscany Region for Health
NIHR UCL
Eberhard Karls Universität Tübingen
Australian University Librarians
Centros de Pesquisa, Inovação e Difusão
Epilepsy Society	1184403
FASEP	2022/11786‐4, 06372‐3 11457‐8
Medical Research Council	F1315030, MR/S00355X/1
European Commission	233160
National Institutes of Health	R01 NS1127524, RF1 NS033310, R01 NS106957
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	180365
Italian Ministry of Health fund	NET‐2013‐02355313
UK Research and Innovation	MR/M00841X/1, MR/T04294X/1, P41EB015922, R01MH116147, R01AG058854, G0802012
Fundação de Amparo à Pesquisa do Estado de São Paulo	09230‐5, 04032‐8, 06372‐3, 11457‐8, 2013/03557‐9
National Health and Medical Research Council	APP1176426
Christina Louise George Trust	PNRR‐MUR‐M4C2 PE0000006
Conselho Nacional de Desenvolvimento Científico e Tecnológico	315953/2021‐7

Keywords

anterior lobe
cerebellum
epilepsy
MRI
posterior lobe

Access to Document

10.1111/epi.17881

Cite this

Kerestes, R., Perry, A., Vivash, L., O'Brien, T. J., Alvim, M. K. M., Arienzo, D., Aventurato, Í. K., Ballerini, A., Baltazar, G. F., Bargalló, N., Bender, B., Brioschi, R., Bürkle, E., Caligiuri, M. E., Cendes, F., de Tisi, J., Duncan, J. S., Engel, J. P., Foley, S., ... Harding, I. H. (2024). Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study. Epilepsia, 65(4), 1072-1091. https://doi.org/10.1111/epi.17881

@article{183e5aa7bd3648758f5362c0eb57c70d,

title = "Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study",

abstract = "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.",

keywords = "anterior lobe, cerebellum, epilepsy, MRI, posterior lobe",

author = "Rebecca Kerestes and Andrew Perry and Lucy Vivash and O'Brien, {Terence J.} and Alvim, {Marina K.M.} and Donatello Arienzo and Aventurato, {{\'I}talo K.} and Alice Ballerini and Baltazar, {Gabriel F.} and N{\'u}ria Bargall{\'o} and Benjamin Bender and Ricardo Brioschi and Eva B{\"u}rkle and Caligiuri, {Maria Eugenia} and Fernando Cendes and {de Tisi}, Jane and Duncan, {John S.} and Engel, {Jerome P.} and Sonya Foley and Francesco Fortunato and Antonio Gambardella and Thea Giacomini and Renzo Guerrini and Gerard Hall and Khalid Hamandi and Victoria Ives-Deliperi and Jo{\~a}o, {Rafael B.} and Keller, {Simon S.} and Benedict Kleiser and Angelo Labate and Matteo Lenge and Cassandra Marotta and Pascal Martin and Mario Mascalchi and Stefano Meletti and Conor Owens-Walton and Parodi, {Costanza B.} and Sa{\"u}l Pascual-Diaz and David Powell and Jun Rao and Michael Rebsamen and Johannes Reiter and Antonella Riva and Theodor R{\"u}ber and Christian Rummel and Freda Scheffler and Mariasavina Severino and Silva, {Lucas S.} and Staba, {Richard J.} and Stein, {Dan J.} and Pasquale Striano and Taylor, {Peter N.} and Thomopoulos, {Sophia I.} and Thompson, {Paul M.} and Domenico Tortora and Vaudano, {Anna Elisabetta} and Bernd Weber and Roland Wiest and Winston, {Gavin P.} and Yasuda, {Clarissa L.} and Hong Zheng and McDonald, {Carrie R.} and Sisodiya, {Sanjay M.} and Harding, {Ian H.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.",

year = "2024",

month = apr,

doi = "10.1111/epi.17881",

language = "אנגלית",

volume = "65",

pages = "1072--1091",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "4",

}

Kerestes, R, Perry, A, Vivash, L, O'Brien, TJ, Alvim, MKM, Arienzo, D, Aventurato, ÍK, Ballerini, A, Baltazar, GF, Bargalló, N, Bender, B, Brioschi, R, Bürkle, 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, João, 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, Rüber, 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 2024, 'Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study', Epilepsia, vol. 65, no. 4, pp. 1072-1091. https://doi.org/10.1111/epi.17881

TY - JOUR

T1 - Patterns of subregional cerebellar atrophy across epilepsy syndromes

T2 - An ENIGMA-Epilepsy study

AU - Kerestes, Rebecca

AU - Perry, Andrew

AU - Vivash, Lucy

AU - O'Brien, Terence J.

AU - Alvim, Marina K.M.

AU - Arienzo, Donatello

AU - Aventurato, Ítalo K.

AU - Ballerini, Alice

AU - Baltazar, Gabriel F.

AU - Bargalló, Núria

AU - Bender, Benjamin

AU - Brioschi, Ricardo

AU - Bürkle, Eva

AU - Caligiuri, Maria Eugenia

AU - Cendes, Fernando

AU - de Tisi, Jane

AU - Duncan, John S.

AU - Engel, Jerome P.

AU - Foley, Sonya

AU - Fortunato, Francesco

AU - Gambardella, Antonio

AU - Giacomini, Thea

AU - Guerrini, Renzo

AU - Hall, Gerard

AU - Hamandi, Khalid

AU - Ives-Deliperi, Victoria

AU - João, Rafael B.

AU - Keller, Simon S.

AU - Kleiser, Benedict

AU - Labate, Angelo

AU - Lenge, Matteo

AU - Marotta, Cassandra

AU - Martin, Pascal

AU - Mascalchi, Mario

AU - Meletti, Stefano

AU - Owens-Walton, Conor

AU - Parodi, Costanza B.

AU - Pascual-Diaz, Saül

AU - Powell, David

AU - Rao, Jun

AU - Rebsamen, Michael

AU - Reiter, Johannes

AU - Riva, Antonella

AU - Rüber, Theodor

AU - Rummel, Christian

AU - Scheffler, Freda

AU - Severino, Mariasavina

AU - Silva, Lucas S.

AU - Staba, Richard J.

AU - Stein, Dan J.

AU - Striano, Pasquale

AU - Taylor, Peter N.

AU - Thomopoulos, Sophia I.

AU - Thompson, Paul M.

AU - Tortora, Domenico

AU - Vaudano, Anna Elisabetta

AU - Weber, Bernd

AU - Wiest, Roland

AU - Winston, Gavin P.

AU - Yasuda, Clarissa L.

AU - Zheng, Hong

AU - McDonald, Carrie R.

AU - Sisodiya, Sanjay M.

AU - Harding, Ian H.

PY - 2024/4

Y1 - 2024/4

N2 - 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.

AB - 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.

KW - anterior lobe

KW - cerebellum

KW - epilepsy

KW - MRI

KW - posterior lobe

UR - http://www.scopus.com/inward/record.url?scp=85186573445&partnerID=8YFLogxK

U2 - 10.1111/epi.17881

DO - 10.1111/epi.17881

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 38411286

AN - SCOPUS:85186573445

SN - 0013-9580

VL - 65

SP - 1072

EP - 1091

JO - Epilepsia

JF - Epilepsia

IS - 4

ER -

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

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this