TY - JOUR
T1 - Multiple sclerosis lesions in motor tracts from brain to cervical cord
T2 - Spatial distribution and correlation with disability
AU - Kerbrat, Anne
AU - Gros, Charley
AU - Badji, Atef
AU - Bannier, Elise
AU - Galassi, Francesca
AU - Combès, Benoit
AU - Chouteau, Raphaël
AU - Labauge, Pierre
AU - Ayrignac, Xavier
AU - Carra-Dalliere, Clarisse
AU - Maranzano, Josefina
AU - Granberg, Tobias
AU - Ouellette, Russell
AU - Stawiarz, Leszek
AU - Hillert, Jan
AU - Talbott, Jason
AU - Tachibana, Yasuhiko
AU - Hori, Masaaki
AU - Kamiya, Kouhei
AU - Chougar, Lydia
AU - Lefeuvre, Jennifer
AU - Reich, Daniel S.
AU - Nair, Govind
AU - Valsasina, Paola
AU - Rocca, Maria A.
AU - Filippi, Massimo
AU - Chu, Renxin
AU - Bakshi, Rohit
AU - Callot, Virginie
AU - Pelletier, Jean
AU - Audoin, Bertrand
AU - Maarouf, Adil
AU - Collongues, Nicolas
AU - de Seze, Jérôme
AU - Edan, Gilles
AU - Cohen-Adad, Julien
N1 - Funding Information:
The authors thank Dominique Eden for opening the door to the present study, Benjamin De Leener for the fruitful discussions and Aur?lien Gilliot for his help to correct brain lesion masks. A.K. received scholarships from ARSEP and CHU de Rennes for this research. C.G. received a scholarship from IVADO [EX-2018-4]. A.B. was supported by a Doctoral TransMedTech excellence scholarship. MRI and clinical data acquisition from Rennes, Montpellier and Marseille were supported by the French Hospital Program of Clinical Research (PHRC). This study was partially supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (USA). This MS research was funded by the Swedish Research Council and the Swedish Brain Foundation.
Publisher Copyright:
© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P 5 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P 5 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P 5 0.0001), brainstem (r = 0.45, P 5 0.0001) and spinal cord (r = 0.57, P 5 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.
AB - Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P 5 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P 5 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P 5 0.0001), brainstem (r = 0.45, P 5 0.0001) and spinal cord (r = 0.57, P 5 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.
KW - Corticospinal tract
KW - Disability
KW - MRI
KW - Multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=85088255790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088255790&partnerID=8YFLogxK
U2 - 10.1093/brain/awaa162
DO - 10.1093/brain/awaa162
M3 - Article
C2 - 32572488
AN - SCOPUS:85088255790
VL - 143
SP - 2089
EP - 2105
JO - Brain
JF - Brain
SN - 0006-8950
IS - 7
ER -