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Journal Articles Brain - A Journal of Neurology Year : 2020

Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability

Anne Kerbrat (1, 2, 3, 4, 5) , Charley Gros (1, 2) , Atef Badji (1, 2, 6) , Elise Bannier (3, 7, 8, 9, 4) , Francesca Galassi (7, 8, 9, 4) , Benoît Combès (7, 8, 9, 4) , Raphaël Chouteau (10, 4, 5) , Pierre Labauge (11) , Xavier Ayrignac (11) , Clarisse Carra Dallière (11) , Josefina Maranzano (12, 13, 14) , Tobias Granberg (15, 16) , Russell Ouellette (16, 15) , Leszek Stawiarz (16, 15) , Jan Hillert (16, 15) , Jason Talbott (17, 18, 19, 20) , Yasuhiko Tachibana (21) , Masaaki Hori (22) , Kouhei Kamiya (22) , Lydia Chougar (23) , Jennifer Lefeuvre (24, 25) , Daniel Reich (24, 25) , Govind Nair (24, 25) , Paola Valsasina (26, 27, 28) , Maria Rocca (26, 27) , Massimo Filippi (28, 26, 27) , Renxin Chu (29, 30) , Rohit Bakshi (29, 30) , Virginie Callot (31, 32, 33) , Jean Pelletier (32, 34, 33) , Bertrand Audoin (32, 34, 33) , Adil Maarouf (34, 32, 33) , Nicolas Collongues (35, 36, 37, 38) , Jerome de Sèze (35, 36, 37, 38) , Gilles Edan (10, 5, 4) , Julien Cohen-Adad (1, 2, 39, 40)
1 EPM - École Polytechnique de Montréal
2 IBBME - Institute of Biomaterials and Biomedical Engineering [Ontario, Canada]
3 Hôpital Sud [CHU Rennes]
4 U1128 - Laboratoire de Neurophysiologie et Nouvelles Microscopies
5 CIC - Centre d'Investigation Clinique [Rennes]
6 UdeM - Université de Montréal
7 UR - Université de Rennes
8 Inria Rennes – Bretagne Atlantique
9 IRISA - Institut de Recherche en Informatique et Systèmes Aléatoires
10 Service de Neurologie [CHU Rennes]
11 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
12 Montreal Neurological Institute and Hospital
13 UQTR - Université du Québec à Trois-Rivières
14 MNI - McConnell Brain Imaging Centre
15 Karolinska Institutet [Stockholm]
16 Department of Clinical Neuroscience [Sotckholm]
17 Department of Radiology and Biomedical Imaging [San Francisco]
18 Chan Zuckerberg BioHub [San Francisco, CA]
19 San Francisco General Hospital Medical Center [San Francisco, CA, USA]
20 UC San Francisco - University of California [San Francisco]
21 NIRS - National Institute of Radiological Sciences
22 Toho University Omori Medical Center [Tokyo]
23 CHU Pitié-Salpêtrière [AP-HP]
24 NIH - National Institutes of Health [Bethesda, MD, USA]
25 NINDS - National Institute of Neurological Disorders and Stroke [Bethesda]
26 IRCCS Ospedale San Raffaele [Milan, Italy]
27 Institute of Experimental Neurology - Division of Neuroscience [Milan, Italy]
28 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
29 BWH - Brigham & Women’s Hospital [Boston]
30 HMS - Harvard Medical School [Boston]
31 CEMEREM - Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM]
32 CRMBM - Centre de résonance magnétique biologique et médicale
33 AMU - Aix Marseille Université
34 TIMONE - Hôpital de la Timone [CHU - APHM]
35 BMNST - Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques
36 FMTS - Fédération de Médecine Translationnelle de Strasbourg
37 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
38 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
39 CRIUGM - Centre de recherche de l'Institut universitaire de gériatrie de Montreal
40 UQAM - Université du Québec à Montréal = University of Québec in Montréal
Lydia Chougar

Abstract

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 < 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 < 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P < 0.0001), brainstem (r = 0.45, P < 0.0001) and spinal cord (r = 0.57, P < 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.

Dates and versions

inserm-02910842 , version 1 (09-12-2020)
inserm-02910842 , version 2 (18-01-2021)

Identifiers

Cite

Anne Kerbrat, Charley Gros, Atef Badji, Elise Bannier, Francesca Galassi, et al.. Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability. Brain - A Journal of Neurology , 2020, 143 (7), pp.2089-2105. ⟨10.1093/brain/awaa162⟩. ⟨inserm-02910842v2⟩
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