Background Cerebellar damage has been implicated in information processing speed (IPS) impairment associated with multiple sclerosis (MS) that might result from functional disconnection in the frontocerebellar loop. Structural alterations in individual posterior lobules, in which cognitive functioning seems preponderant, are still unknown. Our aim was to investigate the impact of grey matter (GM) volume alterations in lobules VI to VIIIb on IPS in persons with clinically isolated syndrome (PwCIS), MS (PwMS) and healthy subjects (HS).
Methods 69 patients (37 PwCIS, 32 PwMS) and 36 HS underwent 3 T MRI including 3-dimensional T1-weighted MRIs. Cerebellum lobules were segmented using SUIT V.3.0 to estimate their normalised GM volume. Neuropsychological testing was performed to assess IPS and main cognitive functions.
Results Normalised GM volumes were significantly different between PwMS and HS for the right (p<0.001) and left lobule VI (p<0.01), left crus I, right VIIb and entire cerebellum (p<0.05 for each comparison) and between PwMS and PwCIS for all lobules in subregions VI and left crus I (p<0.05). IPS, attention and working memory were impaired in PwMS compared with PwCIS. In the whole population of patients (PwMS and PwCIS), GM loss in vermis VI (R2=0.36; p<0.05 when considering age and T2 lesion volume as covariates) were associated with IPS impairment.
Conclusions GM volume decrease in posterior lobules (especially vermis VI) was associated with reduced IPS. Our results suggest a significant impact of posterior lobules pathology in corticocerebellar loop disruption resulting in automation and cognitive optimisation lack in MS.
Trial registration Clinicaltrail NCT01207856, NCT01865357; Pre-results.
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Contributors AM and BB were involved in drafting the manuscript. All authors revised the manuscript for important intellectual content. AM, AR, DL-H, MD and BB were involved in study concept and design. AM, AR, DL-H, FM, MD, PC, NM, DSM, TT, CRGG and BB were involved in analysis and interpretation of the data. AR, MD, DL-H and BB were involved in acquisition of the data. AM and MD were involved in statistical analysis. BB, AR and TT were involved in study supervision and coordination.
Funding AM received a research grant from the Fondation pour la Recherche Médicale (DEA20140630564). This study was supported by ANR-10-LABX-57 Translational Research and Advanced Imaging Laboratory (TRAIL), laboratory of excellence. The SCICOG study was also supported by a grant from Teva, and the REACTIV study by a grant from Merck-Serono. CRGG was supported in part by a grant from the National Multiple Sclerosis Society (grant identifier RG-1501-03141) and by a visiting professorship grant from the Excellence Initiative (IdEx) of the University of Bordeaux.
Competing interests BB, AR and J-CO or their institution received research grants and/or consulting fees from Biogen-Idec, Bayer-Healthcare, Novartis, Genzyme, Roche, Medday, Merck-Serono and Teva. CRGG received a research grant from Sanofi. VP received travel expenses from ARSEP Fondation, Biogen, Teva-Lundbeck and Merk-Serono.
Ethics approval CCP Bordeaux Aquitaine.
Provenance and peer review Not commissioned; externally peer reviewed.