Objective To investigate global and lobular cerebellar volumetries in patients with progressive multiple sclerosis (MS), testing the contribution of cerebellar lobular atrophy to both motor and cognitive performances.
Methods Eighty-two patients with progressive MS and 46 healthy controls (HC) were enrolled in this cross-sectional study. Clinical evaluation included motor and cognitive testing: Expanded Disability Status Scale, cerebellar Functional System score, Timed 25-Foot Walk Test, 9-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test–Revised (BVMT) and California Verbal Learning Test II (CVLT). Cerebellar volumes were automatically obtained using the Spatially Unbiased Infratentorial Toolbox. A hierarchical multiple linear regression analysis was performed to assess the relationship between MRI variables of supratentorial and cerebellar damage (grey matter fraction, T2 lesion volume, metrics of cerebellar atrophy and cerebellar lesion volume) and motor/cognitive scores.
Results Patients with MS exhibited lower cerebellar volumes compared with HC. Regression analysis showed that cerebellar metrics accounted for extra variance in both motor and cognitive performances, with cerebellar lesion volume, cerebellar Lobules VI, Crus I and VIIIa atrophy being independent predictors of 9-HPT, SDMT, BVMT and CVLT performances.
Conclusions Atrophy of specific cerebellar lobules explains different aspects of motor and cognitive disability in patients with progressive MS. Investigation of cerebellar involvement provides further insight into the pathophysiological basis of clinical disability in progressive MS.
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SC and MP contributed equally.
Contributors Study concept and design: MI and FL. Acquisition, analysis or interpretation of data: all authors. Drafting of the manuscript: SC, MP and MI. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: SC and MP. Obtained funding: MI. Study supervision: MI.
Funding This study was supported in part by the National Multiple Sclerosis Society (NMSS RG 5120A3/1), Novartis Pharmaceuticals (CFTY20DUSNC15T) and the Noto Foundation to MI.
Competing interests SC reports personal fees from Sanofi Genzyme. MP reports a research fellowship from FISM. RL reports personal fees from Merck Serono, Biogen, Novartis, Almirall, Genzyme and TEVA. AH reports grants from NMSS and personal fees from TEVA. SK reports personal fees from TEVA. AM reports grants and personal fees from Genzyme/Sanofi-Aventis, Biogen Idec, Novartis, Acorda, Questcor, Accordant Health Services, grants from Genentech and Roche and personal fees from Glaxo Smith Kline, EMD Serono (Merck Serono), ONO, Nuron Biotech and TEVA. AB reports personal fees from Bayer and Bracco. VBM reports personal fees from Novartis, Biogen, Genzyme, TEVA, Almirall, Bayer and Merck. FL reports grants and personal fees from Novartis, Biogen Idec, TEVA Neuroscience, Sanofi/Genzyme, Celgene, grants from Transparency Life Sciences and personal fees from Bayer Healthcare, EMD Serono, Actelion, Acorda, Questcor/Malinckrodt, Roche/Genentech, Medimmune, Osmotica, Xenoport, Receptos, Forward pharma, BBB Technologies, Akros, TG therapeutics, Abbvie, MedDay and Atara Biotherappeutics. MI reports grants from Novartis Pharmaceuticals, National Multiple Sclerosis Society, Noto Foundation, NIH and TEVA Neuroscience.
Provenance and peer review Not commissioned; externally peer reviewed.