Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.15.094938v1?rss=1 Authors: Boonstra, F., Gajamange, S., Noffs, G., Perera, T., Strik, M., Vogel, A., Butzkueven, H., Evans, A., van der Walt, A., Kolbe, S. Abstract: Background: Cerebellar damage is common in people with multiple sclerosis (pwMS) and is associated with worse progression and relapse recovery. Studies into the importance of the cerebellum in pwMS are hampered by limited understanding of cerebellar damage and its relation to cerebellar function in pwMS. Objective: Examine axonal loss, as a primary driver of progressive neurological decline, in the cerebellum using advanced diffusion MRI and compare axonal loss with cerebellar dysfunction in pwMS. Methods: We recruited 55 pwMS and 14 healthy controls. Clinical assessments included scale for the assessment and rating of ataxia (SARA), and Bain tremor ratings. Subjects underwent FLAIR, T1-weighted and diffusion MRI. Cerebellar grey and white matter and lesion volume were calculated. Cerebellar axonal loss was examined with fibre-specific markers. Fibre density and cross-section (FDC) accounts for microscopic and macroscopic changes in a fibre bundle. Results: Loss of cerebellar FDC was associated with increased SARA (r=-0.42, p<0.01) and tremor severity (rho=-0.35, p=0.01). Cerebellar lesion volume correlated with SARA (r=0.49, p<0.01) and tremor severity (rho=0.41, p=0.01). Conclusion: Fibre-specific measures of cerebellar pathology could provide a functionally relevant marker of cerebellar damage in MS. Future trials using fibre-specific markers are needed to further characterize cerebellar pathology in pwMS and understand its significance in disease progression. Copy rights belong to original authors. Visit the link for more info