van der Walt, A. | Search bioRxiv

bioRxiv2020

Evaluation of cerebellar function scores in relation to cerebellar axonal loss in multiple sclerosis

BackgroundCerebellar 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. ObjectiveExamine 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 MethodsWe 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. ResultsLoss 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). ConclusionFibre-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.

neuroscience↗

bioRxiv2019

Immunotherapy prevents long-term disability in relapsing multiple sclerosis over 15 years

ObjectiveWhether immunotherapy improves long-term disability in multiple sclerosis has not been satisfactorily demonstrated. This study examined the effect of immunotherapy on long-term disability outcomes in relapsing-remitting multiple sclerosis.\n\nMethodsWe studied patients from MSBase followed for [≥]1 year, with [≥]3 visits, [≥]1 visit per year and exposed to a multiple sclerosis therapy, and a subset of patients with [≥]15-year follow-up. Marginal structural models were used to compare the hazard of 12-month confirmed increase and decrease in disability, EDSS step 6 and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously re-adjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability and MRI activity.\n\nResults14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval 0.43-0.82, p=0.0016), worsening of disability (0.56, 0.38-0.82, p=0.0026) and progress to EDSS step 6 (0.33, 0.19-0.59, p=0.00019). Among 1085 patients with [≥]15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p=10-9) and worsening of disability (0.81, 0.67-0.99, p=0.043).\n\nConclusionsContinued treatment with multiple sclerosis immunotherapies reduces disability accrual (by 19-44%), the risk of need of a walking aid by 67% and the frequency of relapses (by 40-41%) over 15 years. A proof of long-term effect of immunomodulation on disability outcomes is the key to establishing its disease modifying properties.

neuroscience↗