Multiple Sclerosis (MS) is one of the most debilitating diseases of the central nervous system that is yet to be cured. In this disease, the myelinating sheath of neurons are progressively degraded which lead to a loss in sensory-motor abilities of patient. Small sample sizes, short duration studies and a slow-rate of disability accrual limit our chances of finding a potential cure for multiple sclerosis. In order to curb and cure MS we must have reliable clinical trials that effectively measure MS progression (Cutteret al., 1999). There are various neuro-protective agents in the race but it is difficult to document the progression of demyelination in patients with primary-progressive and secondary-progressive MS. Inglese et al., (2017) proposed to understand whether cerebellar volumes can be used as a reliable and sensitive measure for Primary Progressive MS (PPMS).

            A longitudinal study was conducted to measure cerebellar volumes of 26 patients (age-matched) with Primary-progressive MS and a control group of 20 individuals. The subjects were selected based on a criterion of age, disease progression and disease duration. Inglese and colleagues accounted for a number of biases by conducting MRI scans for all test subjects on the same day and under similar conditions. Standardized tests for the clinical symptoms were uniformly conducted for all test subjects using 25-foot walk and 9-hole-peg tests and recorded as EDSS (Expanded Disability Status Scale) scores. The increase in EDSS score was the independent variable and the measurements of cerebellar volume was the dependent variable. This study aimed to understand how cerebellar volume could be used as a predictor of primary progressive MS. The MRI scans were performed to measure brain volume, GM (Gray Matter) lesions, and WM (White Matter) lesions for all test subjects during baseline and follow-up (after 1 year).

            Since the data collected was for a small sample size, the authors used non-parametric frequentist statistics to assess differences in MRI metric of test subjects (control and patients) during baseline and at follow-up. The authors also accounted for inter-rater variability and measured Intra-class Correlation Coefficient (ICC) and Coefficient of Variation (CV).

            After one year the cortical cerebellar volumes and the cerebellar volumes of patients with PPMS decreased significantly, which strongly indicated towards progression of MS. The authors also found significant correlation between cerebellar cortical volume decrease and increase in EDSS scores which indicated disease progression in five patients. Authors posit that cerebellum is one of the major sites for demyelination and can be considered a good indicator of progression of MS. The authors also tested for the reproducibility of their results on a cohort of 20 individuals from another medical center and results consistently reported a significant decrease in cerebellar volume and cerebellar cortex volume.

            This study was conducted with due consideration for cognitive biases, and the statistical analyses has been presented in an elegant manner. A small sample size was the only limiting factor which prevented authors from drawing population level inferences on the detection of progression of MS through cortical cerebellar and cerebellar volumes. As new neuroprotective agents are discovered, it will be crucial to identify the best treatment to curb the progression of MS. Cerebellar and cerebellar cortex volume can turn out to be a very efficient measure of MS progression. Similar studies with more test subjects can be conceived to validate and augment the scope of this study.

References

Cutter, G. R., Baier, M. L., Rudick, R. A., Cookfair, D. L., Fischer, J. S., Petkau, J., … Confavreux, C. (1999). Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain, 122(5), 871–882. https://doi.org/https://doi.org/10.1093/brain/122.5.871

Inglese, M., Petracca, M., Mormina, E., Achiron, A., Straus-Farber, R., Miron, S., … Sormani, M. P. (2017). Cerebellar volume as imaging outcome in progressive multiple sclerosis. PLoS ONE, 12(4), 1–11. https://doi.org/10.1371/journal.pone.0176519