RT Journal Article
SR Electronic
T1 Predicting disability progression and cognitive worsening in multiple sclerosis using patterns of grey matter volumes
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 995
OP 1006
DO 10.1136/jnnp-2020-325610
VO 92
IS 9
A1 Colato, Elisa
A1 Stutters, Jonathan
A1 Tur, Carmen
A1 Narayanan, Sridar
A1 Arnold, Douglas L
A1 Gandini Wheeler-Kingshott, Claudia A M
A1 Barkhof, Frederik
A1 Ciccarelli, Olga
A1 Chard, Declan T
A1 Eshaghi, Arman
YR 2021
UL http://jnnp.bmj.com/content/92/9/995.abstract
AB Objective In multiple sclerosis (MS), MRI measures at the whole brain or regional level are only modestly associated with disability, while network-based measures are emerging as promising prognostic markers. We sought to demonstrate whether data-driven patterns of covarying regional grey matter (GM) volumes predict future disability in secondary progressive MS (SPMS).Methods We used cross-sectional structural MRI, and baseline and longitudinal data of Expanded Disability Status Scale, Nine-Hole Peg Test (9HPT) and Symbol Digit Modalities Test (SDMT), from a clinical trial in 988 people with SPMS. We processed T1-weighted scans to obtain GM probability maps and applied spatial independent component analysis (ICA). We repeated ICA on 400 healthy controls. We used survival models to determine whether baseline patterns of covarying GM volume measures predict cognitive and motor worsening.Results We identified 15 patterns of regionally covarying GM features. Compared with whole brain GM, deep GM and lesion volumes, some ICA components correlated more closely with clinical outcomes. A mainly basal ganglia component had the highest correlations at baseline with the SDMT and was associated with cognitive worsening (HR=1.29, 95% CI 1.09 to 1.52, p<0.005). Two ICA components were associated with 9HPT worsening (HR=1.30, 95% CI 1.06 to 1.60, p<0.01 and HR=1.21, 95% CI 1.01 to 1.45, p<0.05). ICA measures could better predict SDMT and 9HPT worsening (C-index=0.69–0.71) compared with models including only whole and regional MRI measures (C-index=0.65–0.69, p value for all comparison <0.05).Conclusions The disability progression was better predicted by some of the covarying GM regions patterns, than by single regional or whole-brain measures. ICA, which may represent structural brain networks, can be applied to clinical trials and may play a role in stratifying participants who have the most potential to show a treatment effect.Processed data and codes used in this study are available on request from qualified investigators.