Here, we assessed damage of cortex, deep grey matter, cerebellum and cervical cord to determine their relative contributions to the main clinical disability (EDSS) milestones in a multicentre cohort of 198 multiple sclerosis (MS) patients. The main determinants of EDSS=3.0 were cervical cord and thalamic atrophy, and brain lesion burden. The EDSS=4.0 milestone was better explained by cortical atrophy, together with cord and cerebellar damage, while the only predictor of EDSS=6.0 was cervical cord damage. This study is shading light on the differential weight of inflammatory and neurodegenerative processes leading to disability accumulation across various MS disease phases.
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