We characterized the frequency of diffusely abnormal white matter (DAWM) in a broad cohort of multiple sclerosis (MS) participants. 35% of clinically isolated syndrome (CIS) and ~60% of MS participants had DAWM. CIS with DAWM had smaller cortical thickness, higher lesion load and higher concentration of neurofilament light chain compared to CIS without DAWM. DAWM may be useful in identifying brains at risk of injury but only in the CIS population when lesion load is low. Longitudinal studies are warranted.
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