Nonlesional diffusely abnormal appearing white matter in clinically isolated syndrome: Prevalence, association with clinical and MRI features, and risk for conversion to multiple sclerosis

Background and Purpose: While diffusely abnormal white matter (DAWM) is a nonlesional MRI abnormality identified in ∼25% of patients with multiple sclerosis (MS), it has yet to be investigated in patients at an earlier disease stage, namely clinically isolated syndrome (CIS). The goals of this study were to (1) determine the prevalence of DAWM in patients with a CIS suggestive of MS, (2) evaluate the association between DAWM and demographic, clinical, and MRI features, and (3) evaluate the prognostic significance of DAWM on conversion from CIS to MS. Methods: One hundred and forty-two CIS participants were categorized into DAWM and non-DAWM groups at baseline and followed for up to 24 months or until MS diagnosis. The primary outcome was conversion to MS (2005 McDonald criteria) within 6 months. Results: DAWM was present in 27.5% of participants, and was positively associated with brainstem symptom onset, receiving corticosteroids, dissemination in space, and T₂ lesion volume. DAWM was associated with an increased risk of conversion to MS over 6 months after adjustment for age and disability (hazard ratio [HR] = 2.24, p = 0.004). This association remained at a trend-level after adjustment for high-risk imaging features (HR = 1.68, p = 0.10). Conclusions: DAWM is present in a similar proportion of patients with CIS and clinically definite MS, and it is associated with increased risk of conversion to MS over 6 months.