Cortical Lesions Form Predominantly in Early Multiple Sclerosis

Background and ObjectivesCortical lesions are common in multiple sclerosis (MS) and associated with disability, but their characterization in early MS has been limited. Here, we aimed to characterize cortical lesions in newly diagnosed MS with 7 tesla (T) brain MRI. MethodsAdults within 14 months of relapsing-remitting MS diagnosis underwent 7T brain MRI and clinical evaluation at Mount Sinai. Cortical lesions were identified using T1-weighted (w) (median of three acquisitions) and T2*w images (both at 0.5mm3). Non-cortical brain lesions were segmented on 0.7mm3 T1w images. Lesion burden in newly diagnosed MS was compared with a previously analyzed NIH cohort with longer time since diagnosis, imaged using a similar protocol. Results61 individuals were included in the newly diagnosed MS cohort (mean age 34 {+/-} 4 years; 72% female; median time since diagnosis 5 months, interquartile range [IQR] 6). Cortical lesions were identified in 50/61 (81%) individuals, and subpial cortical lesions were identified in 46 (75%). Median cortical lesion number was 5 (IQR 11), median volume 319 l (IQR 1049). Cortical lesions constituted a median of 14% of total brain lesion volume (IQR 43%), and in 21% of individuals, cortical lesions constituted >50% of total brain lesion volume. Cortical lesion number was associated with worse 9-hole peg test ({rho}=0.33, p=0.008) and Symbol Digit Modalities Test performance ({rho}=-0.29, p=0.02). When pooled with the NIH cohort (n=60, median time since diagnosis 12 years, IQR 17), non-cortical lesion volume was [~]3.5 times higher in people with time since diagnosis >36 months (median 4.7 ml, IQR 8.7) vs [&le;]36 months (median 1.2 ml, IQR 2.4, p<0.001). In contrast, cortical lesion volume was only [~]1.3 times higher in people with time since diagnosis >36 months (median 416 l, IQR 1013) vs [&le;]36 months (median 318 l, IQR 925, p=0.04). Non-cortical lesion volume was moderately associated with time since diagnosis ({rho}=0.54, p<0.001) vs {rho}=0.27 (p<0.001) for cortical lesions. DiscussionCortical lesions are prevalent in newly diagnosed MS and constitute a substantial portion of total lesion burden. Cortical lesion volume is similar in early vs established MS, suggesting most cortical lesions form early in disease.