Cortical Lesion Burden Associated With Disability Worsening, Transition to Progressive Multiple Sclerosis

Three-year follow-up data presented at the ACTRIMS Forum 2022 suggest cortical lesion burden, particularly subpial lesions, is the primary driver of worsening disability and conversion to secondary progressive MS.

Over 3 years of follow up, cortical lesion (CL) burden, particularly from subpial lesions, was found to be a primary diver of worsening disability and transition to secondary progressive multiple sclerosis (SPMS), according to findings from a recent study. Data were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022, February 24-26, in West Palm Beach, Florida, with investigators positing that results could have implications for patient selection in clinical trials for progressive forms of multiple sclerosis (MS).1

Investigators, led by William Andrew Mullins, BS, postbaccalaureate trainee, Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, NIH, in Bethesda, Maryland, included a total of 59 adults in the study, 42 with relapsing remitting MS (RRMS) and 17 with progressive MS. Participants had a mean age of 49 years (SD, 11) and mean disease duration of 14 years (SD, 11). Included patients underwent 7T brain MRI, using 0.5 mm3 magnetization prepared 2 rapid gradient echo (average of 4 scans) and 0.5 mm3 multi-echo T2* gradient recalled echo. Patients’ CL were segmented by 2 raters.

At baseline and annually, Expanded Disability Status Score (EDSS), 25-Foot Timed Walk (25FTW) test, 9-Hole Peg Test (9HPT), Paced Auditory Serial Addition Test, and Symbol Digit Modality Test scores were measured, with follow up time of 3.0 years (SD, 1.0; range, 1.0-4.2). Also evaluated was the correlation between baseline CL volume, including total and subtypes, white matter lesion volume (WMLV), normalized brain volume (NBV), or spinal cord (SC) lesion number and the change in clinical scores, including absolute change in EDSS and percent change in other tests. Also determined were the difference in baseline MRI measures between those with progression of disability (n = 24) vs those without (n = 35), with disability progression defined as an increase in EDSS of 1 or more for baseline EDSS of less than 6, or an increase in EDSS of 0.5 or greater for baseline EDSS of 6 or greater, or increase in 25FTW or 9HPT by 20% or greater.

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Mullins et al found that baseline CL volume was correlated with a percent increase in T25TW (r = 0.28; P = .048) and the 9HPT (r = 0.43; P = .001). Leukocortical (LC) lesion volume correlated with a percent increase in the 9HPT (r = 0.33; P = .016), and intracortical lesion volume also correlated with percent increase in 9HPT (r = 0.48; P = .0002). Subpial lesion volume correlated with percent increase in 25FTW (r = 0.33; P = .015), as well as 9HPT (r = 0.42; P = .002).

NBV was negatively correlated with percent increase in 25FTW (r = –0.26; P = .042). Comparably, WMLV and SC lesion number did not correlate with changes in patients’ disability. Those with progression of disability (n = 24) had higher baseline total CL volume (median, 1079 µl; IQR, 3184 vs median 304 µl; IQR, 854; P = .010), IC lesion volume (median. 7.6 µl; IQR, 15.6 vs median, 1.9 µl; IQR, 8.5; P =.032), and SP lesion volume (median, 531 µl; IQR, 2039 vs median, 209 µl; IQR, 465; P = .018). No differences were observed in other baseline MRI measures.

“In cross-sectional studies, cortical lesions (CL) are associated with disability and progressive disease,” Mullins et al wrote.“Limited data relate CL to changes in disability over time.”

By last follow up, 5 of 39 patients with RRMS were diagnosed with SPMS. These individuals were found to have a higher baseline CL volume (median, 2200 µl; IQR, 4893 vs median, 338µl; IQR, 804; P =.007), IC lesion volume (median, 15.1 µl; IQR, 22.9 vs median, 2.1µl; IQR 7.9, P =.006), and SP lesion volume (median, 2106 µl; IQR, 5109 vs median, 122 µl; IQR, 338; P =.004). They did not, however, have higher LC lesion volume, WMLV, or SC lesion number.

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1. Mullins WA, Maranzano J, Luciano NJ, et al. Cortical lesion burden is associated with worsening disability over time and conversion to progressive MS. Presented at ACTRIMS Forum 2022; February 24-26; West Palm Beach, FL and Virtual. Sections CE2.3.