Cortical Lesions Predict Risk for Secondary Progressive MS

Erik Greb

October 14, 2021

The number of cortical lesions at baseline may indicate a patient's risk of developing secondary progressive multiple sclerosis (MS), according to new research. Cortical lesions also may be an early marker of future disability accumulation.

In the study, patients who had developed secondary progressive MS after 20 years of follow-up had approximately seven cortical lesions at baseline. This number was significantly higher than the baseline number of cortical lesions in patients with clinically isolated syndrome (CIS), relapsing-remitting MS, or primary progressive MS at 20 years.

"Our study represented a clear indication that the assessment, presence, and high number of cortical lesions at diagnosis is one of the tools at the disposal of the neurologist for the early identification of patients with more serious disease course," said Gian Marco Schiavi, MD, a neurology resident at the University of Verona, Italy, during the presentation of his research.

The study was presented October 14 at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2021.

Accumulation of Disability

Previous research has indicated that cortical lesions play a role in the accumulation of disability in MS and the conversion to secondary progressive MS. Other observations suggest that the number of cortical lesions after 30 years of follow-up explains more than 40% of the difference in disability between patients with secondary progressive MS.

The current investigators sought to understand whether cortical lesions at diagnosis could predict a patient's risk for development of secondary progressive MS and risk for disability accumulation. They included 220 patients with MS and approximately 20 years of follow-up in their study.

At the time of diagnosis, all participants underwent 1.5-T MRI with double inversion recovery. Participants also presented for periodic MRI and clinical evaluations.

The researchers used analysis of variance to compare the baseline number of cortical lesions between patients with CIS, relapsing-remitting MS, secondary progressive MS, and primary progressive MS at 20 years.

They also performed a multivariable regression analysis to predict patients' final scores on the Expanded Disability Status Scale (EDSS). Variables included participants' demographic, clinical, and radiological characteristics.

Lesions and Disease Progression

At baseline (the time of diagnosis), 162 patients had relapsing-remitting MS, 45 had CIS, and 12 had primary progressive MS. In all, 106 patients had no cortical lesions, 47 had three or fewer cortical lesions, and 67 had more than three cortical lesions.

At 20 years, 12 patients still had CIS, 152 had relapsing-remitting MS, and 44 had developed secondary progressive MS.

The mean number of cortical lesions at diagnosis was 6.6 in patients with secondary progressive MS at 20 years, which was significantly higher than the mean 1.3 cortical lesions in the other patients (P < .001).

In addition, post-hoc analysis showed that the median number of cortical lesions was significantly higher in patients with secondary progressive MS (6), compared with those with CIS (0; P < .001), relapsing-remitting MS (0; P < .001), and primary progressive MS (4.5; P = .013). Patients with primary progressive MS had a higher number of cortical lesions than patients with CIS and those with relapsing-remitting MS (P = .001).

The investigators also examined disability at 20 years. At that timepoint, mean EDSS score was 1.5 in patients with no cortical lesions, 3.0 in patients with one to three cortical lesions at baseline, and 6.0 in patients with more than three cortical lesions.

In a regression analysis, the number of cortical lesions and EDSS at diagnosis were the best predictors of long-term disability (P < .001). These factors explained about 57% of the variance in EDSS score after 20 years.

"Important Study"

"This important study supports that the presence of cortical lesions at the time of diagnosis is associated with long-term disability and transition to a secondary progressive disease course," Elias S. Sotirchos, MD, assistant professor of neurology at Johns Hopkins University in Baltimore, Maryland, told Medscape Medical News. The study size and long duration of follow-up are important strengths of the findings, he added.

Still, further research is needed to validate cortical lesions as a biomarker in clinical practice. Aside from technical validation issues relating to the identification of cortical lesions, whether cortical lesion burden can be used to guide therapeutic decision-making in MS is not clear, said Sotirchos.

"Notably, these patients were diagnosed and enrolled in this study 20 years ago, prior to the availability of newer disease-modifying therapies [DMTs] that are more effective at preventing inflammatory disease activity in MS," he said, referring to the participants in the current study.

While recent observational studies have suggested that early initiation of higher-efficacy DMTs may reduce long-term disability and risk for transition to secondary progressive MS, the optimal approach to treatment in patients with a new diagnosis remains unclear, said Sotirchos.

Furthermore, it is unknown whether use of higher-efficacy DMTs may affect the risk of future disability in patients with high cortical lesion burden at baseline, said Sotirchos. "Or is it too late, especially considering the modest effects of DMTs in progressive patients, and that cortical lesion burden was higher in patients that are progressive?"

One additional question to be addressed is how baseline cortical lesion burden adds to other factors that neurologists use in clinical practice to stratify patients' risk of future disability, such as spinal cord involvement, motor or sphincter symptoms at onset, poor recovery from attacks, and white matter lesion burden, said Sotirchos.

The source of funding for this study was not reported. Schiavi and Sotirchos have disclosed no relevant financial relationships.

37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2021: Abstract P105. Presented October 14, 2021.

Follow Erik Greb on Twitter: @MedscapeErik.

For more Medscape Neurology news, join us on Facebook and Twitter.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.