‘Usual Suspect’ Lesions Appear Not to Cause Most Severe Disability in Multiple Sclerosis Patients

Stuart SchlossmanMS Research Study and Reports

Presented at 2023 ACTRIMS in San Diego, Ca

 Summary: While brain lesions may be a key marker for Multiple Sclerosis, they may not actually be drivers of disability progression, a new study reports.

Source: University at Buffalo

Brain lesions — areas of brain tissue that show damage from injury or disease — are the biomarker most widely used to determine multiple sclerosis disease progression. But an innovative new study led by the University at Buffalo strongly suggests that the volume of white matter lesions is neither proportional to, nor indicative of, the degree of severe disability in patients.

The results were reported in a poster session on Feb. 24 at the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) in San Diego.

The study compared two sets of 53 MS patients each, ages 30-80, who had the same gender and disease duration but vast and measurable differences in the extent of their physical and cognitive disabilities.

Lesions not a major driver of disability progression

“The absence of material differences in white matter brain lesion burden means this is not a significant driver of severe disability progression, despite the fact that many MS disease-modifying treatments are focused on slowing accumulation of white matter lesions,” said Robert Zivadinov, MD, PhD, principal investigator, professor in the Department of Neurology and director of UB’s Buffalo Neuroimaging Analysis Center and the Center for Biomedical Imaging in UB’s Clinical and Translational Science Institute.

The results are from a first-of-its kind study led by UB that has begun to investigate why a small percentage of people with MS quickly become severely disabled while in others the disease progresses much more slowly.


The individuals in the severely disabled cohort are residents of The Boston Home in Dorchester, Massachusetts, a specialized residential facility for individuals with advanced progressive neurological disorders including MS.

Each of them was then matched with a Buffalo-based “twin” of the same age, sex and disease duration but who experienced far less cognitive and physical disability.

Called Comprehensive Assessment of Severely Affected – Multiple Sclerosis, or CASA-MS, the investigator-initiated, privately funded UB study is focused on identifying biomarkers and cognitive differences among people whose MS disability has become severe compared to others whose disease progresses slowly. More information about how the UB team decided to compare these two populations is available in this news release.

The question of what distinguishes people with severe MS from those who respond well to therapies and continue to live nearly normal lives for decades after diagnosis has confounded patients, caregivers and clinicians for too long, said Zivadinov.

“We couldn’t know what the CASA-MS study would show, because no one has done this research previously,” he said. “What we know now is that the differences between the two groups we studied are striking, and striking in ways that may surprise many of us in this field. I am confident these findings open new doors for both people with severe disabilities, as well as the promise of new insights for the millions more who worry where their disease may take them.”

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