Brain lesions appear not to cause the most severe disability in Multiple Sclerosis (MS) patients, with cortical, deep grey matter and spinal cord damage appearing to be the biggest factors, new research has revealed.
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 in a first-of-its-kind study led by the University at Buffalo, evidence strongly suggests that the volume of white matter lesions is neither proportional to, nor indicative of, the degree of severe disability in patients.
The study compared two sets of 53 MS patients each, aged 30 to 80, who had the same gender and disease duration but vast and measurable differences in the extent of their physical and cognitive disabilities.
“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 Dr Robert Zivadinov, principal investigator and director of UB’s Buffalo Neuroimaging Analysis Center.
The study came after UB researchers 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 were 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.
“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,” said Dr Zivadinov.
“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.”
Despite many available treatments for MS, a subgroup of patients, up to ten per cent of the 2.8 million people with MS worldwide, will develop rapid and progressive, and ultimately severe disability at a relatively young age.
It is widely accepted that MS is characterised by the formation of brain white matter lesions. Yet in this study, participants with severe MS disability showed significantly more gray matter loss in the cortex and thalamus compared to their less-disabled ‘twin’.
Surprisingly, the loss of whole brain volume was comparable among both groups.
While lesion load in both groups was not materially different, the study revealed other important distinctions between the groups in brain scans and cognitive tests.
Severely affected people exhibited lower efficiency in thalamic structural connectivity, meaning they demonstrated lower structural connectivity of the associated brain networks than their less-disabled counterparts.
The study also concluded that members of the severely affected cohort showed more pronounced atrophy of the medulla oblongata — the connection between the brainstem and the spinal cord — which Dr Zivadinov said serves, in this study, as a proxy for spinal cord atrophy.
“These findings suggest that severely disabled MS patients suffer from spinal cord atrophy, an irreversible state of degeneration or loss of spinal cord substance,” he said.
