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MRI Marker Better Predicts Progression Of Multiple Sclerosis

Multiple_Sclerosis demyelination

Atrophied brain lesion volume is the sole marker from MRI scans that can accurately predict which patients with multiple sclerosis will progress to the most severe form of the disease, new research indicates.

Secondary progressive MS, known as SPMS, typically appears 10 to 20 years after the initial onset and causes more physical and cognitive impairments. Of the 1,314 patients in the 5-year study, more than 1,000 were women with an average age of 46.

“This study corroborates initial reports from our group regarding using atrophied lesion volume as a potential MRI marker of disease progression in a large, population-based cohort of MS patients followed in clinical routine,”

says Robert Zivadinov, professor of neurology in the Jacobs School at the University at Buffalo.

Atrophied Brain Lesion Volume

The study builds on previous work that determined that atrophied brain lesion volume was a better indicator of disease progression than the appearance of lesions or whole brain atrophy, both of which researchers have long used as predictors of disease progression.

As part of their routine care, patients with MS undergo MRI scans regularly, so that physicians can monitor new lesions or increased atrophy, which they see as indicators of more disease, or check for any reduction in lesions, generally seen as an indication that medications are working.

atrophied brain lesion MRI
Representative example of an atrophied (“disintegrating”) lesion. Top row shows baseline MRI images, and bottom row shows follow-up MRI images. The magenta region in the bottom right panel shows the part of the original lesion (top) that has disintegrated into cerebrospinal fluid over the intervening period. Nearly 20% of the lesion was lost over time.
Credit: Michael G. Dwyer

Getting Food and Drug Administration approval for a new MS drug requires, among other things, the ability of the new drug to reduce the number of brain lesions a patient has over 24 months.

But the new research demonstrates that atrophied brain lesion volume, which results from disintegration of lesions, and not creation of new lesions or progression of brain atrophy, more accurately signals progression of the disease.

“Neither changes in number and volume of lesions nor the development of whole brain or central brain atrophy showed any predictive power in demonstrating which patients would progress to secondary progressive MS, either from initial presentation of the disease, called clinically isolated syndrome, or the next stage, relapsing remitting MS. The fact that atrophied lesion volume was the only measure that was predictive of conversion to progressive multiple sclerosis, and brain atrophy was not, is a major novel finding of this study.”

Zivadinov says.

Both Pathological Processes

Atrophied brain lesion volume can predict disease progression primarily because it reflects both inflammatory and neurodegenerative pathological processes, which together result in the disappearance of brain lesions into cerebrospinal fluid, Zivadinov says.

In previous work, Zivadinov and colleagues established an MRI marker, which measures brain lesions that cerebrospinal fluid has replaced. Lesions are signs of damage to the brain from physical trauma, a stroke, normal aging, or chronic disease.

It is the disintegration of these lesions into cerebrospinal fluid that the researchers show is the main indicator of disease progression in MS.

“This study showed that atrophied brain lesion volume represents a robust marker for predicting conversion from relapsing-remitting to secondary-progressive stages of MS,”

Zivadinov says.

The routine use of atrophied brain lesion volume as a marker for disease progression in MS depends on the completion of retrospective and prospective studies, some of which this team is already performing, on a large scale in clinical settings.

“Atrophied lesion volume can be measured with a pair of simple MRI scans,” Zivadinov says. “What has not been done yet is to test how visual or qualitative assessment compares to quantitative assessment performed in this study and previous studies we conducted.”

Researchers need a better understanding of the pathophysiological differences between those lesions that disappear compared to those that don’t. Future work will address this.

[1] Antonia Valentina Genovese, Jesper Hagemeier, Niels Bergsland, Dejan Jakimovski, Michael G. Dwyer, Deepa P. Ramasamy, Alexis A. Lizarraga, David Hojnacki, Channa Kolb, Bianca Weinstock-Guttman, and Robert Zivadinov. Atrophied Brain T2 Lesion Volume at MRI Is Associated with Disability Progression and Conversion to Secondary Progressive Multiple Sclerosis. Radiology; Sep 24 2019 https://doi.org/10.1148/radiol.2019190306