Measuring Growth of Lesions in MS Better Predicts Disability Progression

Measuring how lesions get bigger over time in multiple sclerosis (MS) can predict long-term disability progression more accurately than other lesion-based assessments, a new study reports.

“Enlargement of T2 [total] lesions, and specifically of its volume, … is more strongly associated with long-term disability progression compared to other conventional T2 lesion-based outcomes,” the researchers wrote.

Notably, the findings suggest that simply counting the number of new or enlarging lesions — as is often done in MS clinical trials — is not as effective a predictor of long-term disability outcomes.

“This finding may help to illuminate an existing gap in the MS literature, given that evidence for correlation between lesion counts and clinical outcomes over mid- to long-term is mixed,” the researchers wrote.

“Lesion expansion is more predictive of long-term disability than the appearance of new lesions,” they added.

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A tool to predict disease progression

The study, “Assessment of T2 lesion-based disease activity volume outcomes in predicting disease progression in multiple sclerosis over 10 years,” was published in Multiple Sclerosis and Related Disorders.

MS is caused by inflammation in the central nervous system, comprised of the brain and spinal cord. Such inflammation leads to areas of damage that are visible on MRI scans as lesions.

The symptoms of MS arise due to the neurological damage in these lesions — but paradoxically, it can be difficult to predict long-term outcomes based on patterns of lesions on MRI scans.

This difficulty is largely attributable to the fact that there’s so much variety among MS lesions over time. New lesions can appear, old ones can resolve, and existing ones may change in shape and size at wildly varying rates, studies have shown.

Given that, analyzing total lesion volume at any one point in time can give relatively little insight into the dynamic processes driving the disease.

Now, an international team of researchers explored an alternative approach: rather than looking at total lesion volume, they analyzed only new or enlarging T2 lesion volume (T2-LV), referring to the lesions visible on MRI scans that represented worsening disease activity.

The team used data from 176 people with relapsing-remitting MS who had participated in a prior clinical trial that followed patients for up to 10 years. About three-quarters of these patients were female. At the study’s start, the patients’ mean age was 30.7, and they had an average disease duration of 4.9 years.

Over the 10-year follow-up, 76 patients had stable disease, while the other 100 experienced confirmed disability progression (CDP). Patients who progressed were significantly older, with a longer disease duration, and a greater rate of relapses.

The researchers conducted a battery of statistical tests looking for associations between new or enlarging T2-LV and other MRI-based parameters, and the risk of CDP after 10 years. Results showed that patients with CDP generally had higher enlarging T2-LV values than those with stable disease; the difference was statistically different from the stable MS group at four and six years of follow-up.

Among all the lesion-based values analyzed, cumulative enlarging T2-LV was the only measure that, starting at three years of follow-up, could predict CDP at 10 years. This measure also was predictive of 10-year CDP at later timepoints.

“Enlarging T2-LV more accurately predicted 10-year disability progression compared to enlarging T2 lesion count, new T2 lesion count or volume, or total T2-LV. This suggests that simply counting new/enlarging lesions or calculating total T2-LV changes may have disadvantages compared to assessing their volume separately,” the researchers concluded.

“More robust predictive ability of enlarging T2-LV toward disability progression in the current study suggests that this measure could be added to future clinical trials in order to enhance the sensitivity of MRI disease activity analyses over long-term follow-up,” they added.