Kate Johnson

May 18, 2011

May 18, 2011 (Montreal, Quebec) — Brain and spinal cord atrophy in patients with multiple sclerosis (MS) correlates with the phenotype of the disease and the degree of disability, according to 2 magnetic resonance imaging (MRI) studies presented here at the International Society for Magnetic Resonance in Medicine 19th Annual Meeting and Exhibition.

Both imaging studies point to the future value of MRI in monitoring disease progression and treatment response, suggest the authors.

In the first long-term follow-up of MS patients, conducted over a 10-year period, researchers showed an average loss in brain volume of 5% in 47 patients, compared with a 3% loss in 11 control subjects, reported Antonio Giorgio, MD, from the Department of Neurological and Behavioral Sciences at the University of Siena, Italy.

The mean age of the patients was 37 years; the mean age of the control subjects was 42 years. Mean disease duration was 4.7 years. The majority of patients (n = 40) had the relapsing-remitting phenotype of the disease, 5 had the secondary-progressive phenotype, and 2 had the primary-progressive phenotype.

Conventional MRI performed at baseline and again after 10 years measured global brain volume, normalized white matter (nWM) volume, normalized grey matter (nGM) volume, and ventricular cerebrospinal fluid (vCSF). The researchers assessed the association between phenotype and disability, which was measured on the Expanded Disability Status Scale (EDSS).

At baseline, MS patients had an EDSS score of 2.5, which increased to 3.4 at follow-up (P < .001). The mean number of relapses over 10 years was 3.8, with 3 relapsing-remitting subjects converting to secondary progressive during that period.

Change in nGM volume was significantly higher in MS patients than in control subjects. There were no statistical differences between groups in nWM volume or vCSF, reported Dr. Giorgio.

MS patients were categorized by relapse rate: high, defined as 5 or more relapses in the 10 years; or low, defined as fewer than 5 relapses in the 10 years. Those with a high relapse rate had statistically significantly more global volume loss, nGM loss, and nWM loss than those with a low relapse rate, he said. There were no significant differences in vCSF.

The researchers found that MRI changes correlated with the degree of EDSS and relapse rate. "This suggests that long-term brain atrophy change may provide a valuable outcome of longstanding disability and progression in patients with MS," they conclude.

A separate multicenter study used a semiautomated MRI approach to measure cervical cord atrophy in 333 MS patients and 143 control subjects.

The study showed that cervical cord cross-sectional area differs significantly among the different forms of MS. "In line with previous studies, cervical cord atrophy is not present in patients with clinically isolated syndromes and relapsing-remitting MS, while it is present and extremely pronounced in patients with the progressive form of the disease," reported Maria Assunta Rocca, MD, from the neuroimaging research unit and the Department of Neurology at the Scientific Institute and University Hospital San Raffaele, Milan, Italy.

Additionally, compared with patients with secondary-progressive MS, those with benign MS tended to have "a relative preservation of cord integrity," she said.

The MRI findings were significantly associated with the EDSS disability scale, suggesting that "this measure should be included at least in trials involving patients with progressive forms of the disease," said Dr. Rocca.

MRI measurement of brain and spinal cord atrophy is not clinically applicable at the moment, but might be a useful tool for monitoring treatment in the future, said Douglas Arnold, MD, a neurologist specializing in MS at the Montreal Neurological Institute and Hospital, McGill University, in Montreal, Quebec, Canada, who was comoderator of the session.

"What the drug companies are looking for is a medication to stop neurodegeneration. I think the single most representative and most reliable biomarker of that would be atrophy. I think all this holds potential, but those treatments are still not here," he told Medscape Medical News.

Using atrophy as a measure of treatment response is a complicated proposal, because a reduction or even arrest of atrophy might not be immediately apparent, he said.

After starting treatment, "you'd have to wait for all the damaged tissue that's already there to be cleared out before you could actually see the real effect — and that has a long lag. Axons take time to degenerate, and myelin takes years, probably, to completely degenerate and to be phagocytized and completely disappear. Even if you were to stop the inflammation today, your atrophy rate might slow over several years before it actually was reduced to the normal aging rate."

The speakers and the commentator have disclosed no relevant financial relationships.

International Society for Magnetic Resonance in Medicine (ISMRM) 19th Annual Meeting and Exhibition: Abstract 403, presented May 11, 2011; Abstract 606, presented May 12, 2011.


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