MS Speaks

Fatigue, Leg Dysfunction Predict Multiple Sclerosis Progression

Both associated with subsequent conversion to secondary progressive MS

by Kristina Fiore
Associate Editor, MedPage Today

BOSTON -- Fatigue and lower limb problems predicted conversion from relapsing-remitting to secondary progressive MS in the long run, researchers reported.
In an analysis of data from the New York State Multiple Sclerosis Consortium (NYSMSC), those two factors were the only significant predictors of disease progression over 5 years in patients who had the disease for many years, according to Bianca Weinstock-Guttman, MD, of the University at Buffalo in New York, and colleagues. The research will be presented at the American Academy of Neurology meeting here in April.

"We have to inquire on patients' perceived symptoms and not rely only on neurologic exam," Weinstock-Guttman told MedPage Today. "The presence of these symptoms should raise increased concerns, and [physicians should] consider more appropriate therapies, such as change to a more efficacious disease-modifying therapy. They should also re-emphasize active exercise, improved diet, the importance of sleep, and a general [attention] to wellness."

Traditional factors shown to be predictive of a higher risk of disease conversion in MS include older age at onset, high frequency of relapses, and male gender. To assess additional factors that may help in predicting disease progression, Weinstock-Guttman and colleagues assessed data from the NYSMSC, which included 155 patients who at baseline had relapsing-remitting disease, were at least 50 years old, and had a disease duration of at least 15 years.

After a median 5 years of study enrollment, about 30% of patients had progressed to secondary progressive MS, and at that point had been living with the disease for an average of 22 years.

Those who converted to SPMS were older at study enrollment (age 54.8 versus 52.1, P=0.01) and had higher Expanded Disability Status Scale (EDSS) scores at both baseline (3.5 versus 2.6, P<0.001) and year 5 (5.6 versus 3.0, P<0.001).
But in further analyses that controlled for age, disease duration, and EDSS scores, the only two factors that remained significantly associated with disease conversion were lower limb problems (OR 3.0, P<0.001) and fatigue (OR 4.2, P=0.004) at baseline.

In both cases, a larger proportion of those who progressed had lower limb problems (53.2% versus 21.5%) and some degree of fatigue (91.5% versus 68.2%) at baseline.

The researchers noted that fatigue and lower limb problems were strongly correlated (P=0.001).

"While the precise cause of fatigue in patients with MS has yet to be fully elucidated, it is most likely a result of the underlying complex inflammatory and neurodegenerative processes that characterize MS," Weinstock-Guttman said. "These include sequelae from MS itself -- demyelination, axonal injury, and inflammatory response -- in addition to other factors such as depression and sleep disturbances.
"Therefore, fatigue may be a more sensitive indicator of the extent of CNS injury, similar to patient-reported lower extremity dysfunction, which may not be fully assessed or gauged during a short neurological exam."

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The study was supported by the National Multiple Sclerosis Society.

The authors disclosed no financial relationships with industry.