Pauline Anderson

March 16, 2017

Patients with relapsing-remitting multiple sclerosis (RRMS) who report fatigue and lower-limb problems are more likely to progress to secondary progressive MS (SPMS) within 5 years, a new study shows.

The results suggest that patient-reported function may be more enlightening than physician-initiated measurements in predicting which patients with MS will worsen, said researcher Bianca Weinstock-Guttman, MD, professor of neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, New York, director of the Jacobs MS Center for Treatment and Research, and executive director of the New York State MS Consortium.

American Academy of Neurology 2017 Annual Meeting (AAN). Abstract P1.370. Presented April 23, 2017..

Validated Questionnaire

The study included 155 patients aged 50 years and older in the New York State Multiple Sclerosis Consortium who had had RRMS for at least 15 years and attended three or more follow-up visits.

Researchers gathered patient-reported outcomes from the validated Lifeware questionnaire. This included information on fatigue and lower-extremity dysfunction. Limb problems could involve issues such as weakness, spasms, or difficulty climbing stairs or bending, said Dr Weinstock-Guttman.

Five years after study enrollment, 30.3% of patients had progressed to SPMS. Those who converted were older (54.8 years vs 52.1 years; P = .01) and had a higher Expanded Disability Status Scale (EDSS) score at baseline (3.5 vs 2.6; P < .001) and at the end of the study (5.6 vs 3.0; P < .001). The EDSS ranges from 0 to 10, with higher scores representing greater disability.

Compared with patients who didn't progress, those who did were more likely to report lower-limb problems at baseline (53.2% vs 21.5%; odds ratio [OR], 3.0; P < .001). They were also more likely to report fatigue (91.5% vs 68.2%; OR, 4.2; P = .004).

This was after adjustment for age, disease duration, and EDSS score.

The study results highlight the importance of querying patients about fatigue and leg problems, said Dr Weinstock-Guttman. "Asking about and evaluating patient-reported data is very, very important" because with use of standard office measurements, "we may not always be able to identify underlying problems."

For example, with the EDSS, "you may see a very minimal difference or none at all, but the patient is telling you that after a long walk she is starting to drag one of her legs, or that she used to be able to run and now can't run," she said. "There are certain things that we are not able to evaluate very well on our exam."

Some evidence suggests that more aggressive treatment approaches for patients suspected of being prone to disease conversion may help prevent this worsening, said Dr Weinstock-Guttman.

Intriguing Finding

Asked to comment on the new findings, Barbara S. Giesser, MD, professor, neurology and medical director, Marilyn Hilton Multiple Sclerosis Achievement Center, University of California at Los Angeles, and fellow of the AAN, said it's not surprising that patients who converted to SPMS were initially more disabled and had lower-limb involvement.

"These parameters are commonly associated with increased disability," she said.

As for fatigue, it has been reported to be more prevalent in patients with SPMS and is also more pronounced in those with greater mobility impairments, noted Dr Giesser.

"However, fatigue is reported as a symptom in up to 90% of persons with MS, and in and of itself does not necessarily correlate with physical disability. For example, people with severe fatigue may not have a concomitant degree of severe physical disability."

So it's not clear from this small study sample if fatigue itself predicts conversion to SPMS or only in association with lower-limb impairment, said Dr Giesser.

"This is an intriguing finding and more study is warranted," she concluded.

Also commenting for Medscape Medical News is Jonathan L. Carter, MD, Department of Neurology, Mayo Clinic, Scottsdale, Arizona, who has done research on MS.  He, too, found the association of fatigue with disease progression interesting.

"Fatigue is multifactorial, so teasing out why fatigue predicts later progression may be challenging, but it does provide a further avenue to study," said Dr Carter. "Since validated fatigue self-rating tools have been developed for MS, this is something that could be screened for routinely and might help identify a group at greater risk of progression."

Like Dr Giesser, Dr Carter didn't find the correlation between lower-extremity problems and disease progression particularly novel, given that the tool used to measure the change (EDSS) heavily depends upon ambulatory ability across the range of scores.

The study was supported by a grant from the National Multiple Sclerosis Society.

American Academy of Neurology (AAN) 2017 Annual Meeting. Abstract 461. To be presented April 24, 2017.

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