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Understanding the Patient Factors Linked to Fatigue in Multiple Sclerosis


The advent of both new diagnostic criteria and treatments have necessitated a reevaluation of fatigue among individuals who have multiple sclerosis, investigators say.

Fatigue remains a common symptom with multiple sclerosis (MS), and a new study provides an updated assessment of patient demographics that predispose to fatigue, owing to both new diagnostic criteria and new disease-modifying drugs.

This Norwegian cross-sectional cohort study, published in Multiple Sclerosis Journal - Experimental, Translational and Clinical, found that female patients with a higher level of disability, as well as higher rates of anxiety, depression, and excessive daytime sleepiness, are more likely to report fatigue as a symptom of their MS.

The Fatigue Scale for Motor and Cognitive Functions gauged fatigue levels, anxiety and depression were evaluated via the Hospital Anxiety and Depression Scale, and the Epworth Sleepiness Scale was used to measure daytime sleepiness. All were self-reported by participants whose mean (SD) age was 52 (13) years. Disability level also was evaluated with the Kurtzke Expanded Disability Status Scale (EDSS).

Overall, the median (interquartile range [IQR]) disease duration among the cohort was 16 (IQR, 8-25) years, and the median EDSS was 2.5 (IQR, 1.5-3.0). Eighty-one percent of patients also had measurable levels of fatigue, with women having a higher prevalence compared with men: 83% vs 78% (P = .02). The most common form of MS was relapsing-remitting MS (RR-MS), which was seen in 83%.

“To our knowledge there have been no larger, population-based studies on the prevalence of fatigue in MS for almost 20 years,” the investigators noted. “Our objectives were to determine the prevalence of fatigue in the current MS population in Norway, and to assess its relation to sex, age, phenotype, disease severity and duration.”

In addition, older age and increasing disease severity were shown to contribute to a higher prevalence of fatigue—although an independent association remained for just sex and disease severity following multivariate analyses.

A total of 2512 patients were mailed questionnaires when the study began in December 2017, and the response rate was 64% at the end of the study period in June 2019. Data covered patients with MS from Oslo, Buskerud, and Telemark counties in Norway. Seventy percent were female, and most were 50 years or older.

Analyses also showed:

  • 67% had severe fatigue, 19% moderate fatigue, and 15% mild fatigue
  • 77% had cognitive fatigue and 82% had motor fatigue
  • 86% of patients 50 years and older reported fatigue vs 75% of patients younger than 50 (P < . 001)
  • 88% of patients with progressive MS reported fatigue vs 80% who had RR-MS (P = .03)
  • Patients with progressive MS were older vs those who had RR-MS: 63 (10) vs 50 (13) years (P < . 001)
  • Severe fatigue was more prevalent in participants with an EDSS above 3.0 vs 0.0 to 3.0: 66% vs 48% (P < . 001)
  • Patients reporting fatigue had higher prevalences of anxiety, depression, and daytime sleepiness (all P < .001) vs those not reporting fatigue:
    • Anxiety: 20% vs 3.3%
    • Depression: 11% vs 0%
    • Daytime sleepiness: 42% vs 11%

“We expected the prevalence to be lower compared to previous studies because the course of MS seem to be milder, at least during the last decade, partly due to improvements in diagnostics and treatment,” the authors said. They attribute their higher rates to the older mean age of their participants and that more diagnoses are made earlier and at an older age.

Possible influences on their results include that the questionnaires were mailed, fatigue levels could have affected individuals’ willingness to participate, and analysis of the interaction between disease modifying treatment and fatigue was not possible. Additional studies are planned.


Broch L, Simonson CS, Flemmen HØ. High prevalence of fatigue in contemporary patients with multiple sclerosis. Mult Scler J Exp Transl Clin. Published online March 18, 2021. doi:10.1177/2055217321999826

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