Fatigue in multiple sclerosis

Rinu Abraham MD (

Dr. Abraham of the University of Chicago is currently being funded by Biogen for her advanced clinical MS fellowship.

Anthony T Reder MD, editor. (

Dr. Reder of the University of Chicago received honorariums from Bayer, Biogen Idec, Caremark Rx, Genentech, Genzyme, Novartis, Mallinckrodt, Mylan, Serono, and Teva-Marion for service on advisory boards and as a consultant as well as stock options from NKMax America for advisory work.

Originally released August 31, 2009; last updated November 1, 2019; expires November 1, 2022


Fatigue is the most common and debilitating symptom affecting persons with multiple sclerosis. It is one of the most difficult symptoms to treat due to its subjective nature, complex pathophysiology, and need for a multidisciplinary approach to treatment. Moreover, other conditions that disproportionately affect persons with multiple sclerosis, including depression and several sleep disorders, may contribute to or be mistaken for the symptom of fatigue, making it difficult to diagnose and treat appropriately. Physicians treating persons with multiple sclerosis should be familiar with the common presentations and definitions of multiple sclerosis-related fatigue, currently proposed causes of fatigue, and approach to treatment. In this article, the author provides a review of the common presentations, causes, evaluation, and treatment of multiple sclerosis-related fatigue.

Historical note and terminology

For centuries, physicians and medical historians have studied multiple sclerosis and its symptoms (Murray 2005). Historical accounts of these symptoms, including fatigue, are well-documented. In one of the first documented cases of multiple sclerosis in the medical literature, Charles Prosper Ollivier d'Angers, a 19th century medical practitioner, described a 20-year-old patient who felt “tired and languid” prior to experiencing his first multiple sclerosis relapse (Murray 2005). Personal accounts from one of the earliest documented patients with multiple sclerosis, Augustus d'Este, grandson of King George III, chronicled his relapses and symptoms from 1822 to 1848. In his writings, he described symptoms reminiscent of fatigue in the context of endurance and loss of strength (d'Este and Firth 1948). Alan Stevenson, a 19th century Scottish poet, scholar, and lighthouse keeper, described episodes of “drowsiness” as well as tiredness in his writings (Murray 2005).

Despite early recognition, the complexity and subjective nature of fatigue has precluded a unified definition to date. Common definitions include a “sense of exhaustion,” “lack of energy,” or “tiredness” (Krupp et al 1988). The Fatigue Guidelines Development Panel of the Multiple Sclerosis Council for Clinical Practice Guidelines defined fatigue as “a subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual or desired activity” (Fatigue Guidelines Development Panel of the Multiple Sclerosis Council for Clinical Practice Guidelines 1998).

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