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  • Updated 07.21.2023
  • Released 08.31.2009
  • Expires For CME 07.21.2026

Fatigue in multiple sclerosis



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 (49). 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 (49). 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 (18). Alan Stevenson, a 19th-century Scottish poet, scholar, and lighthouse keeper, described episodes of “drowsiness” as well as tiredness in his writings (49).

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” (37). 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” (20).

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