Fatigue in Multiple Sclerosis

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Multiple sclerosis is a chronic, debilitating, inflammatory, and neurodegenerative disease of the central nervous system. There is no cure for the disease, and its management includes use of symptomatic agents and diseasemodifying therapies to reduce and/or prevent relapses and disease progression. Fatigue affects up to 90% of MS patients and can significantly impair function, quality of life, and interaction with family and friends. The common causes of fatigue and effective interventions and treatments are reviewed in this article.

Section snippets

Definition

There is no universally accepted definition of fatigue in MS patients. One common definition describes a “subjective lack of physical and/or mental energy, perceived by the individual or caregiver to interfere with usual and desired activities.” Some other definitions include “pathologic exhaustion,” “reversible motor and cognitive impairment with reduced motivation and desire to rest,” and “difficulty with initiation of or sustaining voluntary activities that does not correlate with muscle

Impact of fatigue

Fatigue in the MS patient can have profound negative effects. Patients frequently need to nap, take frequent breaks, or sleep early. This may interfere with family activities, cause avoidance of the outdoors due to fatiguing effects of heat, or lead to an inability to participate in events that require prolonged physical effort. Social activities with friends and family are difficult to plan, as some days MS patients may awaken with an overwhelming sense of fatigue that cannot be alleviated

Assessment tools

The Fatigue Severity Score (FSS), the Fatigue Impact Scale (FIS), and the Modified Fatigue Impact Scale (MFIS) are the most commonly used scales for fatigue assessment in MS patients.18 The FSS is composed of 9 items that assess perceived fatigue.19 Subjects are asked to assign a number from 1 (strongly disagree) to 7 (strongly agree) stating their agreement with each statement.4 Responses are summed and averaged, with a score of 4 or more indicating significant fatigue.20

The FIS has been

Pathogenesis—primary factors

When evaluating the pathogenesis of fatigue in MS, it is important to distinguish primary fatigue from secondary fatigue. Primary fatigue is a result of the disease process, and secondary fatigue results from medications or disease-related manifestations.24 Due to the multimodal aspect of fatigue in MS, it is difficult to differentiate primary fatigue from secondary fatigue, as several factors contribute to fatigue manifestation.

There are several theories on the pathogenesis of fatigue, with

Pathogenesis—secondary factors

There are several additional factors that may worsen fatigue for patients with MS (Box 1). Thermosensitivity is common in people with MS, leading to instability and delay in signal conduction in demyelinated nerves. Increased body temperature induces conduction block, resulting in deterioration of neurologic function, which is known as the Uhthoff phenomenon. MS fatigue secondary to heat sensitivity differs from that in normal healthy adults (NHAs) in that heat intolerance causes difficulty in

Prevention

After ruling out primary and/or secondary causes of fatigue and deciding on treatment, it is important that the clinician's approach to the treatment of fatigue be global, including pharmacologic and nonpharmacologic approaches. Nonpharmacologic approaches include local cooling devices, energy management strategies (spacing out activities, performing strenuous activities during periods of increased energy stores), behavioral/lifestyle modifications (good sleep hygiene, limiting alcohol intake,

Summary

In summary, MS-related fatigue can be a severe problem causing interference with home and vocational activities. There are multiple factors that can contribute to fatigue in MS, and it is important for the patient, family, and clinician to be aware of potential confounders that may worsen fatigue. Clearer understanding about the etiology of fatigue is necessary. Additional larger, randomized, clinical trials are needed to evaluate etiology, pathophysiology, and both pharmacologic and

Acknowledgment

The author thanks Dr. Ian B. Maitin for his editorial comments on the manuscript.

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    Conflict of Interest: The author is a paid consultant for Biogen Idec, EMD Serono, and Teva Pharmaceuticals.

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