Advanced Reading: Fatigue and Multiple Sclerosis

Summary

Fatigue is the most common symptom of multiple sclerosis (MS), affecting at least two thirds of patients. Furthermore, nearly half of patients describe MS fatigue as the most disabling feature of the disease. Fatigue clearly impairs the quality of life of patients with MS. The cause of MS fatigue is unknown; the phenomenon cannot be adequately explained by physical disability, although it is frequently associated with depression. Factors thought to contribute to MS fatigue include dysfunction of premotor, limbic, basal ganglia, or hypothalamic areas; disturbances of the neuroendocrine axis; changes in serotonin pathways or other neurotransmitters; and dysimmunity. Neuroimaging studies have revealed a correlation between MS fatigue and hypometabolism or reduced activation of frontal and subcortical gray matter areas of the brain. Several pharmacologic and nonpharmacologic measures play a role in the treatment of MS fatigue. A multifactorial approach to treatment is recommended.

Definition, Impact, and Diagnosis

MS is the most common cause of progressive neurologic disability in young adults and affects approximately 350,000 people in the United States. Fatigue associated with MS is an abnormal, generalized lack of energy that significantly limits physical and/or mental ability regardless of the degree of effort or level of neurologic disability.^[1-3] Fatigue is the most common symptom of MS and one of the most disabling aspects of the disease. More than two thirds of patients with MS experience significant fatigue,^[1-7] and nearly half describe it as the most debilitating feature of the disease.^[6-9] Fatigue independently contributes to impairments in quality of life of patients with MS^{[5, 10-12]} through a reduction in energy and endurance, and by adversely affecting mood, outlook, and coping ability.^[13,14] Fatigue affects both motor and cognitive ability. Cognitive fatigue is the slowing of mental function while performing repetitive tasks.^[15] Additional evidence of the impact of MS fatigue is the negative effect on employment^[13]; indeed, the United States Social Security Administration recognizes the impairment resulting from fatigue as a factor contributing to disability in patients with MS.

The diagnosis of MS fatigue includes the presence of fatigue symptoms for at least 50% of days for more than 6 weeks (Multiple Sclerosis Clinical Practice Guideline: Fatigue and Multiple Sclerosis: Evidence-Based Management Strategies for Fatigue in Multiple Sclerosis. Washington, DC: Paralyzed Veterans Association; 1999.). This criterion is useful to distinguish MS fatigue from other MS symptoms. Reduced energy, malaise, motor weakness during sustained activity, and difficulty maintaining concentration are common features of MS fatigue. It is important to question patients about fatigue because the symptom may not be reported voluntarily. This underreporting may occur if the patient has accepted fatigue as an inevitable and untreatable consequence of a chronic disease or if specific physical complaints are more obvious.

The differential diagnosis of MS fatigue includes depression, physical disability, thyroid disorders, and side effects of medications such as antispasmodics and immunosuppressive agents. Self-report questionnaires such as the Fatigue Severity Scale^[16] may be useful in the diagnosis of MS fatigue and as a surrogate outcome measure.