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Professor and Vice Chair (Clinical Affairs)
Director, MS Comprehensive Care Center
Department of Neurology
Stony Brook University Hospital
Stony Brook, New York
Patricia K. Coyle, MD, FAAN, FANA, has disclosed that she has received consulting fees from Accordant, Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Genentech/Roche, GlaxoSmithKline, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio; funds for research support from Alkermes, Corrona, Genentech/Roche, MedDay, and NINDS; and fees for non-CME/CE services from Biogen and Janssen.
Fatigue can be defined as an overwhelming sense of tiredness out of proportion to activity. It is one of the most common, disabling—yet invisible—symptoms of the disease. Indeed, approximately 80% of individuals with multiple sclerosis (MS) will experience fatigue, and they often consider it to be the major symptom of their disease. This symptom can be multifactorial and cover several aspects of care, including cognitive/mental, emotional, and physical components. Fatigue can also be a feature of the MS prodrome and can occur at any time point in the course of MS. Fatigue is not determined by clinical phenotype or level of disability, but it is a major cause of inability to work and can dramatically impair quality of life.
Quality Improvement in MS: Fatigue
In 2021, the Quality Improvement Initiative of the American Academy of Neurology defined 6 measures for quality improvement in MS. One of those measures was fatigue screening and follow-up. Because fatigue is an “invisible” symptom, it is typically assessed through patient-reported outcomes. There are standardized patient-reported outcomes for fatigue, including the Modified Fatigue Impact Scale, Fatigue Severity Scale, Fatigue Impact Questionnaire-Relapsing MS, and a visual analog fatigue scale.
Fatigue Types and Comorbidities
The impact of fatigue can range from poorer cognitive performance to inability to perform physical tasks or even hold a job. When caring for an individual with MS who reports fatigue, it is important for healthcare professionals to remember that there are different types of fatigue, including normal fatigue or fatigue due to a comorbid sleep disorder (eg, insomnia, rapid eye movement sleep behavior disorder, sleep-disordered breathing, narcolepsy, restless legs syndrome) or poor sleep hygiene. Fatigue may also be associated with comorbid depression or comorbid medical disorders, such as thyroid disease or anemia, or due to an adverse event of medication, for example, from disease-modifying therapies and supportive therapies (eg, analgesics, anticholinergics) that can contribute to fatigue. Fatigue from physical disability requiring greater effort/energy to ambulate and move around can be seen in those patients who are baseline disabled. Finally, there is primary MS fatigue. Primary MS fatigue typically occurs daily, often peaks in early afternoon, and is often heat/humidity sensitive. For some patients, primary MS fatigue may be constant. However, the etiology of primary MS fatigue is not yet clear and may reflect damage to certain central nervous system areas, brain circuit disruptions, or sequelae of central or peripheral nervous system inflammatory factors.
It is important to remember that individuals with MS may have more than one type of fatigue. However, regardless of the type of fatigue, each needs to be individually recognized and addressed for optimal outcomes.
Ultimately, the evaluation of fatigue should also include confirmation of its significant impact on the patient. This can be documented by questioning the patient and checking with his or her family, friends, and employer. It may be reasonable to also perform selected blood work (thyroid-stimulating hormone, complete blood count); evaluate for depression, sleep disorders, and pharmacologic adverse events (as noted above); and assess current disability/mobility status and required effort.
Treatment for the fatigue of MS should not solely rely on writing a prescription. The recent phase II TRIUMPHANT trial found no benefit vs placebo for 3 commonly prescribed treatments for alleviating fatigue in MS (amantadine, methylphenidate, modafinil). Not only was there no greater therapeutic benefit from these agents, but they were also associated with more frequent adverse events. Currently, treatment for the fatigue of MS should involve a multimodal approach. In addition to possible pharmacologic remedies, treatment can involve environmental manipulation such as cooling techniques or changing work location, programmed rest periods or even brief naps, exercise (aerobic, resistance training, yoga), use of appropriate assistive devices for energy conservation, cognitive behavioral therapy, and relaxation therapy. Ongoing studies are examining the potential benefits of neurostimulation in reducing MS fatigue.
Fatigue is a critically important symptom of MS to recognize. Clinicians should employ a checklist approach to identify the patient’s type(s) of fatigue. Of importance, the treatment plan for reducing fatigue must be a multimodality approach, with ongoing monitoring and reassessment.
How do you manage fatigue in persons with MS? Answer the polling question and join the conversation by posting in the discussion section.