Abstract
Fatigue is among the most common, yet least understood, symptoms of multiple sclerosis (MS) [1·]. It can profoundly disrupt the occupational and social functioning of patients, and is recognized as a criterion for MS disability by the Social Security Administration. Most approaches to fatigue assessment can be classified as either self-report scales or performance-based measures of motor or cognitive output. During the clinical management of fatigue, it is important to consider the role of other MS symptoms on fatigue, as well as that of non—MS-related medical conditions. Management of fatigue in MS often entails both pharmacologic and behavioral components. This article reviews recent developments in the assessment, treatment, and pathogenesis of MS fatigue.
Similar content being viewed by others
References and Recommended Reading
Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and Multiple Sclerosis: Evidence-based Management Strategies for Fatigue in Multiple Sclerosis. Washington DC: Paralyzed Veterans of America, 1998. This is a comprehensive review of current knowledge on fatigue in multiple sclerosis. The manual summarizes an evaluation and treatment algorithm and provides directions for future research.
Freal J, Kraft G, Coryell J: Symptomatic fatigue in multiple sclerosis. Arch Phys Med Rehabil 1984, 65:135–138.
Murray T: Amantadine therapy for fatigue in multiple sclerosis. Can J Neural Sci 1985, 12:251–254.
Krupp L, Alvarez L, LaRocca N, Scheinberg L: Clinical characteristics of fatigue in multiple sclerosis. Arch Neurol 1988, 45:435–437.
Schwartz CE, Coulthard Morris L, Zeng Q: Psychosocial correlates of fatigue in multiple sclerosis. Arch Phys Med Rehabil 1996, 77:165–170.
Vercoulen J, Hommes O, Swanink C, et al.: The measurement of fatigue in patients with multiple sclerosis: a multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects. Arch Neurol 1996, 53:642–649.
Provinciali L, Ceravolo M, Bartolini M, et al.: A multidimensional assessment of multiple sclerosis: relationships between disability domains. Acta Neurol Scand 1999, 100:156–162.
Code of Federal Regulations, Title 20—Employees’ Benefits, Chapter III - Social Security Administration, Part 404 - Federal Old-Age, Survivors and Disability Insurance (1950-), Subpart P - Determining Disability and Blindness, Appendix 1 to Subpart P of Part 404 — Listing of Impairments, Part A.
Fisk J, Pontefract A, Ritvo P, et al.: The impact of fatigue on patients with multiple sclerosis. Can J Neural Sci 1994, 21:9–14.
Iriarte J, Katsamakis G, De Castro P: The fatigue descriptive scale (FDS): a useful tool to evaluate fatigue in multiple sclerosis. Mult Scler 1999, 5:10–16.
Krupp L, La Rocca N, Muirnash J, Steinberg A: The fatigue severity scale-application to patients with multiple sclerosis and systemic lupus-erythematosus. Arch Neurol 1989, 46:1121–1123.
Belza B, Henke C, Yelin E, et al.: Correlates of fatigue in older adults with rheumatoid arthritis. Nurs Res 1993, 42:93–99.
Smets E, Garssen B, Bonke B, De Haes J: The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 1995, 39:315–325.
Schwartz J, Jandorf L, Krupp LB: The measurement of fatigue: a new scale. J Psychosom Res 1993, 37:753–762.
Chalder T, Berelowitz G, Pawlikowska T, et al.: Development of a fatigue scale. J Psychosom Res 1993, 37:147–153.
Sheean GL, Murray NM, Rothwell JC, et al.: An open-labeled clinical and electrophysiological study of 3,4 diaminopyridine in the treatment of fatigue in multiple sclerosis. Brain 1998, 121:967–975. This study demonstrates how treatment with 3,4 diaminopyridine differentially affects a performance-based measure of fatigue (electrophysiologic test) from a self-report assessment of fatigue (fatigue severity scale).
Rammohan K, Rosenberg JH, Pollak CP, et al.: Modafinil-efficacy and safety for the treatment of fatigue in patients with multiple sclerosis [abstract]. Neurology 2000, 54(suppl 3):A24.
Fischer J, La Rocca N, Miller D, et al.: Recent developments in the assessment of quality of life in multiple sclerosis (MS). Mult Scler 1999, 5:251–259.
Ware J, Kosinski M, Keller S: SF-36 Physical and Mental Health Summary Scales: A User’s Manual. Boston: The Health Institute, New England Medical Center; 1994.
McNair D, Lorr M, Droppleman L: Profile of mood states. San Diego: Educational and Industrial Testing Service; 1992.
Taylor RR, Jason LA, Torres A: Fatigue rating scales: an empirical comparison. Psychol Med 2000, 30:849–856. The relative strengths of two fatigue scales are evaluated in control patients and individuals with chronic fatigue syndrome with respect to their psychometric properties and correlation to measures of quality of life using the SF-36.
Schwid S, Thornton C, Pandya S, et al.: Quantitative assessment of motor fatigue and strength in MS. Neurology 1999, 53:743–750. Strength and motor fatigue can be measured reliably in multiple sclerosis with a protocol involving sustained contractions, repetitive contractions, and ambulation.
Djaldetti R, Ziv I, Achiron A, Melamed E: Fatigue in multiple sclerosis compared with chronic fatigue syndrome: a quantitative assessment. Neurology 1996, 46:632–635.
Sharma K, Kent-Braun J, Mynhier M: Evidence of an abnormal intramuscular component of fatigue in multiple sclerosis. Muscle Nerve 1995, 18:1403–1411.
Sheean G, Murray NM, Rothwell J, et al.: An electrophysiological study of the mechanism of fatigue in multiple sclerosis. Brain 1997, 120:299–315.
Kent-Braun J, Sharma K, Miller R, Weiner M: Postexercise phosphocreatine resynthesis is slowed in multiple sclerosis. Muscle Nerve 1994, 17:835–841.
Latash M, Kalugina E, Nicholas J, et al.: Myogenic and central neruogenic factors in fatigue in multiple sclerosis. Mult Scler 1996, 1:236–241.
Schubert M, Wohlfarth K, Rollnick J, Dengler R: Walking and fatigue in multiple sclerosis: the role of the corticospinal system. Muscle Nerve 1998, 21:1068–1070.
Kujala P, Portin R, Reconsuo A, Ruutiainen J: Attention related performance in two cognitively different subgroups of patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 1995, 59:77–82.
Krupp LB, Elkins LE: Fatigue and declines in cognitive functioning in multiple sclerosis. Neurology 2000, 55:934–939. Cognitive fatigue, defined as a decline in cognitive performance during a single testing session, can be identified in multiple sclerosis and distinguished from the pattern observed in control patients.
Logan G, Klapp S: Automatizing alphabet arithmetic: I. Is extended practice necessary to produce automaticity? J Exp Psychol: Learning, Memory, Cognition 1991, 17:179–195.
Johnson SK, Lange G, DeLuca J, et al.: The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol 1997, 4:145–153.
Paul RH, Beatty WW, Schneider R, et al.: Impairments of attention in individuals with multiple sclerosis. Mult Scler 1998, 4:433–439.
Heilman K, Watson R: Fatigue. Neurol Network Comm 1997, 1:283–287.
Newsholme EA, Blomstrand E: The plasma level of some amino acids and physical and mental fatigue. Experientia 1996, 52:413–415.
Bakshi R, Miletich R, Henschel K, et al.: Fatigue in multiple sclerosis: cross-sectional correlation with brain MRI findings in 71 patients. Neurology 1999, 53:1151–1153. An extensive analysis of magentic resonance imaging (MRI) measures in 71 multiple sclerosis (MS) patients with and without fatigue concludes that MRI disease topography and severity do not explain MS fatigue.
Mainero C, Faroni J, Gasperini C, et al.: Fatigue and magnetic resonance imaging activity in multiple sclerosis. J Neurol 1999, 246:454–458.
Van Der Werf S, Jongen P, Lycklama a Nijeholt G, et al.: Fatigue in multiple sclerosis: inter-relations between fatigue complaints, cerebral MRI abnormalities and neurological disability. J Neurol Sci 1998, 160:164–170.
Moller A, Wiedemann G, Rohde U, et al.: Correlates of cognitive impairment and depressive mood disorder in multiple sclerosis. Acta Psychiatrica Scand, 1994, 89:117–121.
Roelcke U, Kappos L, Lechner-Scott J, et al.: Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 1997, 48:1566–1571.
Quesada J, Talpaz M, Rios A, et al.: Clinical toxicity of interferons in cancer patients: a review. J Clin Oncol 1986, 4:234–243.
Neilley L, Goodlin D, Goodkin D, Hauser S: Side effect profile of interferon-beta 1b in MS results of an open label trial. Neurology 1996, 46:552–554.
Jones T, Wadler S, Hupart K: Endocrine-mediated mechanisms of fatigue during treatment with interferon-alpha. Semin Oncol 1998, 25(suppl 1):54–63.
Martinez-Caceres E, Rio J, Barrau M, et al.: Amelioration of flulike symptoms at the onset of interferon B-1b therapy in multiple sclerosis by low-dose oral steroids is related to a decrease in interleukine-6 induction. Ann Neurol 1998, 44:682–685.
Bakshi R, Shaikh ZA, Miletich RS, et al.: Fatigue in multiple sclerosis and its relationship to depression and neurologic disability. Mult Scler 2000, 6:181–185.
Kroencke DC, Lynch SG, Denney DR: Fatigue in multiple sclerosis: relationship to depression, disability, and disease pattern. Mult Scler 2000, 6:131–136.
Pepper C, Krupp LB, Friedberg F: A comparison of psychiatric characteristics in chronic fatigue syndrome, multiple sclerosis and depression. J Neuropsychiatry Clin Neurosci 1993, 5:200–205.
Krupp LB, Coyle PK, Doscher C, et al.: Fatigue therapy in multiple sclerosis: results of a double blind, randomized, parallel trial of amantadine, pemoline, and placebo. Neurology 1995, 45:1956–1961.
Weinshenker BG, Penman M, Bass B, et al.: A double-blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis. Neurology 1992, 42:1468–1471.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Krupp, L.B., Christodoulou, C. Fatigue in multiple sclerosis. Curr Neurol Neurosci Rep 1, 294–298 (2001). https://doi.org/10.1007/s11910-001-0033-7
Issue Date:
DOI: https://doi.org/10.1007/s11910-001-0033-7