Skip to main content

Advertisement

Log in

Fatigue in multiple sclerosis: A rational approach to evaluation and treatment

  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

With the publication of the Multiple Sclerosis Council Guideline on the management of multiple sclerosis (MS) fatigue, there has been increased appreciation for the role fatigue can play in MS. Secondary fatigue is fatigue caused by other etiologies than those directly related to MS. Once these causes are ruled out, fatigue is related to MS. Secondary MS-related fatigue comes as result of the symptoms of MS that drain energy. Once secondary MS causes are ruled out, then the patient is deemed as having primary MS fatigue. Fatigue management is both nonpharmacologic and pharmacologic. Occupational therapists are the major allied health providers that address the role fatigue plays in MS patients. Over the past two decades, numerous clinical trials have been conducted on drugs for treating MS-related fatigue. Of these agents, amantadine has been studied for the longest period, and has shown efficacy in about one third of patients with MS-related fatigue on several commonly used scales. Two randomized trials of the central nervous system stimulant pemoline have yielded unimpressive results; efficacy was seen at higher doses but coupled with an unacceptable risk of adverse events. The wake-promoting agent modafinil is the only agent to show efficacy compared with placebo on the Fatigue Severity Scale, a measure that is highly resistant to impulse “answering” and is thus viewed as one of the most difficult scales on which to show benefit. This article reviews fatigue in MS and proposes a rational strategy for evaluation and management of this most common MS symptom.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Multiple Sclerosis Council for Clinical Practice Guidelines: Fatigue and Multiple Sclerosis. Washington, DC: Paralyzed Veterans of America; 1998.

    Google Scholar 

  2. 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.

    PubMed  CAS  Google Scholar 

  3. Pepper CM, Krupp LB, Friedberg F, et al.: A comparison of neuropsychiatric characteristics in chronic fatigue syndrome, multiple sclerosis, and major depression. J Neuropsychiatry Clin Neurosci 1993, 5:200–205.

    PubMed  CAS  Google Scholar 

  4. The Canadian MS Research Group: A randomized controlled trial of amantadine in fatigue associated with muliptle sclerosis. Can J Neurol Sci 1987, 14:273–278.

    Google Scholar 

  5. Beck AT, Ward CH, Mendelson N, et al.: An inventory for measuring depression. Arch Gen Psychiatry 1961, 4:561–571.

    PubMed  CAS  Google Scholar 

  6. Tachibana N, Howard RS, Hirsch NP, et al.: Sleep problems in MS. Eur Neurol 1994, 34:320–323.

    PubMed  CAS  Google Scholar 

  7. Ferini-Strambi L, Filippi M, Martinelli V, et al.: Nocturnal sleep study in MS: correlations with clinical and brain magnetic resonance imaging findings. J Neurol Sci 1994, 125:1940–1947.

    Google Scholar 

  8. Antonijevic IA, Steiger A: Depression-like changes of the sleep-EEG during high dose corticosteroid treatment in patients with Multiple Sclerosis. Psychoneuroendocrinology 28:780–795.

  9. Taphoorn MJ, Van Someren E, Snoek FJ, et al.: Fatigue, sleep disturbances and circadian rhythm in multiple sclerosis. J Neurol 1993, 240:446–448.

    Article  PubMed  CAS  Google Scholar 

  10. Krupp LB, Jandorf L, Coyle PK, et al.: Sleep disturbance in chronic fatigue syndrome. J Psychosom Res 1993, 37:325–332.

    Article  PubMed  CAS  Google Scholar 

  11. Fogdell A, Hillert J, Sachs C, et al.: The multiple sclerosis-and narcolepsy-associated HLA class II haplotype incudes the DRB5*0101 allele. Tissue Antigens 1995, 46:333–336.

    PubMed  CAS  Google Scholar 

  12. Younger DS, Pedley TA, Thorpy MJ: Multiple sclerosis and narcolepsy: possible similar genetic susceptibility. Neurology 1991, 41:447–448.

    PubMed  CAS  Google Scholar 

  13. Sandyk R: The pineal gland, cataplexy, and multiple sclerosis. Int J Neurosci 1995, 83:153–163.

    PubMed  CAS  Google Scholar 

  14. Olgiata R, Burgunder JM, Mumenthaler M: Increased energy cost of walking in multiple sclerosis: effect of spacticity, ataxia, and weakness. Arch Phys Med Rehabil 1988, 69:846–849.

    Google Scholar 

  15. Roelck U, Kappos L, Lechner-Scott J: Reduced glucose metabolism in the frontal cortex and basal ganglion of multiple sclerosis patients with fatigue: an 18F-flurodeoxyglucose positron tomography study. Neurology 1997, 48:1566–1571.

    Google Scholar 

  16. Sandroni P, Walker WC, Starr C: Fatigue in patients with multiple sclerosis: motor pathway conduction and event-related potentials. Arch Neurol 1992, 49:517–524.

    PubMed  CAS  Google Scholar 

  17. Johns MW: A new method for measuring daytime sleepiness: theEpworth sleepiness scale. Sleep 1991, 14:560–565.

    Google Scholar 

  18. Rammohan KW, Rosenberg JH, Lynn DJ, et al.: Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two-centre phase 2 study. J Neurol Neurosurg Psychiatry 2002, 72:179–183. Important study.

    Article  PubMed  CAS  Google Scholar 

  19. Glossary of Terms — O. Organic Brain Injury Resource Network. http://www.tr.wou.edu/tbi/O.htm>. Accessed October 29, 2004.

  20. Murray TJ: Amantadine therapy for fatigue in multiple sclerosis. Can J Neurol Sci 1985, 12:251–254.

    PubMed  CAS  Google Scholar 

  21. Cohen RA, Fisher M: Amantadine treatment of fatigue associated with multiple sclerosis. Arch Neurol 1989, 46:676–680.

    PubMed  CAS  Google Scholar 

  22. 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.

    PubMed  CAS  Google Scholar 

  23. Cylert® (pemoline) package insert. Chicago, IL: Abbott Laboratories; June 1999.

  24. 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.

    PubMed  CAS  Google Scholar 

  25. US Modafinil in Narcolepsy Multicenter Study Group: Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 2000, 54:1166–1175.

    Google Scholar 

  26. Lin JS, Hou Y, Jouvet M: Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Proc Natl Acad Sci USA 1996, 93:14128–14133.

    Article  PubMed  CAS  Google Scholar 

  27. Scammell TE, Estabrooke IV, McCarthy MT, et al.: Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci 2000, 20:8620–8628.

    PubMed  CAS  Google Scholar 

  28. Zifko UA, Rupp M, Schwartz S, et al.: Modafinil in treatment of fatigue in multiple sclerosis. Results of an open label study. J Neurol 2002, 249:983–987.

    Article  PubMed  CAS  Google Scholar 

  29. Pigeau R, Naitoh P, Buguet A, et al.: Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature. J Sleep Res 1995, 4:212–228.

    PubMed  Google Scholar 

  30. Arnulf I, Homeyer P, Garma L, et al.: Modafinil in obstructive sleep apnea-hypopnea syndrome: a pilot study in 6 patients. Respiration 1997, 64:159–161.

    Article  PubMed  CAS  Google Scholar 

  31. Beusterien KM, Rogers AE, Walsleben JA, et al.: Health-related quality of life effects of modafinil for treatment of narcolepsy. Sleep 1999, 22:757–765.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosenberg, J.H., Shafor, R. Fatigue in multiple sclerosis: A rational approach to evaluation and treatment. Curr Neurol Neurosci Rep 5, 140–146 (2005). https://doi.org/10.1007/s11910-005-0012-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11910-005-0012-5

Keywords

Navigation