SLEEP DISTURBANCES AND ITS RELATION TO FATIGUE IN PATIENTS WITH MULTIPLE SCLEROSIS

Abstract
Fatigue is the most disabling symptom of multiple sclerosis (MS). Two years ago we published our findings demonstrating a relationship between fatigue in MS and sleep disruptions. The following article is a brief review of all the papers published since then on the subject and our future plans to further investigate this relationship. The handful papers published on the subject over the last 2 years have shown no daytime sleepiness in mild to moderate MS patients both subjectively and objectively. No papers were published on nocturnal sleep in MS. There was one paper looking at the hypothalamic-pituitary-adrenal (HPA) axis dysfunction in the pathogenesis of MS fatigue which may mean that the HPA axis dysfunction is a common pathway for both MS fatigue and sleep disorders. At our center we are looking at the relationship of fatigue in MS and insomnia and also MS fatigue and obstructive sleep apnea syndrome.

Key words
Fatigue, multiple sclerosis, sleep, insomnia, obstructive sleep apnea

Bibliografía del artículo
1. Reder AT, Antel JP. Clinical spectrum of multiple sclerosis. Neurol Clin 1983; 1(3):573-99.
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(11):1956-61.
3. Krupp LB, Pollina DA. Mechanisms and management of fatigue in progressive neurological disorders. Curr Opin Neurol 1996; 9(6):456-60.
4. 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(1):10-6.
5. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14(6):540-5.
6. Attarian HP, Brown KM, Duntley SP, Carter JD, Cross AH. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch Neurol 2004; 61(4):525-8.
7. Frauscher B, Egg R, Brandauer E, et al. Daytime sleepiness is not increased in mild to moderate multiple sclerosis: a pupillographic study. Sleep Med 2005; 6(6):543-7.
8. Danker-Hopfe H, Kraemer S, Dorn H, Schmidt A, Ehlert I, Herrmann WM. Time-of-day variations in different measures of sleepiness (MSLT, pupillography, and SSS) and their interrelations. Psychophysiology 2001; 38(5):828-35.
9. Wilhelm B, Wilhelm H, Ludtke H, Streicher P, Adler M. Pupillographic assessment of sleepiness in sleep-deprived healthy subjects. Sleep 1998; 21(3):258-65.
10. Mathiowetz VG, Finlayson ML, Matuska KM, Chen HY, Luo P. Randomized controlled trial of an energy conservation course for persons with multiple sclerosis. Mult Scler 2005; 11(5):592-601.
11. Strober LB, Arnett PA. An examination of four models predicting fatigue in multiple sclerosis. Arch Clin Neuropsychol 2005; 20(5):631-46.
12. Alarcia R, Ara JR, Martin J, Bertol V, Bestue M. Importance and factors related to chronic fatigue in multiple sclerosis. Neurologia 2005; 20(2):77-84.
13. Alarcia R, Ara JR, Martin J, et al. Sleep disorders in multiple sclerosis. Neurologia 2004; 19(10):704-9.
14. Merkelbach S, Schulz H. What have fatigue and sleepiness in common? J Sleep Res 2006; 15(1):105-6.
15. Gottschalk M, Kumpfel T, Flachenecker P, et al. Fatigue and regulation of the hypothalamo-pituitary-adrenal axis in multiple sclerosis. Arch Neurol 2005; 62(2):277-80.
16. Buckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab 2005; 90(5):3106-14.
17. Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG. Orexins in the regulation of the hypothalamic-pituitary-adrenal axis. Pharmacol Rev 2006; 58(1):46-57.
18. Kato T, Kanbayashi T, Yamamoto K, et al. Hypersomnia and low CSF hypocretin-1 (orexin-A) concentration in a patient with multiple sclerosis showing bilateral hypothalamic lesions. Intern Med 2003; 42(8):743-5.
19. Stankoff B, Waubant E, Confavreux C, et al. Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology 2005; 64(7):1139-43.