89/4/9 : Multiple Sclerosis) : MS.

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1 89/6/13 : 89/4/9 : 1389 /113 / : Multiple Sclerosis) :.. (MS MS. 60 MS 120 ( ) MS 1388 : (PSQI). (FSS). MS.(P = 0/002) MS :.(P<0/05) MS :.. MS (Circadian). (PSQI) :.(FSS).(1). (SCN). najafi@med.mui.ac.ir :

2 MS.(3 8) (9-10) MS.(11) (Quality of life) QoL MS :. MS..(12). 3 MS Taphoorn.(13) MS 16 Soorensen (14) Ferini-.(15) MS Tachibana (16) Strambi (17). MS Tachibana (2).(3-4). (Jet Lag) (Shift work sleep disorders) Delayed sleep phase. syndrome Advanced sleep. phase syndrome 6-9 Non hour sleep wake syndrome. Irregular sleep wake pattern.(5) Multiple Sclerosis) Demyelinative (MS /5.(6).(7) 702

3 . (Expanded disability scale score) EDSS EDSS 2. FSS (Fatigue severity scale). (19) (19) PSQI (Pittsburgh sleep quality index).(20) (Cronbach's Alpha = 0/83) MS (17) 15 Attarian MS 15 MS 15 MS.(18) MS MS ( ) MS 18 Relapsing secondary progressive/remitting. 2 MS. - MS Secondary progressive (Relapsing/remitting) 703

4 2/8± 0/9 ( ). 2/5± 0/7 ( ) FSS 22/5± 7/4 49/9± 8/2 PSQI.(P< 0/0001) 7/9± 4/5 4/5± 2/4 5/9± 3/6.(1 ) (P<0/0001) Advanced ) (sleep phase syndrome (Delayed sleep phase syndrome) Irregular sleep wake ) MS (pattern 11/7) 7 ( 6/7) 4 48/3) 29 ( 33/3) 20 (. ( 3/3) 2 ( 8/3) 5 ( 18/3) 11 ( ( 70) /7) 7 ( 1/7) 1 76/7) 46 ( 10) 6 ( (.(1 ) (P = 0/002) (PSQI) MS. 4 PSQI..(19) 2 MS PSQI FSS EDSS. PSQI 2 χ. SPSS Independent sample t-test (version 16, SPSS Inc., Chicago, IL) MS. ( ) 33± 8/8 12 ( 80) 48. ( 20) EDSS. 704

5 3/6± 1/8 7± 1/6.(2 ) (P< 0/0001). MS (14 18) 11/2± 3/9 12/2± 4/8 5± 1/4.(P< 0/0001) 5± 2/4 MS PSQI 3 7/4± 4/3 6/5± 0/7 9/8±.(P = 0/015) 5/1± 3/1 7/7± 2/4 6 MS (PSQI) (FSS) (EDSS).1 P value > 0/05 32± 9/1 31± 8/8 35± 8/3 ( ) > 0/05 48 ( 80) 48 ( 80) 48 ( 80) - 0/115 < 0/ /5± 2/4 2/5± 0/7 5/9± 3/6 2/8± 0/9 7/9± 4/5 EDSS PSQI 50 ٤٦ 45 ٤٢ ٢٩ ٢٠ ١١ 10 ٤ ٧ ٧ ٥ ٦ 5 ٢ ١

6 14 12 ١٢/٢ ١١/٢ 10 ٩/٨ PSQI ٧/٧ ٧ ٦/٥ ٧/٤ ٦ ٥/١ ٥ ٥ ٣/٦ 2 0 PSQI MS (Basal ganglia).(21).(22) MS Attarian MS (2) Advanced sleep ) (phase syndrome (Delayed sleep phase syndrome) Irregular sleep wake ) (pattern. MS MS.(P = 0/002) MS.(P< 0/05) 706

7 Demyelinative MRI CRDs. Functional MRI MS. MS..(23) MS. MS (Delayed sleep phase syndrome) MS Taphoorn.(18) MS 16.(14) MS. CRDs. MS. ) Demyelinative ( MS.(14) References Ibata Y, Okamura H, Tanaka M, Tamada Y, Hayashi S, Iijima N, et al. Functional morphology of the suprachiasmatic nucleus. Front Neuroendocrinol 1999; 20(3): American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic and coding manual. 2 nd ed. Westchester: American Academy of Sleep 3. Sack RL, Auckley D, Auger RR, Carskadon MA, Wright KP, Vitiello MV, et al. Circadian rhythm sleep disorders: part I, basic principles, shift work and jet lag disorders. An American Acad

8 emy of Sleep Medicine review. Sleep 2007; 30(11): Sack RL, Auckley D, Auger RR, Carskadon MA, Wright KP, Vitiello MV, et al. Circadian rhythm sleep disorders: part II, advanced sleep phase disorder, delayed sleep phase disorder, freerunning disorder, and irregular sleep-wake rhythm. An American Academy of Sleep Medicine review. Sleep 2007; 30(11): National institute of Health. Sleep-Information about sleep. [Online]. [cited 2007 Jun 28]; Available from: URL: 6. Multiple Sclerosis Society America. Frequently asked questions. [Online]. [cited 2009 Feb 24]; Available from: URL: 7. Debouverie M, Pittion-Vouyovitch S, Louis S, Guillemin F. Natural history of multiple sclerosis in a population-based cohort. Eur J Neurol 2008; 15(9): Scammell TE, Estabrooke IV, McCarthy MT, Chemelli RM, Yanagisawa M, Miller MS, et al. Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci 2000; 20(22): Khan F, McPhail T, Brand C, Turner-Stokes L, Kilpatrick T. Multiple sclerosis: disability profile and quality of life in an Australian community cohort. Int J Rehabil Res 2006; 29(2): Iriarte J, Subira ML, Castro P. Modalities of fatigue in multiple sclerosis: correlation with clinical and biological factors. Mult Scler 2000; 6(2): Turpin KV, Carroll LJ, Cassidy JD, Hader WJ. Deterioration in the health-related quality of life of persons with multiple sclerosis: the possible warning signs. Mult Scler 2007; 13(8): Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and multiple sclerosis: evidence-based management strategies for fatigue in multiple sclerosis. Washington, DC: The Council; Clark CM, Fleming JA, Li D, Oger J, Klonoff H, Paty D. Sleep disturbance, depression, and lesion site in patients with multiple sclerosis. Arch Neurol 1992; 49(6): Taphoorn MJ, van Someren E, Snoek FJ, Strijers RL, Swaab DF, Visscher F, et al. Fatigue, sleep disturbances and circadian rhythm in multiple sclerosis. J Neurol 1993; 240(7): Soorensen KV, Alslev T, Christensen SE, Jensen NB, Orskov H. CSF somatostatin in multiple sclerosis: reversible loss of diurnal oscillation in relapses. Neurology 1987; 37(6): Ferini-Strambi L, Filippi M, Martinelli V, Oldani A, Rovaris M, Zucconi M, et al. Nocturnal sleep study in multiple sclerosis: correlations with clinical and brain magnetic resonance imaging findings. J Neurol Sci 1994; 125(2): Tachibana N, Howard RS, Hirsch NP, Miller DH, Moseley IF, Fish D. Sleep problems in multiple sclerosis. Eur Neurol 1994; 34(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): Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989; 46(10): Buysse DJ, Reynolds CF, III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28(2): Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet 2004; 363(9413): Bakshi R, Shaikh ZA, Miletich RS, Czarnecki D, Dmochowski J, Henschel K, et al. Fatigue in multiple sclerosis and its relationship to depression and neurologic disability. Mult Scler 2000; 6(3): Brass SD, Duquette P, Proulx-Therrien J, Auerbach S. Sleep disorders in patients with multiple sclerosis. Sleep Med Rev 2010; 14(2):

9 Journal of Isfahan Medical School Original Article Vol 28, No 113, 1 st week, January 2011 Received: Accepted: The Study of Circadian Rhythms Disorder and Its Relationship with Chronic Fatigue in Multiple Sclerosis in Compare with Control Group Abstract Mohammad Reza Najafi MD 1, Masoud Etemadifar MD 2, Sepehr Haghighi 3, Amir Hadi Maghzi 3, Mojtaba Akbari 4 Background: Circadian rhythm disorders (CRDs) are one of the manifestations of all types of sleep disorders in Multiple Sclerosis (MS) patients. Knowing about these problems and rationale approach to them can increase the health level and treat these patients. The aim of this study was to determine the frequency of circadian rhythm disorders in MS patients in compare with control group and ascertain its association with chronic fatigability. Methods: The case-control study was held on 120 Multiple sclerosis patients and 60 healthy people (as control group) in MS Clinic of Al-Zahra Hospital in Isfahan in The questionnaires of PSQI, FSS and EDSS was given to patients and for assessing the circadian rhythm disorders, the PSQI questionnaire was given to control group too. All the findings were analyzed in SPSS software. Finding: The amount of circadian rhythm disorders in MS patients was significantly higher than control group (P = 0.002). In this manner, these kind of circadian rhythm disorders in patients with severe fatigue was significantly higher than patients with mild fatigue (P < 0.05). Conclusion: This study showed that the rate of circadian rhythm disorders in MS patients with severe and mild fatigue was higher than control group. Increased distribution of these groups of disorders may empower the more susceptibility of biologic clock, which regulates the circadian rhythm, in the course of MS disease. More studies are required for confirmation of anatomic relationship between location of demyelinative plaque and types of sleep disorders. Key words: Circadian rhythm disorders, Multiple sclerosis, Chronic fatigability, PSQI questionnaire, FSS questionnaire. 1 Associate Professor, Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. 2 Professor, Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. 3 Medical Student, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. 4 Epidemiologist, Vice Chancellor of Research OfFice, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Corresponding Author: Mohammad Reza Najafi MD, najafi@med.mui.ac.ir 709