Gender issues in multiple sclerosis: An update

Women's Health

Volumn 6, Issue 6, 2010, Pages 797-820

  Jobin, Céline ^a   Larochelle, Catherine ^a   Parpal, Hélène ^a   Coyle, Patricia K ^b   Duquette, Pierre ^a  

^a NOTRE DAME HOSPITAL   (Canada)

^b STONY BROOK UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

disease course; gender; genetics; hormonal factors; incidence; multiple sclerosis; pregnancy; prevalence; psychosocial issues; treatment

Indexed keywords

BETA1A INTERFERON; ESTROGEN; GLATIRAMER; LEPTIN; NATALIZUMAB; ORAL CONTRACEPTIVE AGENT; PLACEBO; PROLACTIN; SEX HORMONE; TESTOSTERONE;

ANATOMICAL VARIATION; AUTOIMMUNE DISEASE; CAREGIVER BURDEN; CLINICAL FEATURE; CLINICAL TRIAL; COGNITIVE DEFECT; COMORBIDITY; CONGENITAL MALFORMATION; COPING BEHAVIOR; DELAYED DIAGNOSIS; DISEASE COURSE; DNA METHYLATION; DRUG MECHANISM; EMPLOYMENT DISCRIMINATION; ENVIRONMENTAL FACTOR; FEMALE; FINANCIAL MANAGEMENT; GENETIC COUNSELING; GENETIC EPIGENESIS; GENETIC MARKER; HEALTH ASSESSMENT QUESTIONNAIRE; HEALTH CARE COST; HORMONE ACTION; HORMONE SUBSTITUTION; HUMAN; INCIDENCE; MALIGNANT NEOPLASTIC DISEASE; MARRIAGE; MENARCHE; MENOPAUSE; MENSTRUAL CYCLE; MENTAL DISEASE; MICROCHIMERISM; MULTIPLE SCLEROSIS; NEUROANATOMY; NEUROIMAGING; NEUROPROTECTION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; ONSET AGE; ORAL CONTRACEPTION; PATHOGENESIS; PATIENT ATTITUDE; PREGNANCY OUTCOME; PREVALENCE; PROGNOSIS; PROLACTIN RELEASE; PUBERTY; QUALITY OF LIFE; RESTLESS LEGS SYNDROME; REVIEW; SEX DIFFERENCE; SEX DIFFERENTIATION; SEXUAL DYSFUNCTION; SEXUAL SATISFACTION; SEXUALITY; SLEEP DISORDER; SOCIAL PSYCHOLOGY; SOCIAL SUPPORT; TERMINAL CARE; VITAMIN D DEFICIENCY;

COMORBIDITY; FEMALE; HUMANS; MALE; MULTIPLE SCLEROSIS; PREGNANCY; PROGNOSIS; RISK FACTORS; SEX DISTRIBUTION; WOMEN'S HEALTH;

EID: 78649962118     PISSN: 17455057     EISSN: 17455065     Source Type: Journal    
DOI: 10.2217/whe.10.69     Document Type: Review

References (314)

1. Coyle PK: Gender issues. Neurol. Clin. 23(1), 39-60, v-vi (2005).
2. Ebers GC: Environmental factors and multiple sclerosis. Lancet Neurol. 7(3), 268-277 (2008).
3. Trapp BD, Nave KA: Multiple sclerosis: an immune or neurodegenerative disorder? Annu. Rev. Neurosci. 31, 247-269 (2008).
4. Alonso A, Hernan MA: Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 71(2), 129-135 (2008).
5. Grimaldi LM, Palmeri B, Salemi G et al.: High prevalence and fast rising incidence of multiple sclerosis in Caltanissetta, Sicily, southern Italy. Neuroepidemiology 28(1), 28-32 (2007).
6. Orton SM, Ramagopalan SV, Brocklebank DM et al.: Effect of immigration on multiple sclerosis sex ratio in Canada: the Canadian Collaborative Study. J. Neurol. Neurosurg. Psychiatry (2009).
7. Granieri E, Casetta I, Govoni V et al.: The increasing incidence and prevalence of MS in a Sardinian province. Neurology 55(6), 842-848 (2000).
8. Pugliatti M, Sotgiu S, Solinas G et al.: Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk. Acta Neurol. Scand. 103(1), 20-26 (2001).
9. Pugliatti M, Cossu P, Sotgiu S, Rosati G, Riise T: Clustering of multiple sclerosis, age of onset and gender in Sardinia. J. Neurol. Sci. 286(1-2), 6-13 (2009).
10. Celius EG, Vandvik B: Multiple sclerosis in Oslo, Norway: prevalence on 1 January 1995 and incidence over a 25-year period. Eur. J. Neurol. 8(5), 463-469 (2001).
11. Midgard R, Riise T, Svanes C, Kvale G, Nyland H: Incidence of multiple sclerosis in More and Romsdal, Norway from 1950 to 1991. An age-period-cohort analysis. Brain 119(Pt 1), 203-211 (1996).
12. Sarasoja T, Wikstrom J, Paltamaa J, Hakama M, Sumelahti ML: Occurrence of multiple sclerosis in central Finland: a regional and temporal comparison during 30 years. Acta Neurol. Scand. 110(5), 331-336 (2004).
13. Sloka JS, Pryse-Phillips WE, Stefanelli M: Incidence and prevalence of multiple sclerosis in Newfoundland and Labrador. Can. J. Neurol. Sci. 32(1), 37-42 (2005). (Pubitemid 40363575)
14. Dahl OP, Aarseth JH, Myhr KM, Nyland H, Midgard R: Multiple sclerosis in Nord- Trondelag County, Norway: a prevalence and incidence study. Acta Neurol. Scand. 109(6), 378-384 (2004).
15. Granieri E, Economou NT, De Gennaro R et al.: Multiple sclerosis in the province of Ferrara: evidence for an increasing trend. J. Neurol. 254(12), 1642-1648 (2007).
16. Grytten N, Glad SB, Aarseth JH et al.: A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway. Neurology 66(2), 182-186 (2006).
17. Sumelahti ML, Tienari PJ, Wikstrom J, Palo J, Hakama M: Increasing prevalence of multiple sclerosis in Finland. Acta Neurol. Scand. 103(3), 153-158 (2001).
18. Koch-Henriksen N, Bronnum-Hansen H, Hyllested K: Incidence of multiple sclerosis in Denmark 1948-1982: a descriptive nationwide study. Neuroepidemiology 11(1), 1-10 (1992).
19. Nicoletti A, Patti F, Lo Fermo S et al.: Possible increasing risk of multiple sclerosis in Catania, Sicily. Neurology 65(8), 1259-1263 (2005).
20. Wynn DR, Rodriguez M, OFallon WM, Kurland LT: A reappraisal of the epidemiology of multiple sclerosis in Olmsted County, Minnesota. Neurology 40(5), 780-786 (1990).
21. Barnett MH, Williams DB, Day S, Macaskill P, McLeod JG: Progressive increase in incidence and prevalence of multiple sclerosis in Newcastle, Australia: a 35-year study. J. Neurol. Sci. 213(1-2), 1-6 (2003).
22. Wallin MT, Page WF, Kurtzke JF: Multiple sclerosis in US veterans of the Vietnam era and later military service: race, sex, and geography. Ann. Neurol. 55(1), 65-71 (2004).
23. Hirst C, Ingram G, Pickersgill T et al.: Increasing prevalence and incidence of multiple sclerosis in South East Wales. J. Neurol. Neurosurg. Psychiatry 80(4), 386-391 (2009).
24. Debouverie M, Pittion-Vouyovitch S, Louis S, Roederer T, Guillemin F: Increasing incidence of multiple sclerosis among women in Lorraine, Eastern France. Mult. Scler. 13(8), 962-967 (2007).
25. Koch-Henriksen N: The Danish Multiple Sclerosis Registry: a 50-year follow-up. Mult. Scler. 5(4), 293-296 (1999).
26. Larsen JP, Kvaale G, Riise T, Nyland H, Aarli JA: An increase in the incidence of multiple sclerosis in western Norway. Acta Neurol. Scand. 70(2), 96-103 (1984).
27. Rosati G: The prevalence of multiple sclerosis in the world: an update. Neurol. Sci. 22(2), 117-139 (2001).
28. Orton SM, Herrera BM, Yee IM et al.: Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol. 5(11), 932-936 (2006).
29. Talley CL: The emergence of multiple sclerosis, 1870-1950: a puzzle of historical epidemiology. Perspect. Biol. Med. 48(3), 383-395 (2005).
30. Confavreux C, Aimard G, Devic M: Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain 103(2), 281-300 (1980).
31. Noonan CW, Kathman SJ, White MC: Prevalence estimates for MS in the United States and evidence of an increasing trend for women. Neurology 58(1), 136-138 (2002).
32. Hernan MA, Olek MJ, Ascherio A: Geographic variation of MS incidence in two prospective studies of US women. Neurology 53(8), 1711-1718 (1999).
33. Cutter G, Yadavalli R, Marrie RA: Changes in the sex ratio over time in multiple sclerosis. Neurology 68, A162 (2007).
34. Simmons RD, Hall CA, Gleeson P et al.: Prevalence survey of multiple sclerosis in the Australian Capital Territory. Intern. Med. J. 31(3), 161-167 (2001).
35. Houzen H, Niino M, Kikuchi S et al.: The prevalence and clinical characteristics of MS in northern Japan. J. Neurol. Sci. 211(1-2), 49-53 (2003).
36. Cristiano E, Patrucco L, Rojas JI: A systematic review of the epidemiology of multiple sclerosis in South America. Eur. J. Neurol. 15(12), 1273-1278 (2008).
37. Callegaro D, Goldbaum M, Morais L et al.: The prevalence of multiple sclerosis in the city of Sao Paulo, Brazil, 1997. Acta Neurol. Scand. 104(4), 208-213 (2001).
38. Grimaldi LM, Salemi G, Grimaldi G et al.: High incidence and increasing prevalence of MS in Enna (Sicily), southern Italy. Neurology 57(10), 1891-1893 (2001).
39. Phadke JG, Downie AW: Epidemiology of multiple sclerosis in the north-east (Grampian region) of Scotland - an update. J. Epidemiol. Community Health 41(1), 5-13 (1987).
40. Celius EG, Smestad C: Change in sex ratio, disease course and age at diagnosis in Oslo MS patients through seven decades. Acta Neurol. Scand. Suppl. 189, 27-29 (2009).
41. McLeod JG, Hammond SR, Hallpike JF: Epidemiology of multiple sclerosis in Australia. With NSW and SA survey results. Med. J. Aust. 160(3), 117-122 (1994).
42. Kurtzke JF, Beebe GW, Norman JE Jr: Epidemiology of multiple sclerosis in US veterans: 1. Race, sex, and geographic distribution. Neurology 29(9 Pt 1), 1228-1235 (1979).
43. Visscher BR, Detels R, Coulson AH, Malmgren RM, Dudley JP: Latitude, migration, and the prevalence of multiple sclerosis. Am. J. Epidemiol. 106(6), 470-475 (1977).
44. Baum HM, Rothschild BB: The incidence and prevalence of reported multiple sclerosis. Ann. Neurol. 10(5), 420-428 (1981).
45. Miller DH, Hammond SR, McLeod JG, Purdie G, Skegg DC: Multiple sclerosis in Australia and New Zealand: are the determinants genetic or environmental? J. Neurol. Neurosurg. Psychiatry 53(10), 903-905 (1990).
46. Kurtzke JF: Multiple sclerosis in time and space - geographic clues to cause. J. Neurovirol. 6(Suppl. 2), S134-S140 (2000).
47. Minden SL, Marder WD, Harrold LN: Multiple sclerosis: a statistical portrait. National Multiple Sclerosis Society, Cambridge, UK, 183 (1993).
48. Sadovnick AD, Ebers GC: Epidemiology of multiple sclerosis: a critical overview. Can. J. Neurol. Sci. 20(1), 17-29 (1993).
49. Wu MV, Manoli DS, Fraser EJ et al.: Estrogen masculinizes neural pathways and sex-specific behaviors. Cell 139(1), 61-72 (2009).
50. Gabory A, Attig L, Junien C: Sexual dimorphism in environmental epigenetic programming. Mol. Cell. Endocrinol. 304(1-2), 8-18 (2009).
51. Nicot A: Gender and sex hormones in multiple sclerosis pathology and therapy. Front. Biosci. 14, 4477-4515 (2009).
52. Gold SM, Voskuhl RR: Estrogen and testosterone therapies in multiple sclerosis. Prog. Brain Res. 175, 239-251 (2009).
53. Kelly VM, Nelson LM, Chakravarty EF: Obstetric outcomes in women with multiple sclerosis and epilepsy. Neurology 73(22), 1831-1836 (2009).
54. Gregg C: Pregnancy, prolactin and white matter regeneration. J. Neurol. Sci. 285(1-2), 22-27 (2009).
55. Nociti V, Frisullo G, Tartaglione T et al.: Multiple sclerosis attacks triggered by hyperprolactinemia. J. Neurooncol. 98(3), 407-409 (2009).
56. Munger KL, Chitnis T, Ascherio A: Body size and risk of MS in two cohorts of US women. Neurology 73(19), 1543-1550 (2009).
57. Bialek M, Zaremba P, Borowicz KK, Czuczwar SJ: Neuroprotective role of testosterone in the nervous system. Pol. J. Pharmacol. 56(5), 509-518 (2004).
58. Garcia-Segura LM, Azcoitia I, DonCarlos LL: Neuroprotection by estradiol. Prog. Neurobiol. 63(1), 29-60 (2001).
59. Sribnick EA, Wingrave JM, Matzelle DD, Ray SK, Banik NL: Estrogen as a neuroprotective agent in the treatment of spinal cord injury. Ann. N. Y. Acad. Sci. 993, 125-133; discussion 159-160 (2003).
60. Sicotte NL, Tandon V, Klutch R et al.: Testosterone Treatment in Multiple Sclerosis A Pilot Study. Arch. Neurol. 64(5), 683-688 (2007).
61. Handel AE, Ebers GC, Ramagopalan SV: Epigenetics: molecular mechanisms and implications for disease. Trends Mol. Med. 16(1), 7-16 (2010).
62. Kantarci OH, Barcellos LF, Atkinson EJ et al.: Men transmit MS more often to their children vs women: the Carter effect. Neurology 67(2), 305-310 (2006).
63. Nielsen NM, Westergaard T, Rostgaard K et al.: Familial risk of multiple sclerosis: a nationwide cohort study. Am. J. Epidemiol. 162(8), 774-778 (2005).
64. Hemminki K, Sundquist K, Li X: Familial risks for main neurological diseases in siblings based on hospitalizations in Sweden. Twin Res. Hum. Genet. 9(4), 580-586 (2006). (Pubitemid 46381689)
65. Sadovnick AD: European Charcot Foundation Lecture: the natural history of multiple sclerosis and gender. J. Neurol. Sci. 286(1-2), 1-5 (2009).
66. Okuda DT, Srinivasan R, Oksenberg JR et al.: Genotype-phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures. Brain 132(Pt 1), 250-259 (2009).
67. Celius EG, Harbo HF, Egeland T et al.: Sex and age at diagnosis are correlated with the HLA-DR2, DQ6 haplotype in multiple sclerosis. J. Neurol. Sci. 178(2), 132-135 (2000).
68. Kantarci OH, Hebrink DD, Achenbach SJ et al.: CD95 polymorphisms are associated with susceptibility to MS in women. A population-based study of CD95 and CD95L in MS. J. Neuroimmunol. 146(1-2), 162-170 (2004).
69. Kantarci OH, Hebrink DD, Schaefer-Klein J et al.: Interferon g allelic variants: sex-biased multiple sclerosis susceptibility and gene expression. Arch. Neurol. 65(3), 349-357 (2008).
70. Borchers AT, Naguwa SM, Keen CL, Gershwin ME: The implications of autoimmunity and pregnancy. J. Autoimmun. (2009).
71. Sadovnick AD: Genetic counselling and genetic screening for Alzheimers disease and other dementias. Can. J. Neurol. Sci. 28(Suppl. 1), S52-S55 (2001).
72. Goodin DS: The causal cascade to multiple sclerosis: a model for MS pathogenesis. PLoS One 4(2), e4565 (2009).
73. Hedstrom AK, Baarnhielm M, Olsson T, Alfredsson L: Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis. Neurology 73(9), 696-701 (2009).
74. Rodriguez Regal A, del Campo Amigo M, Paz-Esquete J et al.: [A case-control study of the influence of the smoking behaviour in multiple sclerosis]. Neurologia 24(3), 177-180 (2009).
75. Orton SM, Ramagopalan SV, Brocklebank D et al.: Effect of immigration on multiple sclerosis sex ratio in Canada: the Canadian Collaborative Study. J. Neurol. Neurosurg. Psychiatry 81(1), 31-36 (2010).
76. Confavreux C, Vukusic S: [The natural history of multiple sclerosis]. Rev. Prat. 56(12), 1313-1320 (2006).
77. Schwendimann RN, Alekseeva N: Gender issues in multiple sclerosis. Int. Rev. Neurobiol. 79, 377-392 (2007).
78. Voskuhl RR: Gender issues and multiple sclerosis. Curr. Neurol. Neurosci. Rep. 2(3), 277-286 (2002).
79. Hupperts R, Broadley S, Mander A et al.: Patterns of disease in concordant parent-child pairs with multiple sclerosis. Neurology 57(2), 290-295 (2001).
80. Debouverie M, S Pittion-Vouyovitch, Louis S, Guillemin F: Natural history of multiple sclerosis in a population-based cohort. Eur. J. Neurol. 15(9), 916-921 (2008).
81. Confavreux C, Vukusic S, Adeleine P: Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 126(Pt 4), 770-782 (2003).
82. Noseworthy JH, Lucchinetti C, Rodriguez M: Multiple sclerosis. N. Engl. J. Med. 343(13), 938-952 (2000).
83. Van Lambalgen R, Sanders EA, DAmaro J: Sex distribution, age of onset and HLA profiles in two types of multiple sclerosis. A role for sex hormones and microbial infections in the development of autoimmunity? J. Neurol. Sci. 76(1), 13-21 (1986).
84. Bashir K, Whitaker JN: Clinical and laboratory features of primary progressive and secondary progressive MS. Neurology 53(4), 765-771 (1999).
85. Tremlett H, Paty D, Devonshire V: The natural history of primary progressive MS in British Columbia, Canada. Neurology 65(12), 1919-1923 (2005).
86. Confavreux C, Vukusic S: Natural history of multiple sclerosis: a unifying concept. Brain 129(Pt 3), 606-616 (2006). (Pubitemid 43278223)
87. Tremlett H, Paty D, Devonshire V: Disability progression in multiple sclerosis is slower than previously reported. Neurology 66(2), 172-177 (2006).
88. Weinshenker BG, Bass B, Rice GP et al.: The natural history of multiple sclerosis: a geographically based study. I Clinical course and disability. Brain 112 ( Pt 1), 133-146 (1989). (Pubitemid 19056478)
89. Kantarci OH, Weinshenker BG: Natural history of multiple sclerosis. Neurol. Clin. 23(1), 17-38, v (2005).
90. Koch M, Uyttenboogaart M, van Harten A et al.: Factors associated with the risk ofsecondary progression in multiple sclerosis. Mult. Scler. 14(6), 799-803 (2008).
91. Pokryszko-Dragan A, Gruszka E, Bilinska M, Dubik-Jezierzanska M: Secondary progressive multiple sclerosis - clinical course and potential predictive factors. Neurol. Neurochir. Pol., 42(1), 6-11 (2008).
92. Ramsaransing G, Maurits N, Zwanikken C, De Keyser J: Early prediction of a benign course of multiple sclerosis on clinical grounds: a systematic review. Mult. Scler. 7(5), 345-347 (2001).
93. Ramsaransing GS, De Keyser J: Benign course in multiple sclerosis: a review. Acta Neurol. Scand. 113(6), 359-369 (2006).
94. Glad SB, Nyland HI, Aarseth JH, Riise T, Myhr KM: Long-term follow-up of benign multiple sclerosis in Hordaland County, Western Norway. Mult. Scler. 15(8), 942-950 (2009).
95. Tomassini V, Pozzilli C: Sex hormones: a role in the control of multiple sclerosis? Expert Opin. Pharmacother. 7(7), 857-868 (2006).
96. Costelloe L, Thompson A, Walsh C, Tubridy N, Hutchinson M: Long-term clinical relevance of criteria for designating multiple sclerosis as benign after 10 years of disease. J. Neurol. Neurosurg. Psychiatry 79(11), 1245-1248 (2008).
97. Hawkins SA, McDonnell GV: Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J. Neurol. Neurosurg. Psychiatry 67(2), 148-152 (1999).
98. Ramsaransing GS, J De Keyser: Predictive value of clinical characteristics for benign multiple sclerosis. Eur. J. Neurol. 14(8), 885-889 (2007).
99. Sayao AL, Devonshire V, Tremlett H: Longitudinal follow-up of benign multiple sclerosis at 20 years. Neurology 68(7), 496-500 (2007).
100. Polliack ML, Barak Y, Achiron A: Late-onset multiple sclerosis. J. Am. Geriatr. Soc. 49(2), 168-171 (2001).
101. Warnell P: The pain experience of a multiple sclerosis population: a descriptive study. Axone 13(1), 26-28 (1991).
102. Osterberg A, Boivie J, Thuomas KA: Central pain in multiple sclerosis - prevalence and clinical characteristics. Eur. J. Pain. 9(5), 531-542 (2005).
103. Moulin DE, Foley KM, Ebers GC: Pain syndromes in multiple sclerosis. Neurology 38(12), 1830-1834 (1988).
104. Beiske AG, Pedersen ED, Czujko B et al.: Pain and sensory complaints in multiple sclerosis. Eur. J. Neurol. 11(7), 479-482 (2004).
105. Chatel M, Lanteri-Minet M, Lebrun-Frenay C: [Pain in multiple sclerosis]. Rev. Neurol. (Paris) 157(8-9 Pt 2), 1072-1078 (2001).
106. Archibald CJ, McGrath PJ, Ritvo PG et al.: Pain prevalence, severity and impact in a clinic sample of multiple sclerosis patients. Pain 58(1), 89-93 (1994).
107. Chwastiak LA, Gibbons LE, Ehde DM et al.: Fatigue and psychiatric illness in a large community sample of persons with multiple sclerosis. J. Psychosom. Res. 59(5), 291-298 (2005).
108. Bakshi R: Fatigue associated with multiple sclerosis: diagnosis, impact and management. Mult. Scler. 9(3), 219-227 (2003).
109. Koch M, Mostert J, Heerings M, Uyttenboogaart M, De Keyser J: Fatigue, depression and disability accumulation in multiple sclerosis: a cross-sectional study. Eur. J. Neurol. 16(3), 348-352 (2009).
110. Beatty WW, Aupperle RL: Sex differences in cognitive impairment in multiple sclerosis. Clin. Neuropsychol. 16(4), 472-480 (2002).
111. Savettieri G, Messina D, Andreoli V et al.: Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis. J. Neurol. 251(10), 1208-1214 (2004).
112. Rao SM, Leo GJ, Ellington L et al.: Cognitive dysfunction in multiple sclerosis. II Impact on employment and social functioning. Neurology 41(5), 692-696 (1991).
113. Oliveri RL, Cittadella R, Sibilia G et al.: APOE and risk of cognitive impairment in multiple sclerosis. Acta Neurol. Scand. 100(5), 290-295 (1999).
114. Barak Y, Achiron A: Cognitive fatigue in multiple sclerosis: findings from a two-wave screening project. J. Neurol. Sci. 245(1-2), 73-76 (2006).
115. Witte AV, Savli M, Holik A, Kasper S, Lanzenberger R: Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain. Neuroimage 49(2), 1205-1212 (2010).
116. Pozzilli C, Tomassini V, Marinelli F et al.: Gender gap in multiple sclerosis: magnetic resonance imaging evidence. Eur. J. Neurol. 10(1), 95-97 (2003).
117. Weatherby SJ, Mann CL, Davies MB et al.: A pilot study of the relationship between gadolinium-enhancing lesions, gender effect and polymorphisms of antioxidant enzymes in multiple sclerosis. J. Neurol. 247(6), 467-470 (2000).
118. Tomassini V, Pozzilli C: Sex hormones, brain damage and clinical course of Multiple sclerosis. J. Neurol. Sci. 286(1-2), 35-39 (2009).
119. Bansil S, Lee HJ, Jindal S, Holtz CR, Cook SD: Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis. Acta Neurol. Scand. 99(2), 91-94 (1999).
120. Barkhof F, Held U, Simon JH et al.: Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials. Neurology 65(9), 1447-1454 (2005).
121. Antulov R, Weinstock-Guttman B, Cox JL et al.: Gender-related differences in MS: a study of conventional and nonconventional MRI measures. Mult. Scler. 15(3), 345-354 (2009).
122. Li DK, Held U, Petkau J et al.: MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability. Neurology 66(9), 1384-1389 (2006).
123. van Walderveen MA, Lycklama ANGJ, Ader HJ et al.: Hypointense lesions on T1-weighted spin-echo magnetic resonance imaging: relation to clinical characteristics in subgroups of patients with multiple sclerosis. Arch. Neurol. 58(1), 76-81 (2001).
124. Tedeschi G, Lavorgna L, Russo P et al.: Brain atrophy and lesion load in a large population of patients with multiple sclerosis. Neurology 65(2), 280-285 (2005).
125. Kalkers NF, Ameziane N, Bot JC et al.: Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of the disease subtype. Arch. Neurol. 59(10), 1572-1576 (2002).
126. Calabrese M, De Stefano N, Atzori M et al.: Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis. Arch. Neurol. 64(10), 1416-1422 (2007).
127. Pozzilli C, Falaschi P, Mainero C et al.: MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patterns. Neurology 53(3), 622-624 (1999).
128. van Walderveen MA, Tas MW, Barkhof F et al.: Magnetic resonance evaluation of disease activity during pregnancy in multiple sclerosis. Neurology 44(2), 327-329 (1994).
129. Tomassini V, Onesti E, Mainero C et al.: Sex hormones modulate brain damage in multiple sclerosis: MRI evidence. J. Neurol. Neurosurg. Psychiatry 76(2), 272-275 (2005).
130. Whitacre CC: Sex differences in autoimmune disease. Nat. Immunol. 2(9), 777-780 (2001).
131. Dorman JS, Steenkiste AR, Burke JP, Songi M: Type 1 diabetes and multiple sclerosis: together at last. Diabetes Care 26(11), 3192-3193 (2003).
132. Cohen R, Robinson D Jr, Paramore C et al.: Autoimmune disease concomitance among inflammatory bowel disease patients in the United States, 2001-2002. Inflamm. Bowel Dis. 14(6), 738-743 (2008).
133. Weng X, Liu L, Barcellos LF, Allison JE, Herrinton LJ: Clustering of inflammatory bowel disease with immune mediated diseases among members of a Northern Californiamanaged care organization. Am. J. Gastroenterol. 102(7), 1429-1435 (2007).
134. Cooper GS, Bynum ML, Somers EC: Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J. Autoimmun. 33(3-4), 197-207 (2009).
135. Ramagopalan SV, Dyment DA, Valdar W et al.: Autoimmune disease in families with multiple sclerosis: a population-based study. Lancet Neurol. 6(7), 604-610 (2007).
136. Somers EC, Thomas SL, Smeeth L, Hall AJ: Are individuals with an autoimmune disease at higher risk of a second autoimmune disorder? Am. J. Epidemiol. 169(6), 749-755 (2009).
137. Nielsen NM, Westergaard T, Frisch M et al.: Type 1 diabetes and multiple sclerosis: a Danish population-based cohort study. Arch. Neurol. 63(7), 1001-1004 (2006).
138. Nielsen NM, Frisch M, Rostgaard K et al.: Autoimmune diseases in patients with multiple sclerosis and their first-degree relatives: a nationwide cohort study in Denmark. Mult. Scler. 14(6), 823-829 (2008).
139. Shuster EA: Hormonal influences in multiple sclerosis. Curr. Top. Microbiol. Immunol. 318, 267-311 (2008).
140. Caraccio N, Dardano A, Manfredonia F et al.: Long-term follow-up of 106 multiple sclerosis patients undergoing interferon-b 1a or 1b therapy: predictive factors of thyroid disease development and duration. J. Clin. Endocrinol. Metab. 90(7), 4133-4137 (2005).
141. Chen L, Gordon LK: Ocular manifestations of multiple sclerosis. Curr. Opin. Ophthalmol. 16(5), 315-320 (2005).
142. Zein, G, Berta A, Foster CS: Multiple sclerosis-associated uveitis. Ocul. Immunol. Inflamm. 12(2), 137-142 (2004).
143. Raja SC, Jabs DA, Dunn JP et al.: Pars planitis: clinical features and class II HLA associations. Ophthalmology 106(3), 594-599 (1999).
144. Brass SD, Duquette P, Proulx-Therrien J, Auerbach S: Sleep disorders in patients with multiple sclerosis. Sleep Med. Rev. (2009).
145. Manconi M, Ferini-Strambi L, Filippi M et al.: Multicenter case-control study on restless legs syndrome in multiple sclerosis: the REMS study. Sleep 31(7), 944-952 (2008). (Pubitemid 351956933)
146. Manconi M, Rocca MA, Ferini-Strambi L et al.: Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage. Mult. Scler. 14(1), 86-93 (2008).
147. Auger C, Montplaisir J, Duquette P: Increased frequency of restless legs syndrome in a French-Canadian population with multiple sclerosis. Neurology 65(10), 1652-1653 (2005).
148. Manconi M, Fabbrini M, Bonanni E et al.: High prevalence of restless legs syndrome in multiple sclerosis. Eur. J. Neurol. 14(5), 534-539 (2007).
149. Moreira NC, Damasceno RS, Medeiros CA et al.: Restless leg syndrome, sleep quality and fatigue in multiple sclerosis patients. Braz. J. Med. Biol. Res. 41(10), 932-937 (2008).
150. Douay X, Waucquier N, Hautecoeur P, Vermersch P: [High prevalence of restless legs syndrome in multiple sclerosis]. Rev. Neurol. (Paris) 165(2), 194-196 (2009).
151. Gomez-Choco MJ, Iranzo A, Blanco Y et al.: Prevalence of restless legs syndrome and REM sleep behavior disorder in multiple sclerosis. Mult. Scler. 13(6), 805-808 (2007).
152. Galeazzi GM, Ferrari S, Giaroli G et al.: Psychiatric disorders and depression in multiple sclerosis outpatients: impact of disability and interferon b therapy. Neurol. Sci. 26(4), 255-262 (2005).
153. Patten SB, Metz LM, Reimer MA: Biopsychosocial correlates of lifetime major depression in a multiple sclerosis population. Mult. Scler. 6(2), 115-120 (2000).
154. Marrie RA, Horwitz R, Cutter G et al.: The burden of mental comorbidity in multiple sclerosis: frequent, underdiagnosed, and undertreated. Mult. Scler. 15(3), 385-392 (2009).
155. Beal CC, Stuifbergen AK, Brown A: Depression in multiple sclerosis: a longitudinal analysis. Arch. Psychiatr. Nurs. 21(4), 181-191 (2007).
156. Zorzon M, R de Masi, Nasuelli D et al.: Depression and anxiety in multiple sclerosis. A clinical and MRI study in 95 subjects. J. Neurol. 248(5), 416-421 (2001).
157. Arnett PA, Higginson CI, Voss WD et al.: Depressed mood in multiple sclerosis: relationship to capacity-demanding memory and attentional functioning. Neuropsychology 13(3), 434-446 (1999).
158. Moller A, Wiedemann G, Rohde UH: Correlates of cognitive impairment and depressive mood disorder in multiple sclerosis. Acta Psychiatr. Scand. 89(2), 117-121 (1994).
159. Joffe RT, Lippert GP, Gray TA, Sawa G, Horvath Z: Mood disorder and multiple sclerosis. Arch. Neurol. 44(4), 376-378 (1987).
160. Chwastiak L, Ehde DM, Gibbons LE et al.: Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic study of a large community sample. Am. J. Psychiatry 159(11), 1862-1868 (2002).
161. Cetin K, Johnson KL, Ehde DM et al.: Antidepressant use in multiple sclerosis: epidemiologic study of a large community sample. Mult. Scler. 13(8), 1046-1053 (2007).
162. Buchanan RJ, Wang S, Ju H: Gender analyses of nursing home residents with multiple sclerosis. J. Gend. Specif. Med. 6(2), 35-46 (2003).
163. DAlisa S, Miscio G, Baudo S et al.: Depression is the main determinant of quality of life in multiple sclerosis: a classificationregression (CART) study. Disabil. Rehabil. 28(5), 307-314 (2006).
164. Korostil M, Feinstein A: Anxiety disorders and their clinical correlates in multiple sclerosis patients. Mult. Scler. 13(1), 67-72 (2007).
165. Weinshenker BG: Natural history of multiple sclerosis. Ann. Neurol. 36 S6-S11 (1994).
166. Sadovnick AD, Eisen K, Ebers GC, Paty DW: Cause of death in patients attending multiple sclerosis clinics. Neurology 41(8), 1193-1196 (1991).
167. Fredrikson S, Cheng Q, Jiang GX, Wasserman D: Elevated suicide risk among patients with multiple sclerosis in Sweden. Neuroepidemiology 22(2), 146-152 (2003).
168. Bronnum-Hansen H, Stenager E, Nylev Stenager E, N Koch-Henriksen: Suicide among Danes with multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 76(10), 1457-1459 (2005).
169. Bronnum-Hansen H, Koch-Henriksen N, Stenager E: Trends in survival and cause of death in Danish patients with multiple sclerosis. Brain 127(Pt 4), 844-850 (2004).
170. Stenager EN, Stenager E, Koch-Henriksen N et al.: Suicide and multiple sclerosis: an epidemiological investigation. J. Neurol. Neurosurg. Psychiatry 55(7), 542-545 (1992).
171. Turner AP, Williams RM, Bowen JD, Kivlahan DR, Haselkorn JK: Suicidal ideation in multiple sclerosis. Arch. Phys. Med. Rehabil. 87(8), 1073-1078 (2006).
172. Stenager EN, Koch-Henriksen N, Stenager E: Risk factors for suicide in multiple sclerosis. Psychother. Psychosom. 65(2), 86-90 (1996).
173. Nielsen NM, Rostgaard K, Rasmussen S et al.: Cancer risk among patients with multiple sclerosis: a population-based register study. Int. J. Cancer 118(4), 979-984 (2006).
174. Lebrun C, Debouverie M, Vermersch P et al.: Cancer risk and impact of disease-modifying treatments in patients with multiple sclerosis. Mult. Scler. 14(3), 399-405 (2008).
175. Achiron A, Barak Y, Gail MA et al.: Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments. Breast Cancer Res. Treat. 89(3), 265-270 (2005).
176. Bahmanyar S, Montgomery SM, Hillert J, Ekbom A, Olsson T: Cancer risk among patients with multiple sclerosis and their parents. Neurology 72(13), 1170-1177 (2009).
177. Midgard R, Glattre E, Gronning M et al.: Multiple sclerosis and cancer in Norway. A retrospective cohort study. Acta Neurol. Scand. 93(6), 411-415 (1996).
178. Moller H, Kneller RW, Boice JD Jr, Olsen JH: Cancer incidence following hospitalization for multiple sclerosis in Denmark. Acta Neurol. Scand. 84(3), 214-220 (1991).
179. Wolinsky JS, Shochat T, Weiss S, Ladkani D: Glatiramer acetate treatment in PPMS: why males appear to respond favorably. J. Neurol. Sci. 286(1-2), 92-98 (2009).
180. Tomassini V, Paolillo A, Russo P et al.: Predictors of long-term clinical response to interferon b therapy in relapsing multiple sclerosis. J. Neurol. 253(3), 287-293 (2006).
181. Trojano M, Pellegrini F, Paolicelli D et al.: Post-marketing of disease modifying drugs in multiple sclerosis: an exploratory analysis of gender effect in interferon b treatment. J. Neurol. Sci. 286(1-2), 109-113 (2009).
182. Hutchinson M, Kappos L, Calabresi PA et al.: The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. J. Neurol. 256(3), 405-415 (2009).
183. SPECTRIMS study group: Randomized controlled trial of interferon- b-1a in secondary progressive MS: clinical results. Neurology 56(11), 1496-1504 (2001).
184. Neuteboom RF, Boon M, Catsman Berrevoets CE et al.: Prognostic factors after a first attack of inflammatory CNS demyelination in children. Neurology 71(13), 967-973 (2008).
185. Duquette P, Murray TJ, Pleines J et al.: Multiple sclerosis in childhood: clinical profile in 125 patients. J. Pediatr. 111(3), 359-363 (1987).
186. Ness JM, Chabas D, Sadovnick AD et al.: Clinical features of children and adolescents with multiple sclerosis. Neurology 68(16 Suppl. 2), S37-45 (2007).
187. Ghezzi A, Deplano V, Faroni J et al.: Multiple sclerosis in childhood: clinical features of 149 cases. Mult. Scler. 3(1), 43-46 (1997).
188. Stark W, Huppke P, Gartner J: Paediatric multiple sclerosis: the experience of the German Centre for Multiple Sclerosis in Childhood and Adolescence. J. Neurol. 255(Suppl. 6), 119-122 (2008).
189. Deryck O, Ketelaer P, Dubois B: Clinical characteristics and long term prognosis in early onset multiple sclerosis. J. Neurol. 253(6), 720-723 (2006).
190. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu M: Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol. 6(10), 887-902 (2007).
191. Tintore M, Arrambide G: Early onset multiple sclerosis: the role of gender. J. Neurol. Sci. 286(1-2), 31-34 (2009).
192. Achiron A and Gurevich M: Gender effects in relapsing-remitting multiple sclerosis: correlation between clinical variables and gene expression molecular pathways. J. Neurol. Sci. 286(1-2), 47-53 (2009).
193. Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D: Early onset multiple sclerosis: a longitudinal study. Neurology 59(7), 1006-1010 (2002).
194. Lucchinetti CF, Kiers L, ODuffy A et al.: Risk factors for developing multiple sclerosis after childhood optic neuritis. Neurology 49(5), 1413-1418 (1997).
195. Chirapapaisan N, Borchert MS: Pediatric optic neuritis. J. Med. Assoc. Thai. 91(3), 323-330 (2008).
196. Mikaeloff Y, Caridade G, Husson B, Suissa S, Tardieu M: Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse. Eur. J. Paediatr. Neurol. 11(2), 90-95 (2007).
197. Mikaeloff Y, Caridade G, Assi S, Suissa S, Tardieu M: Prognostic factors for early severity in a childhood multiple sclerosis cohort. Pediatrics 118(3), 1133-1139 (2006).
198. Runmarker B, Andersson C, Oden A, Andersen O: Prediction of outcome in multiple sclerosis based on multivariate models. J. Neurol. 241(10), 597-604 (1994).
199. Bergamaschi R: Prognostic factors in multiple sclerosis. Int. Rev. Neurobiol. 79, 423-447 (2007).
200. Zaffaroni M, Ghezzi A: The prognostic value of age, gender, pregnancy and endocrine factors in multiple sclerosis. Neurol. Sci. 21(4 Suppl. 2), S857-S860 (2000).
201. Runmarker B, Andersen O: Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 116(Pt 1), 117-134 (1993).
202. Phadke JG: Clinical aspects of multiple sclerosis in north-east Scotland with particular reference to its course and prognosis. Brain 113(Pt 6), 1597-1628 (1990).
203. Khaleeli Z, Ciccarelli O, Manfredonia F et al.: Predicting progression in primary progressive multiple sclerosis: a 10-year multicenter study. Ann. Neurol. 63(6), 790-793 (2008). (Pubitemid 351945538)
204. Koch M, Kingwell E, Rieckmann P, Tremlett H: The natural history of primary progressive multiple sclerosis. Neurology 73(23), 1996-2002 (2009).
205. Debouverie M, Louis S, Pittion-Vouyovitch S, Roederer T, Vespignani H: Multiple sclerosis with a progressive course from onset in Lorraine-Eastern France. J. Neurol. 254(10), 1370-1375 (2007).
206. Cottrell DA, Kremenchutzky M, Rice GP et al.: The natural history of multiple sclerosis: a geographically based study. 6. Applications to planning and interpretation of clinical therapeutic trials in primary progressive multiple sclerosis. Brain 122(Pt 4), 641-647 (1999). (Pubitemid 29158772)
207. Cottrell DA, Kremenchutzky M, Rice GP et al.: The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain 122 ( Pt 4), 625-639 (1999). (Pubitemid 29158771)
208. Beck RW, Trobe JD, Moke PS et al.: High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial. Arch. Ophthalmol. 121(7), 944-949 (2003).
209. Rizzo JF 3rd, Lessell S: Risk of developing multiple sclerosis after uncomplicated optic neuritis: a long-term prospective study. Neurology 38(2), 185-190 (1988).
210. Hely MA, McManis PG, Doran TJ, Walsh JC, McLeod JG: Acute optic neuritis: a prospective study of risk factors for multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 49(10), 1125-1130 (1986).
211. Kinnunen E: The incidence of optic neuritis and its prognosis for multiple sclerosis. Acta Neurol. Scand. 68(6), 371-377 (1983).
212. Isayama Y, Takahashi T, Shimoyoma T, Yamadori A: Acute optic neuritis and multiple sclerosis. Neurology 32(1), 73-76 (1982).
213. Swanton JK, Fernando KT, Dalton CM et al.: Early MRI in optic neuritis: the risk for clinically definite multiple sclerosis. Mult. Scler. 16(2), 156-165 (2010).
214. Sandberg-Wollheim M, Bynke H, Cronqvist S et al.: A long-term prospective study of optic neuritis: evaluation of risk factors. Ann. Neurol. 27(4), 386-393 (1990).
215. Rodriguez M, Siva A, Cross SA, OBrien PC, Kurland LT: Optic neuritis: a populationbased study in Olmsted County, Minnesota. Neurology 45(2), 244-250 (1995).
216. Fisniku LK, Brex PA, Altmann DR et al.: Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 131(Pt 3), 808-817 (2008).
217. Leray E, Morrissey SP, Yaouanq J et al.: Long-term survival of patients with multiple sclerosis in West France. Mult. Scler. 13(7), 865-874 (2007).
218. Midgard R, Albrektsen G, Riise T, Kvale G, Nyland H: Prognostic factors for survival in multiple sclerosis: a longitudinal, population based study in More and Romsdal, Norway. J. Neurol. Neurosurg. Psychiatry 58(4), 417-421 (1995).
219. Wallin MT, Page WF, Kurtzke JF: Epidemiology of multiple sclerosis in US veterans. VIII Long-term survival after onset of multiple sclerosis. Brain 123(Pt 8), 1677-1687 (2000).
220. Bronnum-Hansen H, Koch-Henriksen N, Hyllested K: Survival of patients with multiple sclerosis in Denmark: a nationwide, long-term epidemiologic survey. Neurology 44(10), 1901-1907 (1994).
221. Poser S, Poser W, Schlaf G et al.: Prognostic indicators in multiple sclerosis. Acta Neurol. Scand. 74(5), 387-392 (1986).
222. Sumelahti ML, Tienari PJ, Wikstrom J, Salminen TM, Hakama M: Survival of multiple sclerosis in Finland between 1964 and 1993. Mult. Scler. 8(4), 350-355 (2002).
223. Ragonese P, Aridon P, Mazzola MA et al.: Multiple sclerosis survival: a population-based study in Sicily. Eur. J. Neurol. (2009).
224. Riise T, Gronning M, Aarli JA et al.: Prognostic factors for life expectancy in multiple sclerosis analysed by Cox-models. J. Clin. Epidemiol. 41(10), 1031-1036 (1988).
225. Grytten Torkildsen N, Lie SA, Aarseth JH, Nyland H, Myhr KM: Survival and cause of death in multiple sclerosis: results from a 50-year follow-up in Western Norway. Mult. Scler. 14(9), 1191-1198 (2008).
226. Ramagopalan SV, Valdar W, Criscuoli M et al.: Age of puberty and the risk of multiple sclerosis: a population based study. Eur. J. Neurol. 16(3), 342-347 (2009).
227. Kurtzke JF, Hyllested K, Arbuckle JD et al.: Multiple sclerosis in the Faroe Islands. 7. Results of a case control questionnaire with multiple controls. Acta Neurol. Scand. 96(3), 149-157 (1997).
228. Operskalski EA, Visscher BR, Malmgren RM, Detels R: A case-control study of multiple sclerosis. Neurology 39(6), 825-829 (1989).
229. Sloka JS, Pryse-Phillips WE, Stefanelli M: The relation between menarche and the age of first symptoms in a multiple sclerosis cohort. Mult. Scler. 12(3), 333-339 (2006).
230. Zorgdrager A, De Keyser J: Premenstrual exacerbations of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 65(2), 279-280 (1998).
231. Zorgdrager A, De Keyser J: The premenstrual period and exacerbations in multiple sclerosis. Eur. Neurol. 48(4), 204-206 (2002).
232. De Las Heras V, De Andres C, Tellez N, Tintore M: Pregnancy in multiple sclerosis patients treated with immunomodulators prior to or during part of the pregnancy: a descriptive study in the Spanish population. Mult. Scler. 13(8), 981-984 (2007).
233. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T: Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N. Engl. J. Med. 339(5), 285-291 (1998).
234. Hellwig K, Brune N, Haghikia A et al.: Reproductive counselling, treatment and course of pregnancy in 73 German MS patients. Acta Neurol. Scand. 118(1), 24-28 (2008).
235. Salemi G, Callari G, Gammino M et al.: The relapse rate of multiple sclerosis changes during pregnancy: a cohort study. Acta Neurol. Scand. 110(1), 23-26 (2004).
236. Langer-Gould A, Huang SM, Gupta RA et al.: Exclusive breastfeeding and the risk of postpartum relapses in women with multiple sclerosis. Arch. Neurol. 66(8), 958-963 (2009).
237. Airas L, Saraste M, Rinta S et al.: Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells. Clin. Exp. Immunol. 151(2), 235-243 (2008).
238. Iorio R, Frisullo G, Nociti V et al.: T-bet, pSTAT1 and pSTAT3 expression in peripheral blood mononuclear cells during pregnancy correlates with post-partum activation of multiple sclerosis. Clin. Immunol. 131(1), 70-83 (2009).
239. Paavilainen T, Kurki T, Parkkola R et al.: Magnetic resonance imaging of the brain used to detect early post-partum activation of multiple sclerosis. Eur. J. Neurol. 14(11), 1216-1221 (2007).
240. Vukusic S, Hutchinson M, Hours M et al.: Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain 127(Pt 6), 1353-1360 (2004).
241. Gilmore W, Arias M, Stroud N et al.: Preliminary studies of cytokine secretion patterns associated with pregnancy in MS patients. J. Neurol. Sci. 224(1-2), 69-76 (2004).
242. Lopez C, Comabella M, Tintore M, Sastre-Garriga J, Montalban X: Variations in chemokine receptor and cytokine expression during pregnancy in multiple sclerosis patients. Mult. Scler. 12(4), 421-427 (2006).
243. Al-Shammri S, Rawoot P, Azizieh F et al.: Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis. J. Neurol. Sci. 222(1-2), 21-27 (2004).
244. Langer-Gould A, Gupta R, Huang S et al.: Interferon-g-producing T cells, pregnancy, and postpartum relapses of multiple sclerosis. Arch. Neurol. 67(1), 51-57 (2010).
245. Nakashima A, Ito M, Yoneda S et al.: Circulating and decidual Th17 cell levels in healthy pregnancy. Am. J. Reprod. Immunol. 63(2), 104-109 (2010).
246. Santner-Nanan B, Peek MJ, Khanam R et al.: Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J. Immunol. 183(11), 7023-7030 (2009).
247. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT: Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology 112(1), 38-43 (2004).
248. Sanchez-Ramon S, Navarro AJ, Aristimuno C et al.: Pregnancy-induced expansion of regulatory T-lymphocytes may mediate protection to multiple sclerosis activity. Immunol. Lett. 96(2), 195-201 (2005).
249. Neuteboom RF, Verbraak E, Voerman JS et al.: Serum leptin levels during pregnancy in multiple sclerosis. Mult. Scler. 15(8), 907-912 (2009).
250. Gilli F, Lindberg RL, Valentino P et al.: Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis. PLoS One 5(1), e8962 (2010).
251. Neuteboom RF, Verbraak E, Voerman JS et al.: First trimester interleukin 8 levels are associated with postpartum relapse in multiple sclerosis. Mult. Scler. 15(11), 1356-1358 (2009).
252. Vukusic S, Ionescu I, El-Etr M et al.: The Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) trial: rationale, objectives and state of advancement. J. Neurol. Sci. 286(1-2), 114-118 (2009).
253. Achiron A, Kishner I, Dolev M et al.: Effect of intravenous immunoglobulin treatment on pregnancy and postpartum-related relapses in multiple sclerosis. J. Neurol. 251(9), 1133-1137 (2004).
254. Haas J, Hommes OR: A dose comparison study of IVIG in postpartum relapsingremitting multiple sclerosis. Mult. Scler. 13(7), 900-908 (2007).
255. Hellwig K, Haghikia A, Agne H, Beste C, Gold R: Protective effect of breastfeeding in postpartum relapse rate of mothers with multiple sclerosis. Arch. Neurol. 66(12), 1580-1581; author reply 1581 (2009).
256. Gulick EE, Halper J: Influence of infant feeding method on postpartum relapse of mothers with MS. Int. J. MS Care 4(4), 4 (2002).
257. Nelson LM, Franklin GM, Jones MC: Risk of multiple sclerosis exacerbation during pregnancy and breast-feeding. JAMA 259(23), 3441-3443 (1988).
258. Iorio R, Nociti V, Frisullo G et al.: Breastfeeding and multiple sclerosis. Arch. Neurol. 66(12), 1580; author reply 1581 (2009).
259. Runmarker B, Andersen O: Pregnancy is associated with a lower risk of onset and a better prognosis in multiple sclerosis. Brain 118 (Pt 1), 253-261 (1995).
260. Verdru P, Theys P, DHooghe MB, Carton H: Pregnancy and multiple sclerosis: the influence on long term disability. Clin. Neurol. Neurosurg. 96(1), 38-41 (1994).
261. Lee M, OBrien: Pregnancy and multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 79(12), 1308-1311 (2008).
262. Koch M, Uyttenboogaart M, Heersema D, Steen C, De Keyser J: Parity and secondary progression in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 80(6), 676-678 (2009).
263. Sandberg-Wollheim M, Frank D, Goodwin TM et al.: Pregnancy outcomes during treatment with interferon b-1a in patients with multiple sclerosis. Neurology 65(6), 802-806 (2005).
264. Boskovic R, Wide R, Wolpin J, Bauer DJ, Koren G: The reproductive effects of b interferon therapy in pregnancy: a longitudinal cohort. Neurology 65(6), 807-811 (2005).
265. Weber-Schoendorfer C, Schaefer C: Multiple sclerosis, immunomodulators, and pregnancy outcome: a prospective observational study. Mult. Scler. 15(9), 1037-1042 (2009).
266. Dahl J, Myhr KM, Daltveit AK, Hoff JM, Gilhus NE: Pregnancy, delivery, and birth outcome in women with multiple sclerosis. Neurology 65(12), 1961-1963 (2005).
267. Mueller BA, Zhang J, Critchlow CW: Birth outcomes and need for hospitalization after delivery among women with multiple sclerosis. Am. J. Obstet. Gynecol. 186(3), 446-452 (2002).
268. Chen YH, Lin HL, Lin HC: Does multiple sclerosis increase risk of adverse pregnancy outcomes? A population-based study. Mult. Scler. 15(5), 606-612 (2009).
269. Patti F, Cavallaro T, Lo Fermo S et al.: Is in utero early-exposure to interferon b a risk factor for pregnancy outcomes in multiple sclerosis? J. Neurol. 255(8), 1250-1253 (2008).
270. Coyle PK, Johnson K, Pardo L, Stark Y: Pregnancy outcomes in patients with multiple sclerosis treated with glatiramer acetate (CopaxoneR) Neurology 60(5 Suppl. 1), A60 (2003).
271. Fernandez Liguori N, Klajn D, Acion L et al.: Epidemiological characteristics of pregnancy, delivery, and birth outcome in women with multiple sclerosis in Argentina (EMEMAR study). Mult. Scler. 15(5), 555-562 (2009).
272. Smith R, Studd JW: A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle. JR Soc. Med. 85(10), 612-613 (1992).
273. Holmqvist P, Wallberg M, Hammar M, Landtblom AM, Brynhildsen J: Symptoms of multiple sclerosis in women in relation to sex steroid exposure. Maturitas 54(2), 149-153 (2006).
274. Shabas D, Weinreb H: Preventive healthcare in women with multiple sclerosis. J. Womens Health Gend. Based Med. 9(4), 389-395 (2000).
275. Alonso A, Clark CJ: Oral contraceptives and the risk of multiple sclerosis: a review of the epidemiologic evidence. J. Neurol. Sci. 286(1-2), 73-75 (2009).
276. Wineman NM: Adaptation to multiple sclerosis: the role of social support, functional disability, and perceived uncertainty. Nurs. Res. 39(5), 294-299 (1990).
277. Harper AC, Harper DA, Chambers LW, Cino PM, Singer J: An epidemiological description of physical, social and psychological problems in multiple sclerosis. J. Chronic. Dis. 39(4), 305-310 (1986).
278. Stenager E, Stenager EN, Knudsen L, Jensen K: Multiple sclerosis: the impact on family and social life. Acta Psychiatr. Belg. 94(3), 165-174 (1994).
279. Gulick EE: Social support among persons with multiple sclerosis. Res. Nurs. Health 17(3), 195-206 (1994).
280. Good DM, Bower DA, Einsporn RL: Social support: gender differences in multiple sclerosis spousal caregivers. J. Neurosci. Nurs. 27(5), 305-311 (1995).
281. Steck B, Amsler F, Kappos L, Burgin D: Gender-specific differences in the process of coping in families with a parent affected by a chronic somatic disease (e.g. multiple sclerosis). Psychopathology 34(5), 236-244 (2001).
282. Gulick EE: Coping among spouses or significant others of persons with multiple sclerosis. Nurs. Res. 44(4), 220-225 (1995).
283. McCabe MP: Relationship functioning and sexuality among people with multiple sclerosis. J. Sex. Res. 39(4), 302-309 (2002).
284. Hammond SR, McLeod JG, Macaskill P, English DR: Multiple sclerosis in Australia: socioeconomic factors. J. Neurol. Neurosurg. Psychiatry 61(3), 311-313 (1996).
285. Glantz MJ, Chamberlain MC, Liu Q et al.: Gender disparity in the rate of partner abandonment in patients with serious medical illness. Cancer 115(22), 5237-5242 (2009).
286. Harrison T, Stuifbergen A, Adachi E, Becker H: Marriage, impairment, and acceptance in persons with multiple sclerosis. West J. Nurs. Res. 26(3), 266-285; discussion 286-292 (2004).
287. McCabe MP, McKern S, McDonald E, Vowels LM: Changes over time in sexual and relationship functioning of people with multiple sclerosis. J. Sex. Marital Ther. 29(4), 305-321 (2003).
288. Fletcher SG, Castro-Borrero W, Remington G et al.: Sexual dysfunction in patients with multiple sclerosis: a multidisciplinary approach to evaluation and management. Nat. Clin. Pract. Urol. 6(2), 96-107 (2009).
289. Waldron-Perrine B, Rapport LJ, Ryan KA, Harper KT: Predictors of life satisfaction among caregivers of individuals with multiple sclerosis. Clin. Neuropsychol. 23(3), 462-478 (2009).
290. Patti F, Amato MP, Battaglia MA et al.: Caregiver quality of life in multiple sclerosis: a multicentre Italian study. Mult. Scler. 13(3), 412-419 (2007).
291. Smith MM, Arnett PA: Factors related to employment status changes in individuals with multiple sclerosis. Mult. Scler. 11(5), 602-609 (2005).
292. Rodriguez M, Siva A, Ward J et al.: Impairment, disability, and handicap in multiple sclerosis: a population-based study in Olmsted County, Minnesota. Neurology 44(1), 28-33 (1994).
293. Larocca N, Kalb R, Scheinberg L, Kendall P: Factors associated with unemployment of patients with multiple sclerosis. J. Chronic. Dis. 38(2), 203-210 (1985).
294. Simmons RD, Tribe KL, McDonald EA: Living with multiple sclerosis: longitudinal changes in employment and the importance of symptom management. J. Neurol. 257(6), 926-936 (2010).
295. Rumrill PD Jr, Roessler RT, McMahon BT, Hennessey ML, Neath J: Gender as a differential indicator of the employment discrimination experiences of Americans with multiple sclerosis. Work 29(4), 303-311 (2007).
296. Hakim EA, Bakheit AM, Bryant TN et al.: The social impact of multiple sclerosis - a study of 305 patients and their relatives. Disabil. Rehabil. 22(6), 288-293 (2000).
297. Stolp-Smith KA, Atkinson EJ, Campion ME, OBrien PC, Rodriguez M: Health care utilization in multiple sclerosis: a population-based study in Olmsted County, MN. Neurology 50(6), 1594-1600 (1998).
298. Berg J, Lindgren P, Fredrikson S, Kobelt G:Costs and quality of life of multiple sclerosis in Sweden. Eur. J. Health Econ. 7(Suppl. 2), S75-85 (2006).
299. Krokavcova M, van Dijk JP, Nagyova I et al.: Perceived health status as measured by the SF-36 in patients with multiple sclerosis: a review. Scand. J. Caring Sci. (2009) (Epub ahead of print).
300. Pugliatti M, Riise T, Nortvedt MW et al.: Self-perceived physical functioning and health status among fully ambulatory multiple sclerosis patients. J. Neurol. 255(2), 157-162 (2008).
301. Idiman E, Uzunel F, Ozakbas S et al.: Cross-cultural adaptation and validation of multiple sclerosis quality of life questionnaire (MSQOL-54) in a Turkish multiple sclerosis sample. J. Neurol. Sci. 240(1-2), 77-80 (2006).
302. Solari A, Filippini G, Mendozzi L et al.: Validation of Italian multiple sclerosis Quality of Life 54 Questionnaire. J. Neurol. Neurosurg. Psychiatry 67(2), 158-162 (1999).
303. Kobelt G, Berg J, Lindgren P et al.: Costs and quality of life in multiple sclerosis in The Netherlands. Eur. J. Health Econ. 7(Suppl. 2), S55-64 (2006).
304. Kobelt G, Berg J, Lindgren P et al.: Costs and quality of life of multiple sclerosis in Germany. Eur. J. Health Econ. 7(Suppl. 2), S34-44 (2006).
305. Kobelt G, Berg J, Lindgren P, Gerfin A, Lutz J: Costs and quality of life of multiple sclerosis in Switzerland. Eur. J. Health Econ. 7(Suppl. 2), S86-95 (2006).
306. Kobelt G, Berg J, Lindgren P et al.: Costs and quality of life of multiple sclerosis in the United Kingdom. Eur. J. Health Econ. 7(Suppl. 2), S96-104 (2006).
307. Kobelt G, Berg J, Atherly D, Hadjimichael O: Costs and quality of life in multiple sclerosis: a cross-sectional study in the United States. Neurology 66(11), 1696-1702 (2006). (Pubitemid 43964625)
308. Fraser C, Polito S: A comparative study of self-efficacy in men and women with multiple sclerosis. J. Neurosci. Nurs. 39(2), 102-106 (2007).
309. Casetta I, Riise T, Wamme Nortvedt M et al.: Gender differences in health-related quality of life in multiple sclerosis. Mult. Scler. 15(11), 1339-1346 (2009).
310. Ksobelt G, Berg J, Lindgren P et al.: Costs and quality of life of multiple sclerosis in Italy. Eur. J. Health Econ. 7(Suppl. 2), S45-S54 (2006).
311. Miller A, Dishon S: Health-related quality of life in multiple sclerosis: the impact of disability, gender and employment status. Qual. Life Res. 15(2), 259-271 (2006).
312. Pfaffenberger N, Pfeiffer KP, Deibl M et al.: Association of factors influencing healthrelated quality of life in MS. Acta Neurol. Scand. 114(2), 102-108 (2006).
313. Pfennings L, Cohen L, Ader H et al.: Exploring differences between subgroups of multiple sclerosis patients in health-related quality of life. J. Neurol. 246(7), 587-591 (1999). (Pubitemid 29376285)
314. Fischer S, Huber CA, Imhof L et al.: Suicide assisted by two Swiss right-to-die organisations. J. Med. Ethics 34(11), 810-814 (2008).