We aimed to examine the incidence and disease course of late-onset multiple sclerosis (LOMS) compared with adult-onset MS (AOMS) in our clinic cohort, stratified based on gender and race, since both have been reported as important modifiers of disease outcomes in MS.
Methods:
Patients with LOMS and AOMS were compared in terms of demographic characteristics and disease course characteristics. Combined effects were investigated with a logistic regression model. Time from disease onset to sustained Expanded Disability Status Scale (EDSS) score of 6 was investigated using an extension of log-rank test appropriate for interval-censored data.
Results:
Some 7.96% of 4273 patients studied had an onset of MS after the age of 50 years (LOMS), and 1.33% experienced an onset after age 60. Progressive onset was more common in LOMS relative to AOMS. The proportion of women with progressive-onset disease was similar in AOMS and LOMS. Time to EDSS 6 was delayed in AOMS females compared with males; however, it was similar between males and females in the LOMS group.
Conclusions:
Women with LOMS have a different trajectory in terms of disease progression than women with AOMS. The effect of menopause combined with race/ethnicity on the MS disease course requires further investigation.
RosatiG. The prevalence of multiple sclerosis in the world: an update. Neurol Sci2001; 22: 117–139.
2.
PugliattiMRosatiGCartonH. The epidemiology of multiple sclerosis in Europe. Eur J Neurol2006; 13: 700-722.
3.
OrtonSMHerreraBMYeeIM. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol2006; 5: 932–936.
4.
RamagopalanSVValdarWCriscuoliM. Age of puberty and the risk of multiple sclerosis: a population based study. Eur J Neurol2009; 16: 342–347.
5.
VukusicSConfavreuxC. Pregnancy and multiple sclerosis: the children of PRIMS. Clin Neurol Neurosurg2006; 108: 266–270.
6.
GoldSMVoskuhlRR. Estrogen and testosterone therapies in multiple sclerosis. Prog Brain Res2009; 175: 239–251.
7.
PapenfussTLPowellNDMcClainMA. Estriol generates tolerogenic dendritic cells in vivo that protect against autoimmunity. J Immunol2011; 186: 3346–3355.
8.
VoskuhlRRPalaszynskiK. Sex hormones in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. Neuroscientist2001; 7: 258–270.
9.
NicotA. Gender and sex hormones in multiple sclerosis pathology and therapy. Front Biosci2009; 14: 4477–4515.
10.
MowryEMPesicMGrimesBDeenSRBacchettiPWaubantE. Clinical predictors of early second event in patients with clinically isolated syndrome. J Neurol2009; 256: 1061–1066.
11.
RamagopalanSVYeeIMDymentDA. Parent-of-origin effect in multiple sclerosis: observations from interracial matings. Neurology2009; 73: 602–605.
12.
ChitnisTGlanzBJaffinSHealyB. Demographics of pediatric-onset multiple sclerosis in an MS center population from the Northeastern United States. Mult Scler2009; 15: 627–631.
13.
GhezziADeplanoVFaroniJ. Multiple sclerosis in childhood: clinical features of 149 cases. Mult Scler1997; 3: 43–46.
14.
RuggieriMIannettiPPolizziAPavoneLGrimaldiLM. Multiple sclerosis in children under 10 years of age. Neurol Sci2004; 25Suppl 4: S326-S335.
PhadkeJG. Clinical aspects of multiple sclerosis in north-east Scotland with particular reference to its course and prognosis. Brain1990; 113 (Pt 6): 1597–1628.
PolliackMLBarakYAchironA. Late-onset multiple sclerosis. J Am Geriatr Soc2001; 49: 168–171.
19.
TremlettHDevonshireV. Is late-onset multiple sclerosis associated with a worse outcome?Neurology2006; 67: 954–959.
20.
NoseworthyJPatyDWonnacottTFeasbyTEbersG. Multiple sclerosis after age 50. Neurology1983; 33: 1537–1544.
21.
AzzimondiGStracciariARinaldiRD’AlessandroRPazzagliaP. Multiple sclerosis with very late onset: report of six cases and review of the literature. Eur Neurol1994; 34: 332–336.
22.
HoogeJPRedekopWK. Multiple sclerosis with very late onset. Neurology1992; 42: 1907–1910.
23.
WhiteADSwinglerRJCompstonDA. Features of multiple sclerosis in older patients in South Wales. Gerontology1990; 36: 159–164.
24.
Lyon-CaenOIzquierdoGMarteauRLhermitteFCastaignePHauwJJ. Late onset multiple sclerosis. A clinical study of 16 pathologically proven cases. Acta Neurol Scand1985; 72: 56–60.
25.
RunmarkerBAnderssonCOdenAAndersenO. Prediction of outcome in multiple sclerosis based on multivariate models. J Neurol1994; 241: 597–604.
26.
StankoffBMrejenSTourbahA. Age at onset determines the occurrence of the progressive phase of multiple sclerosis. Neurology2007; 68: 779–781.
27.
KantarciOSivaAEraksoyM. Survival and predictors of disability in Turkish MS patients. Turkish Multiple Sclerosis Study Group (TUMSSG). Neurology1998; 51: 765–772.
28.
TortorellaCBellacosaAPaolicelliD. Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis. J Neurol Sci2005; 239: 95–99.
29.
de SezeJDelalandeSMichelinE. Brain MRI in late-onset multiple sclerosis. Eur J Neurol2005; 12: 241–244.
30.
HealyBCEnglerDGholipourTWeinerHBakshiRChitnisT. Accounting for disease-modifying therapy in models of clinical progression in multiple sclerosis. J Neurol Sci2011.
31.
GholipourTHealyBBaruchNFWeinerHLChitnisT. Demographic and clinical characteristics of malignant multiple sclerosis. Neurology2011; 76: 1996–2001.
32.
PolmanCHReingoldSCEdanG. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol2005; 58: 840–846.
33.
DeanGKurtzkeJF. A critical age for the acquisition of multiple sclerosis. Trans Am Neurol Assoc1970; 95: 232–233.
34.
KisBRumbergBBerlitP. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol2008; 255: 697–702.
35.
LublinFDReingoldSC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology1996; 46: 907–911.
36.
KurtzkeJ. Rating neurologic impairment in multiple sclerosis: An Expanded Disability Status Scale (EDSS). Neurology1983; 33: 1444–1452.
37.
FinkelsteinDM. A proportional hazards model for interval-censored failure time data. Biometrics1986; 42: 845–854.
38.
MartinelliVRodegherMMoiolaLComiG. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci2004; 25Suppl 4: S350–355.
39.
SimFJZhaoCPenderisJFranklinRJ. The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci2002; 22: 2451–2459.
40.
LuTPanYKaoSY. Gene regulation and DNA damage in the ageing human brain. Nature2004; 429: 883–891.
41.
FilippiMWolinskyJSSormaniMPComiG. Enhancement frequency decreases with increasing age in relapsing-remitting multiple sclerosis. Neurology2001; 56: 422–423.
RamagopalanSVByrnesJKOrtonSM. Sex ratio of multiple sclerosis and clinical phenotype. Eur J Neurol2010; 17: 634–637.
44.
KatoITonioloPAkhmedkhanovAKoenigKLShoreRZeleniuch-JacquotteA. Prospective study of factors influencing the onset of natural menopause. J Clin Epidemiol1998; 51: 1271–1276.
45.
WundesAAmtmannDBrownTChristianS. Menopause in women with multiple sclerosis. International Journal of MS Care2011; 13: 47.
46.
MarrieRACutterGTyryTVollmerTCampagnoloD. Does multiple sclerosis-associated disability differ between races?Neurology2006; 66: 1235–1240.
47.
CreeBAReichDEKhanO. Modification of multiple sclerosis phenotypes by African ancestry at HLA. Arch Neurol2009; 66: 226–233.
48.
ZuvichRLMcCauleyJLPericak-VanceMAHainesJL. Genetics and pathogenesis of multiple sclerosis. Semin Immunol2009; 21: 328–333.
49.
BenedictRHZivadinovR. Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol2011; 7: 332–342.
50.
GreerJMMcCombePA. Role of gender in multiple sclerosis: clinical effects and potential molecular mechanisms. J Neuroimmunol2011; 234: 7–18.
51.
SawcerSHellenthalGPirinenM. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature2011; 476: 214–219.
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