Skip to main content

Advertisement

SpringerLink
Log in

Multiple Sclerosis in the Elderly Patient

  • Review Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Multiple sclerosis (MS) is an acquired inflammatory demyelinating disease of the CNS that is typically diagnosed in the second or third decade of life. It is generally believed that over the last few decades the life expectancy of patients with adult onset MS (AOMS) has approached that of the general population as a result of better medical and nursing care. Thus, an increasing number of MS patients are entering or have reached senescence. A second group of elderly patients with MS that may be very different in terms of disease pathogenesis are patients with late onset MS (LOMS). The diagnosis in LOMS patients can be challenging because of a large number of age-associated MS differential diagnoses, atypical presentations, a low index of suspicion and the lack of diagnostic criteria specific to this age group. Also, specific problems these patients encounter have only recently become a focus of attention. Changes in renal and hepatic function with age, in addition to the coexistence of medical co-morbidities, require special attention in the management of elderly patients with MS. In this review we outline the characteristics of senescent AOMS and LOMS patients. In addition, we discuss therapeutic strategies in elderly patients with MS based on our knowledge of immunosenescence and age-associated characteristics of this disorder. Given the overall aging of the population, focusing on these two patient groups appears highly relevant.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol 1992; 10: 153–87

    Article  PubMed  CAS  Google Scholar 

  2. Steinman L. Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system. Cell 1996; 85(3): 299–302

    Article  PubMed  CAS  Google Scholar 

  3. Stüve O, Zamvil SS. Neurologic diseases. In: Parslow TG, Stites DP, Terr AI, et al., editors. Medical immunology. San Francisco (CA): McGraw Hill, 2001: 510–26

    Google Scholar 

  4. Anderson DW, Ellenberg JH, Leventhal CM, et al. Revised estimate of the prevalence of multiple sclerosis in the United States. Ann Neurol 1992; 31(3): 333–6

    Article  PubMed  CAS  Google Scholar 

  5. Poser CM. The epidemiology of multiple sclerosis: a general overview. Ann Neurol 1994 Dec; 36Suppl. 2: S180–93

    Article  PubMed  Google Scholar 

  6. Hanefeld F, Bauer HJ, Christen HJ, et al. Multiple sclerosis in childhood: report of 15 cases. Brain Dev 1991; 13(6): 410–6

    Article  PubMed  CAS  Google Scholar 

  7. Duquette P, Murray TJ, Pleines J, et al. Multiple sclerosis in childhood: clinical profile in 125 patients. J Pediatr 1987; 111(3): 359–63

    Article  PubMed  CAS  Google Scholar 

  8. Poser S, Raun NE, Poser W. Age at onset, initial symptomatology and the course of multiple sclerosis. Acta Neurol Scand 1982; 66(3): 355–62

    Article  PubMed  CAS  Google Scholar 

  9. Kurtzke JF, Page WF, Murphy FM, et al. Epidemiology of multiple sclerosis in US veterans: 4, age at onset. Neuroepidemiology 1992; 11(4-6): 226–35

    Article  PubMed  CAS  Google Scholar 

  10. Liguori M, Marrosu MG, Pugliatti M, et al. Age at onset in multiple sclerosis. Neurol Sci 2000; 21: S825–9

    Article  PubMed  CAS  Google Scholar 

  11. Manzi S. Epidemiology of systemic lupus erythematosus. Am J Manag Care 2001; 7: S474–9

    PubMed  CAS  Google Scholar 

  12. Alarcon GS. Epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am 1995; 21: 589–604

    PubMed  CAS  Google Scholar 

  13. Fox RI. Epidemiology, pathogenesis, animal models, and treatment of Sjogren’s syndrome. Curr Opin Rheumatol 1994; 6: 501–8

    Article  PubMed  CAS  Google Scholar 

  14. Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study: predictive value of the early clinical course. Brain 1989; 112: 1419–28

    Article  PubMed  Google Scholar 

  15. Thompson AJ, Kermode AG, Wicks D, et al. Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 1991; 29: 53–62

    Article  PubMed  CAS  Google Scholar 

  16. Thompson AJ, Montalban X, Barkhof F, et al. Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 2000; 47: 831–5

    Article  PubMed  CAS  Google Scholar 

  17. Vukusic S, Confavreux C. Primary and secondary progressive multiple sclerosis. J Neurol Sci 2003; 206: 153–5

    Article  PubMed  Google Scholar 

  18. Thompson AJ, Polman CH, Miller DH, et al. Primary progressive multiple sclerosis. Brain 1997; 120: 1085–96

    Article  PubMed  Google Scholar 

  19. Confavreux C, Aimard G, Devic M. Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain 1980; 103: 281–300

    Article  PubMed  CAS  Google Scholar 

  20. Riise T, Grønning M, Fernández O, et al. Early prognostic factors for disability in multiple sclerosis: a European multicenter study. Acta Neurol Scand 1992; 85: 212–8

    Article  PubMed  CAS  Google Scholar 

  21. Trojano M, Avolio C, Manzari C, et al. Multivariate analysis of predictive factors of multiple sclerosis course with a validated method to assess clinical events. J Neurol Neurosurg Psychiatry 1995; 58: 300–6

    Article  PubMed  CAS  Google Scholar 

  22. Lublin FD, Reingold SC. 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. Neurology 1996; 46: 907–11

    Article  PubMed  CAS  Google Scholar 

  23. Minden SL, Frankel D, Hadden LS, et al. Disability in elderly people with multiple sclerosis: an analysis of baseline data from the Sonya Slifka Longitudinal Multiple Sclerosis Study. NeuroRehabilitation 2004; 19: 55–67

    PubMed  Google Scholar 

  24. Baum HM, Rothschild BB. The incidence and prevalence of multiple sclerosis. Ann Neurol 1981; 10: 420–8

    Article  PubMed  CAS  Google Scholar 

  25. Kranz JMS, Kurland LT, Schuman LM, et al. Multiple sclerosis in Olmsted and Mower Counties, Minnesota. Neuroepidemiology 1983; 2: 206–18

    Article  Google Scholar 

  26. Kurtzke JF, Beebe GW, Norman Jr EJ. Epidemiology of multiple sclerosis in US veterans: I, race, sex, and geographic distribution. Neurology 1979; 29: 1228–35

    Article  PubMed  CAS  Google Scholar 

  27. Minden SL, Marder WD. Multiple sclerosis: a statistical portrait: a compendium of data on demographics, disability and health services utilization in the United States: report to the National Multiple Sclerosis Society. Cambridge (MA): Abt Associates Inc., 1993

    Google Scholar 

  28. Nelson LM, Hamman RF, Thompson DS, et al. Higher than expected prevalence of multiple sclerosis in northern Colorado: dependence on methodologic issues. Neuroepidemiology 1986; 5: 17–28

    Article  PubMed  CAS  Google Scholar 

  29. Wynn DR, Rodriguez M, O’Fallon WM, et al. A reappraisal of the epidemiology of multiple sclerosis in Olmsted County, Minnesota. Neurology 1990; 40: 780–6

    Article  PubMed  CAS  Google Scholar 

  30. Finlayson M. Health and social profile of older adults with MS: findings from three studies. Int J MS Care 2002; 4: 139–51

    Google Scholar 

  31. Klewer J, Pohlau D, Nippert I, et al. Problems reported by elderly patients with multiple sclerosis. J Neurosci Nurs 2001; 33: 167–71

    Article  PubMed  CAS  Google Scholar 

  32. Polliack ML, Barak Y, Achiron A. Late onset multiple sclerosis. J Am Geriatr Soc 2001; 49: 168–71

    Article  PubMed  CAS  Google Scholar 

  33. Bauer HJ, Hanefled F. Multiple sclerosis: its impact from childhood to old age. London: W.B. Saunders, 1993

    Google Scholar 

  34. Phadke JG. Clinical aspects of multiple sclerosis in northeast Scotland with particular reference to its course and prognosis. Brain 1990; 113: 1597–628

    Article  PubMed  Google Scholar 

  35. White AD, Swingler RJ, Compston DA. Features of multiple sclerosis in older patients in South Wales. Gerontology 1990; 36:159–64

    Article  PubMed  CAS  Google Scholar 

  36. Pittock SJ, Mayr WT, McClelland RL, et al. Change in MS-related disability in a population-based cohort: a 10-year follow up study. Neurology 2004; 62: 51–9

    Article  PubMed  CAS  Google Scholar 

  37. Confavreux C, Vukusic S, Moreau T, et al. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000; 343: 1430–8

    Article  PubMed  CAS  Google Scholar 

  38. Kantarci O, Siva A, Eraksoy M, et al., Turkish Multiple Sclerosis Study Group (TUMSSG). Survival and predictors of disability in Turkish MS patients. Neurology 1998; 51: 765–72

    Article  PubMed  CAS  Google Scholar 

  39. Bergamaschi R, Berzuini C, Romani A, et al. Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis. J Neurol Sci 2001; 189: 13–21

    Article  PubMed  CAS  Google Scholar 

  40. Amato MP, Ponziani G, Bartolozzi ML, et al. A prospective study on the natural history of multiple sclerosis: clues to the conduct and interpretation of clinical trials. J Neurol Sci 1999; 168: 96–106

    Article  PubMed  CAS  Google Scholar 

  41. Patty D, Boilo A, Vorobeichik G. Multiple sclerosis with early and late disease onset. In: McDonald WI, Nose-worthy J, editors. Multiple sclerosis 2. Boston (MA): Butterworth Heinemann, 2003: 285–302

    Chapter  Google Scholar 

  42. Noseworthy J, Paty D, Wonnacott T, et al. Multiple sclerosis after age of 50. Neurology 1983; 33: 1537–44

    Article  PubMed  CAS  Google Scholar 

  43. Cazzullo CL, Ghezzi A, Marforio S, et al. Clinical picture of multiple sclerosis with late onset. Acta Neurol Scand 1978; 58: 190–6

    Article  PubMed  CAS  Google Scholar 

  44. Compston A, Cole AJ. Multiple sclerosis. Lancet 2002; 359: 1221–31

    Article  PubMed  Google Scholar 

  45. Tremlett H, Paty D, Devonshire V. Disability progression in multiple sclerosis is slower than previously reported. Neurology 2006; 66: 172–7

    Article  PubMed  Google Scholar 

  46. Simone IL, Carrara D, Tortorella C, et al. Course and prognosis in early-onset MS: comparison with adult-onset forms. Neurology 2002 Dec 24; 59(12): 1922–8

    Article  PubMed  CAS  Google Scholar 

  47. Tremlett H, Devonshire V. Is late onset multiple sclerosis associated with a worse outcome? Neurology 2006; 67: 954–9

    Article  PubMed  Google Scholar 

  48. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–52

    Article  PubMed  CAS  Google Scholar 

  49. Wolfson C, Wolfson DB. The latent period of multiple sclerosis: a critical review. Epidemiology 1993; 4: 464–70

    Article  PubMed  CAS  Google Scholar 

  50. Lu T, Pan Y, Kao SY, et al. Gene regulation and DNA damage in the ageing human brain. Nature 2004; 429: 883–91

    Article  PubMed  CAS  Google Scholar 

  51. Sim FJ, Zhao C, Penderis J, et al. The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci 2002; 22: 2451–9

    PubMed  CAS  Google Scholar 

  52. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol 2008; 255: 697–702

    Article  PubMed  Google Scholar 

  53. Okuda DT, Mowry EM, Beheshtian A, et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radio-logically isolated syndrome. Neurology 2009; 72: 800–5

    Article  PubMed  CAS  Google Scholar 

  54. Hooge JP, Redekop WK. Multiple sclerosis with very late onset. Neurology 1992; 42: 1907–10

    Article  PubMed  CAS  Google Scholar 

  55. Gomez-Garcia AO, Fernandez-Concepcion O, Milan-Ginjauma E. Clinical-epidemiological characteristics of late onset multiple sclerosis. Rev Neurol 1997; 25: 1863–6

    PubMed  CAS  Google Scholar 

  56. Moreira MA, Felipe E, Mendes MF, et al. Multiple sclerosis: descriptive study of its clinical forms in 302 cases. Arq Neuropsiquiatr 2000; 58: 460–6

    Article  PubMed  CAS  Google Scholar 

  57. Hawkins SA, McDonnel GV. Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J Neurol Neurosurg Psychiatry 1999; 67: 148–52

    Article  PubMed  CAS  Google Scholar 

  58. Herndon RM. Multiple sclerosis mimics. Adv Neurol 2006; 98: 161–6

    PubMed  Google Scholar 

  59. Spielman RS, McGinnis RE, Ewens WJ. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993; 52: 506–16

    PubMed  CAS  Google Scholar 

  60. Sawcer S, Jones HB, Feakes R, et al. A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22. Nat Genet 1996; 13: 464–8

    Article  PubMed  CAS  Google Scholar 

  61. Kuokkanen S, Sundvall M, Terwilliger JD, et al. A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2. Nat Genet 1996; 13:477–80

    Article  PubMed  CAS  Google Scholar 

  62. Ebers GC, Kukay K, Bulman DE, et al. A full genome search in multiple sclerosis. Nat Genet 1996; 13: 472–6

    Article  PubMed  CAS  Google Scholar 

  63. Haines JL, Ter-Minassian M, Bazyk A, et al. A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex: the Multiple Sclerosis Genetics Group. Nat Genet 1996; 13: 469–71

    Article  PubMed  CAS  Google Scholar 

  64. Barcellos LF, Oksenberg JR, Begovich AB, et al., Multiple Sclerosis Genetics Group. HLA-DR2 Dose effect on susceptibility to multiple sclerosis and influence on disease course. Am J Hum Genet 2003; 72: 710–6

    Article  PubMed  CAS  Google Scholar 

  65. Villoslada P, Barcellos LF, Rio J, et al. The HLA locus and multiple sclerosis in Spain: role in disease susceptibility, clinical course and response to interferon-beta. J Neuroimmunol 2002; 130: 194–201

    Article  PubMed  CAS  Google Scholar 

  66. Mazurek AA, Shi J. APOE epsilon4 allele is associated with cognitive impairment in patients with multiple sclerosis [letter]. Neurology 2008; 71: 1203

    Article  PubMed  Google Scholar 

  67. Shi J, Zhao CB, Vollmer TL, et al. APOE epsilon 4 allele is associated with cognitive impairment in patients with multiple sclerosis. Neurology 2008; 70: 185–90

    Article  PubMed  CAS  Google Scholar 

  68. Pinholt M, Frederiksen JL, Andersen PS, et al. Apo E in multiple sclerosis and optic neuritis: the apo E-epsilon4 allele is associated with progression of multiple sclerosis. Mult Scler 2005; 11: 511–5

    Article  PubMed  CAS  Google Scholar 

  69. Enzinger C, Ropele S, Smith S, et al. Accelerated evolution of brain atrophy and “black holes” in MS patients with APOE-epsilon 4. Ann Neurol 2004; 55: 563–9

    Article  PubMed  CAS  Google Scholar 

  70. Becker KG. APOE genotype is a major predictor of long-term progression of disability in MS. Neurology 2001; 57: 2148–9

    Article  PubMed  CAS  Google Scholar 

  71. Fazekas F, Strasser-Fuchs S, Kollegger H, et al. Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis. Neurology 2001; 57: 853–7

    Article  PubMed  CAS  Google Scholar 

  72. Orlando L. AD gene accelerates MS. Trends Neurosci 2001; 24: 257

    Google Scholar 

  73. Chapman J, Vinokurov S, Achiron A, et al. APOE genotype is a major predictor of long-term progression of disability in MS. Neurology 2001; 56: 312–6

    Article  PubMed  CAS  Google Scholar 

  74. Portaccio E, Goretti B, Zipoli V, et al. APOE-{varepsilon}4 is not associated with cognitive impairment in relapsing-remitting multiple sclerosis. Mult Scler 2009; 15(12): 1489–94

    Article  PubMed  Google Scholar 

  75. van der Walt A, Stankovich J, Bahlo M, et al. Apolipoprotein genotype does not influence MS severity, cognition, or brain atrophy. Neurology 2009; 73: 1018–25

    Article  PubMed  CAS  Google Scholar 

  76. Guerrero AL, Laherrán E, Gutiérrez F, et al. Apolipoprotein E genotype does not associate with disease severity measured by Multiple Sclerosis Severity Score. Acta Neurol Scand 2008; 117: 21–5

    PubMed  CAS  Google Scholar 

  77. Ramagopalan SV, Deluca GC, Morrison KM, et al. No effect of APOE and PVRL2 on the clinical outcome of multiple sclerosis. J Neuroimmunol 2007 May; 186:156–60

    Article  PubMed  CAS  Google Scholar 

  78. Koutsis G, Panas M, Karadima G, et al. APOE genotypes in Greek multiple sclerosis patients: no effect on the MS Severity Score. J Neurol 2007; 254: 394–5

    Article  PubMed  Google Scholar 

  79. Sedano MI, Calmarza P, Perez L, et al. No association of apolipoprotein E epsilon4 genotype with faster progression or less recovery of relapses in a Spanish cohort of multiple sclerosis. Mult Scler 2006; 12: 13–8

    Article  PubMed  CAS  Google Scholar 

  80. Zwemmer JN, van Veen T, van Winsen L, et al. No major association of ApoE genotype with disease characteristics and MRI findings in multiple sclerosis. Mult Scler 2004; 10: 272–7

    Article  PubMed  CAS  Google Scholar 

  81. Weatherby SJ, Mann CL, Fryer AA, et al. No association between the APOE epsilon4 allele and outcome and susceptibility in primary progressive multiple sclerosis [letter]. J Neurol Neurosurg Psychiatry 2000; 68: 532

    Article  Google Scholar 

  82. Savettieri G, Andreoli V, Bonavita S, et al. Apolipoprotein E genotype does not influence the progression of multiple sclerosis. J Neurol 2003; 250: 1094–8

    Article  PubMed  CAS  Google Scholar 

  83. Stüve O, Korth C, Gabatto P, et al. Genetic polymorphism at codon 129 of the prion protein gene is not associated with multiple sclerosis. Arch Neurol 2009; 66: 280–1

    Article  PubMed  Google Scholar 

  84. Vandenbroeck K, Martino G, Marrosu M, et al. Occurrence and clinical relevance of an interleukin-4 gene polymorphism in patients with multiple sclerosis. J Neuroimmunol 1997; 76: 189–92

    Article  PubMed  Google Scholar 

  85. Linton P, Thoman ML. T cell senescence. Front Biosci 2001; 6: D248–61

    Article  PubMed  CAS  Google Scholar 

  86. Fransson C, Mooney J, Kinane DF, et al. Differences in the inflammatory response in young and old human subjects during the course of experimental gingivitis. J Clin Periodontol 1999; 26: 453–60

    Article  PubMed  CAS  Google Scholar 

  87. Niwa Y, Kasama T, Miyachi Y, et al. Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: cross-sectional and longitudinal studies. Life Sci 1989; 44: 1655–64

    Article  PubMed  CAS  Google Scholar 

  88. Fulop T, Foris G, Leovey A. Age-related changes in cAMP and cGMP levels during phagocytosis in human polymorphonuclear leukocytes. Mech Ageing Dev 1984; 27:233–7

    Article  PubMed  CAS  Google Scholar 

  89. Biasi D, Carletto A, Dell’Agnola C, et al. Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects. Inflammation 1996; 20: 673–81

    Article  PubMed  CAS  Google Scholar 

  90. Damtew B, Spagnuolo PJ, Goldsmith GG, et al. Neutrophil adhesion in the elderly: inhibitory effects of plasma from elderly patients. Clin Immunol Immunopathol 1990; 54: 247–55

    Article  PubMed  CAS  Google Scholar 

  91. Tortorella C, Piazzolla G, Spaccavento F, et al. Age-related effects of oxidative metabolism and cyclic AMP signaling on neutrophil apoptosis. Mech Ageing Dev 1999; 110: 195–205

    Article  PubMed  CAS  Google Scholar 

  92. Tortorella C, Piazzolla G, Spaccavento F, et al. Spontaneous and Fas-induced apoptotic cell death in aged neutrophils. J Clin Immunol 1998; 18: 321–9

    Article  PubMed  CAS  Google Scholar 

  93. Fülöp Jr T, Fouquet C, Allaire P, et al. Changes in apoptosis of human polymorphonuclear granulocytes with aging. Mech Ageing Dev 1997; 96: 15–34

    Article  PubMed  Google Scholar 

  94. Steger MM, Maczek C, Grubeck-Loebenstein B. Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals. Clin Exp Immunol 1996; 105: 544–50

    Article  PubMed  CAS  Google Scholar 

  95. Lung TL, Saurwein-Teissl M, Parson W, et al. Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. Vaccine 2000; 18: 1606–12

    Article  PubMed  CAS  Google Scholar 

  96. Pietschmann P, Hahn P, Kudlacek S, et al. Surface markers and transendothelial migration of dendritic cells from elderly subjects. Exp Gerontol 2000; 35: 213–24

    Article  PubMed  CAS  Google Scholar 

  97. Komatsubara S, Cinader B, Muramatsu S. Polymorphism of age-related changes in stimulatory capacity of murine dendritic cells. Mech Ageing Dev 1986; 37: 163–73

    Article  PubMed  CAS  Google Scholar 

  98. Renshaw M, Rockwell J, Engleman C, et al. Cutting edge: impaired Toll-like receptor expression and function in aging. J Immunol 2002; 169: 4697–701

    PubMed  CAS  Google Scholar 

  99. Karpus WJ, Kennedy KJ. MIP-1alpha and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as Th1/Th2 lymphocyte differentiation. J Leukoc Biol 1997; 62: 681–7

    PubMed  CAS  Google Scholar 

  100. McManus C, Berman JW, Brett FM, et al. MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ hybridization study. J Neuroimmunol 1998; 86: 20–9

    Article  PubMed  CAS  Google Scholar 

  101. Swift ME, Burns AL, Gray KL, et al. Age-related alterations in the inflammatory response to dermal injury. J Invest Dermatol 2001; 117: 1027–35

    Article  PubMed  CAS  Google Scholar 

  102. Makinodan T. Studies on the influence of age on immune response to understand the biology of immunosenescence. Exp Gerontol 1998; 33: 27–38

    Article  PubMed  CAS  Google Scholar 

  103. Miller RA. The aging immune system: primer and prospectus. Science 1996; 273: 70–4

    Article  PubMed  CAS  Google Scholar 

  104. Pawelec G, Solana R. Immunosenescence. Immunol Today 1997; 18: 514–6

    Article  PubMed  CAS  Google Scholar 

  105. Burns EA, Goodwin JS. Immunodeficiency of aging. Drugs Aging 1997; 11: 374–97

    Article  PubMed  CAS  Google Scholar 

  106. Haynes BF, Markert ML, Sempowski GD, et al. The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev Immunol 2000; 18: 529–60

    Article  PubMed  CAS  Google Scholar 

  107. Steinmann GG, Klaus B, Muller-Hermelink HK. The involution of the ageing human thymic epithelium is independent of puberty: a morphometric study. Scand J Immunol 1985; 22: 563–75

    Article  PubMed  CAS  Google Scholar 

  108. Steinmann GG. Changes in the human thymus during aging. Curr Top Pathol 1986; 75: 43–88

    Article  PubMed  CAS  Google Scholar 

  109. Aronson M. Hypothesis: involution of the thymus with aging–programmed and beneficial. Thymus 1991; 18: 7–13

    PubMed  CAS  Google Scholar 

  110. Smith SM, Ossa-Gomez LJ. A quantitative histologic comparison of the thymus in 100 healthy and diseased adults. Am J Clin Pathol 1981; 76: 657–65

    PubMed  CAS  Google Scholar 

  111. Bertho JM, Demarquay C, Moulian N, et al. Phenotypic and immunohistological analyses of the human adult thymus: evidence for an active thymus during adult life. Cell Immunol 1997; 179: 30–40

    Article  PubMed  CAS  Google Scholar 

  112. Scollay R, Wilson A, Shortman K. Thymus cell migration: analysis of thymus emigrants with markers that distinguish medullary thymocytes from peripheral T cells. J Immunol 1984; 132: 1089–94

    PubMed  CAS  Google Scholar 

  113. Penit C, Vasseur F. Expansion of mature thymocyte subsets before emigration to the periphery. J Immunol 1997; 159:4848–56

    PubMed  CAS  Google Scholar 

  114. Mackall CL, Bare CV, Granger LA, et al. Thymic-in-dependent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol 1996; 156:4609–16

    PubMed  CAS  Google Scholar 

  115. Mackall CL, Fleisher TA, Brown MR, et al. Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy. Blood 1997; 89: 3700–7

    PubMed  CAS  Google Scholar 

  116. Mackall CL, Hakim FT, Gress RE. T-cell regeneration: all repertoires are not created equal. Immunol Today 1997; 18: 245–51

    Article  PubMed  CAS  Google Scholar 

  117. Mackall CL, Granger L, Sheard MA, et al. T-cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived versus thymic-independent progeny. Blood 1993; 82: 2585–94

    PubMed  CAS  Google Scholar 

  118. Alter-Wolf S, Blomberg BB, Riley RL. Old mice retain bone marrow B1 progenitors, but lose B2 precursors, and exhibit altered immature B cell phenotype and light chain usage. Mech Ageing Dev 2009; 130: 401–8

    Article  PubMed  CAS  Google Scholar 

  119. Prineas JW, McDonald WI. Demyelinating diseases. In: Graham DI, Lantos PL, editors. Greenfield’s neuropathology. New York: Oxford University Press, 1997: 813–96

    Google Scholar 

  120. Raine CS. Demyelinating diseases. In: Davis RL, Robertson DM, editors. Textbook of neuropathology. New York: Williams and Wilkins, 1997: 627–14

    Google Scholar 

  121. Lassmann H, Raine CS, Antel J, et al. Immunopathology of multiple sclerosis: report on an international meeting held at the Institute of Neurology of the University of Vienna. J Neuroimmunol 1998; 86: 213–7

    Article  PubMed  CAS  Google Scholar 

  122. Lucchinetti C, Bruck W, Parisi J, et al. A quantitative analysis of oligodendrocytes in multiple sclerosis lesions: a study of 113 cases. Brain 1999; 122: 2279–95

    Article  PubMed  Google Scholar 

  123. Frischer JM, Bramow S, Dal-Bianco A, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 2009; 132: 1175–89

    Article  PubMed  Google Scholar 

  124. Thompson AJ, Kermode AG, MacManus DG, et al. Pathogenesis of progressive multiple sclerosis. Lancet 1989; 1: 1322–3

    Article  PubMed  CAS  Google Scholar 

  125. de Seze J, Delalande S, Michelin E, et al. Brain MRI in late-onset multiple sclerosis. Eur J Neurol 2005; 12: 241–4

    Article  PubMed  Google Scholar 

  126. Tartaglino LM, Friedman DP, Flanders AE, et al. Multiple sclerosis in the spinal cord: MR appearance and correlation with clinical parameters. Radiology 1995; 195: 725–32

    PubMed  CAS  Google Scholar 

  127. Delalande S, de Seze J, Ferriby D, et al. Late onset MS. Rev Neurol 2002; 158: 1082–7

    PubMed  CAS  Google Scholar 

  128. Stenager EN, Stenager E, Koch-Henriksen N, et al. Suicide and multiple sclerosis: an epidemiological investigation. J Neurol Neurosurg Psychiatry 1992; 55: 542–5

    Article  PubMed  CAS  Google Scholar 

  129. Turner AP, Williams RM, Bowen JD, et al. Suicidal ideation in multiple sclerosis. Arch Phys Med Rehabil 2006; 87: 1073–8

    Article  PubMed  Google Scholar 

  130. Fleming ST, Blake Jr RL. Patterns of comorbidity in elderly patients with multiple sclerosis. J Clin Epidemiol 1994; 47: 1127–32

    Article  PubMed  CAS  Google Scholar 

  131. Allen NB, Lichtman JH, Cohen HW, et al. Vascular disease among hospitalized multiple sclerosis patients. Neuroepidemiology 2008; 30: 234–8

    Article  PubMed  Google Scholar 

  132. Fleming ST. Multiple sclerosis as comorbidity: a study of resource utilization and outcomes of care. Clin Perform Qual Health Care 1995; 3: 23–30

    PubMed  CAS  Google Scholar 

  133. Dal Bianco A, Bradl M, Frischer J, et al. Multiple sclerosis and Alzheimer’s disease. Ann Neurol 2008; 63: 174–83

    Article  Google Scholar 

  134. The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis: I, clinical results of a multi-center, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43: 655–61

    Article  Google Scholar 

  135. Johnson KP, Brooks BR, Cohen JA, et al. Copolymer I reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multi-center, double-blind placebo-controlled trial. Neurology 1995; 45: 1268–76

    Article  PubMed  CAS  Google Scholar 

  136. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis: the Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996; 39: 285–94

    Article  PubMed  CAS  Google Scholar 

  137. European Study Group on Interferon Beta-1b in Secondary Progressive MS. Placebo-controlled multi-center randomized trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet 1998; 352: 1491–7

    Article  Google Scholar 

  138. The Once Weekly Interferon for MS Study Group. Evidence of interferon beta-1a response in relapsing-remitting MS: the OWIMS Study. Neurology 1999; 53: 679–86

    Article  Google Scholar 

  139. Comi G, Filippi M, Wolinsky JS, the European and Canadian Glatiramer Acetate Study Group. European/Canadian multi-center double blind, randomized placebo controlled study of the effects of glatiramer acetate on magnetic resonance imaging measured disease activity and burden in patients with relapsing multiple sclerosis. Ann Neurol 2001; 49: 290–7

    Article  PubMed  CAS  Google Scholar 

  140. Polman C, Barkhof F, Kappos L, et al., European Oral Interferon Beta-1a in Relapsing-Remitting MS Study Group. Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study. Mult Scler 2003; 9: 342–8

    Article  PubMed  CAS  Google Scholar 

  141. Miller DH, Khan OA, Sheremata WA, et al., International Natalizumab Multiple Sclerosis Trial Group. A controlled trial of natalizumab for relapsing MS. N Engl J Med 2003; 348: 15–23

    Article  PubMed  CAS  Google Scholar 

  142. Panitch H, Miller A, Paty D, et al. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 2004; 63: 1788–95

    Article  PubMed  CAS  Google Scholar 

  143. Hemmer B, Frohman E, Hartung HP, et al. Central nervous system infections: a potential complication of systemic immunotherapy. Curr Opin Neurol 2006; 19: 271–6

    Article  PubMed  CAS  Google Scholar 

  144. Le Couteur DG, McLean AJ. The aging liver: drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet 1998; 34: 359–73

    Article  PubMed  Google Scholar 

  145. Mühlberg W, Platt D. Age-dependent changes of the kidneys: pharmacological implications. Gerontology 1999; 45: 243–53

    Article  PubMed  Google Scholar 

  146. Yuan R, Venitz J. Effect of chronic renal failure on the disposition of highly hepatically metabolized drugs. Int J Clin Pharmacol Ther 2000; 38: 243–53

    Google Scholar 

  147. Baldwin Jr JG. Hematopoietic function in the elderly. Ann Intern Med 1988; 148: 2544–6

    Article  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. Olaf Stüve has received honoraria from Teva, EMO Biomedicine and Serono. Amer Awad has no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA

    Amer Awad &  Olaf Stüve

  2. Department of Immunology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA

    Olaf Stüve

  3. Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Road, Dallas, Texas, 75216, USA

    Olaf Stüve

Authors
  1. Amer Awad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olaf Stüve
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olaf Stüve.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Awad, A., Stüve, O. Multiple Sclerosis in the Elderly Patient. Drugs Aging 27, 283–294 (2010). https://doi.org/10.2165/11532120-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11532120-000000000-00000

Keywords

Search

Navigation