Semin Neurol 2013; 33(01): 074-078
DOI: 10.1055/s-0033-1343798
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Treatment of Primary Progressive Multiple Sclerosis

Orhun Kantarci
1   Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota
› Author Affiliations
Further Information

Publication History

Publication Date:
25 May 2013 (online)

Abstract

Primary progressive multiple sclerosis (MS) is primarily a neurodegenerative phenotype of MS. It is characterized by a predominant progressive disease course that largely determines the disability progression rather than the rare early superimposed relapses. Therefore, frustratingly, the immunomodulatory and immunosuppressive approaches have failed to have any meaningful impact on the disability progression in primary-progressive MS. Some benefit can still be obtained in select patients where notable number of superimposed relapses or significant ongoing subclinical magnetic resonance imaging activity may allow for immunomodulatory agents to work. Symptomatic treatment for MS should also not be overlooked in this population for impact on quality of life. Future work will likely focus more on the remyelinating and regenerative strategies to help this group of patients. Unfortunately, the lack of any warning symptoms hampers any future prevention trial in this population. However, inferring from previous studies in secondary progressive MS, a global effort to eliminate initiation of tobacco smoking in teenagers or young adults may also delay the onset of a progressive disease course in MS.

 
  • References

  • 1 Kremenchutzky M, Rice GP, Baskerville J, Wingerchuk DM, Ebers GC. The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain 2006; 129 (Pt 3) 584-594
  • 2 Tutuncu M, Tang J, Zeid NA , et al. Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis. Mult Scler 2013; 19 (2) 188-198
  • 3 Kappos L, Weinshenker B, Pozzilli C , et al; European (EU-SPMS) Interferon beta-1b in Secondary Progressive Multiple Sclerosis Trial Steering Committee and Independent Advisory Board; North American (NA-SPMS) Interferon beta-1b in Secondary Progressive Multiple Sclerosis Trial Steering Committee and Independent Advisory Board. Interferon beta-1b in secondary progressive MS: a combined analysis of the two trials. Neurology 2004; 63 (10) 1779-1787
  • 4 La Maestra S, Kisby GE, Micale RT , et al. Cigarette smoke induces DNA damage and alters base-excision repair and tau levels in the brain of neonatal mice. Toxicol Sci 2011; 123 (2) 471-479
  • 5 Westlye LT, Walhovd KB, Dale AM , et al. Life-span changes of the human brain white matter: diffusion tensor imaging (DTI) and volumetry. Cereb Cortex 2010; 20 (9) 2055-2068
  • 6 Hasan KM, Kamali A, Abid H, Kramer LA, Fletcher JM, Ewing-Cobbs L. Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography. Brain Struct Funct 2010; 214 (4) 361-373
  • 7 Healy BC, Ali EN, Guttmann CR , et al. Smoking and disease progression in multiple sclerosis. Arch Neurol 2009; 66 (7) 858-864
  • 8 Wolinsky JS, Narayana PA, O'Connor P , et al; PROMiSe Trial Study Group. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 2007; 61 (1) 14-24
  • 9 Wolinsky JS, Shochat T, Weiss S, Ladkani D. PROMiSe Trial Study Group. Glatiramer acetate treatment in PPMS: why males appear to respond favorably. J Neurol Sci 2009; 286 (1-2) 92-98
  • 10 Kantarci OH, Weinshenker BG. Natural history of multiple sclerosis. Neurol Clin 2005; 23 (1) 17-38 , v
  • 11 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 (3) 765-772
  • 12 Johnson KP, Brooks BR, Cohen JA , et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995; 45 (7) 1268-1276
  • 13 Leary SM, Thompson AJ. Interferon beta-1a in primary progressive multiple sclerosis. J Neurol Sci 2003; 206 (2) 215-216
  • 14 Leary SM, Miller DH, Stevenson VL, Brex PA, Chard DT, Thompson AJ. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 2003; 60 (1) 44-51
  • 15 British and Dutch Multiple Sclerosis Azathioprine Trial Group. Double-masked trial of azathioprine in multiple sclerosis. Lancet 1988; 2 (8604) 179-183
  • 16 Goodkin DE, Rudick RA, VanderBrug Medendorp S , et al. Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol 1995; 37 (1) 30-40
  • 17 Rice GP, Filippi M, Comi G. Cladribine MRI Study Group. Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Neurology 2000; 54 (5) 1145-1155
  • 18 Hawker K, O'Connor P, Freedman MS , et al; OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 2009; 66 (4) 460-471
  • 19 Ghatak NR, Leshner RT, Price AC, Felton III WL. Remyelination in the human central nervous system. J Neuropathol Exp Neurol 1989; 48 (5) 507-518
  • 20 Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain 1999; 122 (Pt 12) 2279-2295
  • 21 Miller DJ, Bright JJ, Sriram S, Rodriguez M. Successful treatment of established relapsing experimental autoimmune encephalomyelitis in mice with a monoclonal natural autoantibody. J Neuroimmunol 1997; 75 (1-2) 204-209
  • 22 Murray PD, McGavern DB, Sathornsumetee S, Rodriguez M. Spontaneous remyelination following extensive demyelination is associated with improved neurological function in a viral model of multiple sclerosis. Brain 2001; 124 (Pt 7) 1403-1416