Journal of Neurology

, Volume 257, Issue 11, pp 1806–1811

Intrathecal methotrexate treatment in multiple sclerosis

  • Saud A. Sadiq
  • Elena V. Simon
  • Lauren M. Puccio
Original Communication


This study reports on the feasibility of using intrathecal methotrexate (ITMTX) in treatment unresponsive multiple sclerosis (MS) patients with progressive forms of the disease. A retrospective, open-label, chart review analysis was conducted following patients (n = 121) with MS for up to eight treatments given every 8–11 weeks. Patients were considered for ITMTX treatment if they were unresponsive to or intolerant of FDA-approved treatments. There was a 1 year follow-up after their eighth or last treatment (if discontinued earlier). Patients underwent neurological assessments and expanded disability status scale (EDSS) evaluations. No serious adverse effects were noted during the study period. In 87 secondary progressive MS patients, EDSS scores were stable or improved in 89%, with significantly improved mean EDSS post-treatment compared to baseline (P = 0.014). Of 34 primary progressive patients, EDSS scores were stable in 82%, with no significant progression in EDSS post-treatment compared to baseline. ITMTX may have a beneficial role in progressive forms of MS and is well tolerated with no serious adverse events.


Methotrexate Intrathecal Cerebrospinal fluid Multiple sclerosis 

Supplementary material

415_2010_5614_MOESM1_ESM.doc (29 kb)
Supplementary material 1 (DOC 29 kb)


  1. 1.
    CAMMS223 Trial Investigators, Coles AJ, Crompston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK (2008) Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 359:1786–801Google Scholar
  2. 2.
    Bleyer WA, Poplack DG (1985) Prophylaxis and treatment of leukemia in the central nervous system and other sanctuaries [Review]. Semin Oncol 12:131–148PubMedGoogle Scholar
  3. 3.
    Bornstein MB, Miller A, Slagle S et al (1991) A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Neurology 41:533–539PubMedGoogle Scholar
  4. 4.
    Coffey JR, Cahill D, Steers W et al (1993) Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg 78(2):226–232CrossRefPubMedGoogle Scholar
  5. 5.
    Coles AJ, Cox A, Le Page E et al (2006) The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol 258:98–108CrossRefGoogle Scholar
  6. 6.
    Cronstein BN (2005) Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev 57(2):163–172CrossRefPubMedGoogle Scholar
  7. 7.
    Daumer M, Griffith LM, Meisner W et al (2006) Survival and time to an advanced disease state or progression, of untreated patients with moderately severe multiple sclerosis in a multicenter observational database: relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation. Mult Scler 12:174–179CrossRefPubMedGoogle Scholar
  8. 8.
    Efficacy and safety study of oral BG00012 with active reference in relapsing-remitting multiple sclerosis (CONFIRM). Accessed March 13, 2009 at
  9. 9.
    Fawcett JW, Asher RA (1999) The glial scar and central nervous system repair. Brain Res Bull 49(6):377–391CrossRefPubMedGoogle Scholar
  10. 10.
    Franciotta D, Salvetti M, Lolli F, Serafini B, Aloisi F (2008) B cells and multiple sclerosis. Lancet Neurol 7(9):852–858CrossRefPubMedGoogle Scholar
  11. 11.
    FTY720 in patients with primary progressive multiple sclerosis (INFORMS). Accessed October 7, 2009 at
  12. 12.
    Goodkin DE, Rudick RA, Medendorp SV et al (1995) Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol 37((1):30–40CrossRefPubMedGoogle Scholar
  13. 13.
    Hartung HP, Aktas O (2009) Bleak prospects for primary progressive multiple sclerosis therapy: Downs and downs, but a glimmer of Hope. Ann Neurol 66(4):429–432CrossRefPubMedGoogle Scholar
  14. 14.
    Hartung HP, Gonsette R, Koniq N et al (2002) Mitoxantrone in progressive multiple sclerosis: a placebo controlled, double-blind, randomized, multicentre trial. Lancet 360:2018–2025CrossRefPubMedGoogle Scholar
  15. 15.
    Hauser SL, Waubant E, Arnold DL et al (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358:676–688CrossRefPubMedGoogle Scholar
  16. 16.
    Hawker K (2008) Efficacy and safety of rituximab in primary progressive multiple sclerosis: results of a randomized, double blind, placebo-controlled, multicenter trial. Mult Scler 14:S229Google Scholar
  17. 17.
    Kappos L, Weinshenker B, Pozzilli C et al (2004) Interferon beta-1b in secondary progressive MS: A combined analysis of the two trials. Neurology 63:1779–1787PubMedGoogle Scholar
  18. 18.
    Kuenz B, Lutterotti A, Ehling R et al (2008) Cerebrospinal fluid B cells correlate with early brain inflammation in multiple sclerosis. PLoS ONE 3(7):e2559. doi:10.1371/journal.pone.0002559
  19. 19.
    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMedGoogle Scholar
  20. 20.
    Oral cladribine in early multiple sclerosis (MS) (ORACLE MS). Accessed March 13, 2009 at
  21. 21.
    Secondary progressive efficacy clinical trial of recombinant interferon-beta-1 in MS (SPECTRIMS) study group (2001) Randomized controlled trial of interferon- beta-1a in secondary progressive MS: clinical results. Neurology 56:1496–1504Google Scholar
  22. 22.
    Sadiq SA, Rammal M, Sara G (2008) Chronic myeloid leukemia associated with mitoxantrone treatment in a patient with MS. Mult Scler 14:272–273CrossRefPubMedGoogle Scholar
  23. 23.
    Sadiq SA (2005) Management of spasticity. In: Younger DS (ed) Motor disorders. Lippincott Williams and Wilkins, New York, pp 689–697Google Scholar
  24. 24.
    Sadiq SA (2005) Multiple sclerosis. In: Rowland LP (ed) Merritt’s neurology, 11th edn. Lippincott Williams and Wilkins, Philadelphia, pp 941–963Google Scholar
  25. 25.
    Sadiq SA (2005) Pulsed intrathecal methotrexate use in severe MS. Ann Neurol 58:S60Google Scholar
  26. 26.
    Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F (2004) Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 14:164–174CrossRefPubMedGoogle Scholar
  27. 27.
    Ward JR (1985) Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis. J Rheumatol 12(suppl 12):3–6Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Saud A. Sadiq
    • 1
  • Elena V. Simon
    • 1
    • 2
  • Lauren M. Puccio
    • 1
  1. 1.Multiple Sclerosis Research Center of New YorkNew YorkUSA
  2. 2.University of Vermont College of MedicineBurlingtonUSA

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