, Volume 4, Issue 4, pp 618–626

Corticosteroids for multiple sclerosis: I. Application for treating exacerbations

  • Elliot M. Frohman
  • Anjali Shah
  • Eric Eggenberger
  • Luanne Metz
  • Robert Zivadinov
  • Olaf Stüve
Review Article


Multiple sclerosis (MS) is an inflammatory demyelinating disorder characterized by a multiphasic course of neurological exacerbations, periods of clinical remission, and, in most patients, ultimately progressive deterioration of functional capabilities. The relapsing-remitting phase of the disease involves acute interruption in neurological functioning relating to areas of inflammation in discrete central-tract systems. The treatment of MS exacerbations with anti-inflammatory agents such as corticosteroids and adrenocorticotropic hormone has represented an established practice throughout the neurology community. Although there is scientific rationale supporting application of these agents for this purpose, the broad diversity of approaches to using these drugs in clinical practice is a derivative of expert opinion and anecdotal experience. Ultimately, the treatment of MS-related exacerbations is part science, but mostly art. This review discusses the pharmacology of these agents, to better understand how they may act to mitigate attacks and to provide some practical formulations for how to use them in the clinic for the benefit of patients.

Key Words

Corticosteroids ACTH pulse steroids 


  1. 1.
    Uhthoff W. Untersuchungen über die bei der multiplen Herdsklerose vorkommenden Augenstorungen [In German]. Arch Psychiatr Nervenkrankh 1889;20:55.Google Scholar
  2. 2.
    Hansen BS, Hussain RZ, Lovett-Racke AE, Thomas JA, Racke MK. Multiple toll-like receptor agonists act as potent adjuvants in the induction of autoimmunity. J Neuroimmunol 2006;172:94–103.CrossRefPubMedGoogle Scholar
  3. 3.
    Goodin D, Frohman EM, Garmany GP Jr, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002;58:169–178 [Erratum in: Neurology 2002;59:480].PubMedGoogle Scholar
  4. 4.
    Dalakas MC. Current treatment of the inflammatory myopathies. Curr Opin Rheumatol 1994;6:595–601.CrossRefPubMedGoogle Scholar
  5. 5.
    Kirwan JR; The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 1995;333:142–146.CrossRefPubMedGoogle Scholar
  6. 6.
    Hall S, Conn DL. Immunosuppressive therapy for vasculitis. Curr Opin Rheumatol 1995;7:25–29.PubMedGoogle Scholar
  7. 7.
    Guillevin L, Lhote F. Distinguishing polyarteritis nodosa from microscopic polyangiitis and implications for treatment. Curr Opin Rheumatol 1995;7:20–24.PubMedGoogle Scholar
  8. 8.
    Youssef PP, Haynes DR, Triantafillou S, et al. Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis. Arthritis Rheum 1997;40:1400–1408.CrossRefPubMedGoogle Scholar
  9. 9.
    Droogan AG, Crockard AD, McMillan SA, Hawkins SA. Effects of intravenous methylprednisolone therapy on leukocyte and soluble adhesion molecule expression in MS. Neurology 1998;50:224–229.PubMedGoogle Scholar
  10. 10.
    Filipovic SR, Drulovic J, Stojsavljevic N, Levic Z. The effects of high-dose intravenous methylprednisolone on event-related potentials in patients with multiple sclerosis. J Neurol Sci 1997;152:147–153.CrossRefPubMedGoogle Scholar
  11. 11.
    Patzold T, Schwengelbeck M, Ossege LM, Malin JP, Sindem E. Changes of the MS Functional Composite and EDSS during and after treatment of relapses with methylprednisolone in patients with multiple sclerosis. Acta Neurol Scand 2002; 105:164–168.CrossRefPubMedGoogle Scholar
  12. 12.
    Humm AM, Z’Graggen WJ, Buhler R, Magistris MR, Rosier KM. Quantification of central motor conduction deficits in multiple sclerosis patients before and after treatment of acute exacerbation by methylprednisolone. J Neurol Neurosurg Psychiatry 2006;77:345–350.CrossRefPubMedGoogle Scholar
  13. 13.
    Buttgereit F, Wehling M, Burmester GR. A new hypothesis of modular glucocorticoid actions: steroid treatment of rheumatic diseases revisited. Arthritis Rheum 1998;41:761–767.CrossRefPubMedGoogle Scholar
  14. 14.
    Gold R, Buttgereit F, Toyka KV. Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders. J Neuroimmunol 2001;117:1–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Wehling M. Specific, nongenomic actions of steroid hormones. Annu Rev Physiol 1997;59:365–393.CrossRefPubMedGoogle Scholar
  16. 16.
    Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 1993;119:1198–1208.PubMedGoogle Scholar
  17. 17.
    Adcock IM, Caramori G, Ito K. New insights into the molecular mechanisms of corticosteroids actions. Curr Drug Targets 2006;7:649–660.CrossRefPubMedGoogle Scholar
  18. 18.
    Falkenstein E, Norman AW, Wehling M. Mannheim classification of nongenomically initiated (rapid) steroid action(s). J Clin Endocrinol Metab 2000;85:2072–2075.CrossRefPubMedGoogle Scholar
  19. 19.
    Buttgereit F, Brand MD, Burmester GR. Equivalent doses and relative drug potencies for non-genomic glucocorticoid effects: a novel glucocorticoid hierarchy. Biochem Pharmacol 1999;58:363–368.CrossRefPubMedGoogle Scholar
  20. 20.
    Yong VW, Power C, Forsyth P, Edwards DR. Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2001;2:502–511.CrossRefPubMedGoogle Scholar
  21. 21.
    Rosenberg GA, Dencoff JE, Correa N Jr, Reiners M, Ford CC. Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood-brain barrier injury. Neurology 1996; 46:1626–1632.PubMedGoogle Scholar
  22. 22.
    Orchinik M, Murray TF, Moore FL. A corticosteroid receptor in neuronal membranes. Science 1991;252:1848–1851.CrossRefPubMedGoogle Scholar
  23. 23.
    Gametchu B. Glucocorticoid receptor-like antigen in lymphoma cell membranes: con-elation to cell lysis. Science 1987;236:456–461.CrossRefPubMedGoogle Scholar
  24. 24.
    Gametchu B, Watson CS, Wu S. Use of receptor antibodies to demonstrate membrane glucocorticoid receptor in cells from human leukemic patients. FASEB J 1993;7:1283–1292.PubMedGoogle Scholar
  25. 25.
    Diba F, Watson CS, Gametchu B. 5′UTR sequences of the glucocorticoid receptor 1A transcript encode a peptide associated with translational regulation of the glucocorticoid receptor. J Cell Biochem 2001;81:149–161.CrossRefPubMedGoogle Scholar
  26. 26.
    Chaudhari BR, Murphy RF, Agrawal DK. Following the TRAIL to apoptosis. Immunol Res 2006;35: 249–262.CrossRefPubMedGoogle Scholar
  27. 27.
    Navratil JS, Liu CC, Aheam JM. Apoptosis and autoimmunity. Immunol Res 2006;36:3–12.CrossRefPubMedGoogle Scholar
  28. 28.
    Buttgereit F, Krauss S, Brand MD. Methylprednisolone inhibits uptake of Ca2+ and Na+ ions into concanavalin A-stimulated thymocytes. Biochem J 1997;326:329–332.PubMedGoogle Scholar
  29. 29.
    Schmidt J, Gold R, Schonrock L, Zettl UK, Hartung HP, Toyka KV. T-cell apoptosis in situ in experimental autoimmune enceph-alomyelitis following methylprednisolone pulse therapy. Brain 2000; 123: 1431–1441.CrossRefPubMedGoogle Scholar
  30. 30.
    Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol 1990;8:579–621.CrossRefPubMedGoogle Scholar
  31. 31.
    Levine S, Wenk EJ, Muldoon TN, Cohen SG. Enhancement of experimental allergic encephalomyelitis by adrenalectomy. Proc Soc Exp Biol Med 1962; 111:383–385.PubMedGoogle Scholar
  32. 32.
    McCombe PA, Nickson I, Tabi Z, Pender MP. Corticosteroid treatment of experimental autoimmune encephalomyelitis in the Lewis rat results in loss of V beta 8.2+ and myelin basic protein-reactive cells from the spinal cord, with increased total T-cell apoptosis but reduced apoptosis of V beta 8.2+ cells. J Neuroimmunol 1996;70:93–101.CrossRefPubMedGoogle Scholar
  33. 33.
    Pender MP, Nguyen KB, McCombe PA, Kerr JF. Apoptosis in the nervous system in experimental allergic encephalomyelitis. J Neurol Sci 1991;104:81–87.CrossRefPubMedGoogle Scholar
  34. 34.
    Durelli L, Cocito D, Riccio A, et al. High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations. Neurology 1986;36:238–243.PubMedGoogle Scholar
  35. 35.
    Beck RW, Cleary PA, Anderson MM, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992;326:581–588.CrossRefPubMedGoogle Scholar
  36. 36.
    Sellebjerg F, Frederiksen JL, Nielsen PM, Olesen J. Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS. Neurology 1998;51:529–534.PubMedGoogle Scholar
  37. 37.
    Brusaferri F, Candelise L. Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials. J Neurol 2000;247:435–442.CrossRefPubMedGoogle Scholar
  38. 38.
    Rose AS, Kuzma JW, Kurtzke JF, Namerow NS, Sibley WA, Tourtellotte WW. Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs. placebo—final report. Neurology 1970;20: 1–59.PubMedGoogle Scholar
  39. 39.
    Humm AM, Z’Graggen WJ, Buhler R, Magistris MR, Rosier KM. Quantification of central motor conduction deficits in multiple sclerosis patients before and after treatment of acute exacerbation by methylprednisolone. J Neurol Neurosurg Psychiatry 2006;77:345–50.CrossRefPubMedGoogle Scholar
  40. 40.
    Filippini G, Brusaferri F, Sibley WA, Citterio A, Ciucci G, Midgard R, Candelise L. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis.Google Scholar
  41. 41.
    Ciucci G, Midgard R, Candelise L. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev 2000;(4):CD001331.Google Scholar
  42. 42.
    Hoogervorst EL, Polman CH, Barkhof F. Cerebral volume changes in multiple sclerosis patients treated with high-dose intravenous methylprednisolone. Mult Scler 2002;8:415–419.CrossRefPubMedGoogle Scholar
  43. 43.
    Herishanu YO, Badama S, Sarov B, Abarbanel JM, Segal S, Bearman JE. A possible harmful late effect of methylprednisolone therapy on a time cluster of optic neuritis. Acta Neurol Scand 1989;80:569–574.CrossRefPubMedGoogle Scholar
  44. 44.
    Stüve O, Marra CM, Jerome K, et al. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann Neurol 2006;59:743–747.CrossRefPubMedGoogle Scholar
  45. 45.
    Stiive O, Marra CM, Jerome K, et al. Altered CD4:CD8 T cells ratios in cerebrospinal fluid of natalizumab-treated multiple sclerosis patients. Arch Neurol 2006;63:1383–1387.CrossRefGoogle Scholar
  46. 46.
    Stüve O, Marra CM, Petra CD, et al. The potential risk of progressive multifocal leukoencephalopathy with natalizumab therapy: possible interventions. Arch Neurol 2007;64:169–176.CrossRefPubMedGoogle Scholar
  47. 47.
    Sellebjerg F, Schaldemose Nielsen H, Fredericksen JL, Olesen J. A randomized, controlled trial of oral high-dose methylprednisolone in acute optic neuritis. Neurology 1999;52:1479–1484.PubMedGoogle Scholar
  48. 48.
    Alam SM, Kyriakides T, Lawden M, Newman PK. Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high dose. J Neurol Neurosurg Psychiatry 1993;56:1219–1220.CrossRefPubMedGoogle Scholar
  49. 49.
    Barnes D, Hughes RAC, Morris RW, et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet 1997;349:902–906.CrossRefPubMedGoogle Scholar
  50. 50.
    Metz LM, Sabuda D, Hilsden RJ, Enns R, Meddings JB. Gastric tolerance of high-dose pulse oral prednisone in multiple sclerosis. Neurology 1999;53:2093–2096.PubMedGoogle Scholar
  51. 51.
    Morrow SA, Stoian CA, Dmitrovic J, Chan SC, Metz LM. The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis. Neurology 2004;63:1079–1080.PubMedGoogle Scholar
  52. 52.
    Lackner TE. Interaction of dexamethasone with phenytoin. Pharmacotherapy 1991;11:344–347.PubMedGoogle Scholar
  53. 53.
    Pradat P, Robert-Gnansia E, Di Tanna GL, Rosano A, Lisi A, Mastroiacovo P; Contributors to the MADRE database. First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Terato 2003;67:968–970.CrossRefGoogle Scholar

Copyright information

© Springer New York 2007

Authors and Affiliations

  • Elliot M. Frohman
    • 1
    • 2
  • Anjali Shah
    • 1
    • 2
  • Eric Eggenberger
    • 3
  • Luanne Metz
    • 4
  • Robert Zivadinov
    • 6
  • Olaf Stüve
    • 7
  1. 1.Department of NeurologyUniversity of Texas Southwestern Medical Center at DallasDallas
  2. 2.Department OphthalmologyUniversity of Texas Southwestern Medical Center at DallasDallas
  3. 3.Department of Physical Medicine and RehabilitationUniversity of Texas Southwestern Medical Center at DallasDallas
  4. 4.Department of Neurology and OphthalmologyMichigan State UniversityEast Lansing
  5. 5.Department of Clinical NeurosciencesUniversity of Calgary and Calgary Health RegionCalgaryCanada
  6. 6.Department of Neurology, Buffalo Neuroimaging Analysis Center, The Jacobs Neurological InstituteState University of New York at BuffaloBuffalo
  7. 7.Neurology Section, Medical ServiceVeterans Affairs North Texas Health Care SystemDallas

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