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. 2005 Sep;81(959):556–561. doi: 10.1136/pgmj.2004.031294

Diagnosis and disease modifying treatments in multiple sclerosis

J Zajicek 1
PMCID: PMC1743353  PMID: 16143683

Abstract

Multiple sclerosis (MS) refers to scattered areas of hardening found on sectioning central nervous system tissue of affected people, usually after many years of illness. It rarely causes early death but is the commonest cause of neurological disability among young people. Overall results from controlled trials over the past 50 years have been rather disappointing but the comparatively recent licensing of drugs such as interferon beta and glatiramer acetate has led to a reappraisal of many aspects of MS. There are now new diagnostic criteria, which encompass developments in magnetic resonance imaging. Older clinical methods of measuring disease impact are now being re-evaluated to facilitate clinical trials of the approximate 150 new products currently being developed as potential disease modifying agents. The success and failure of agents that should be effective on theoretical grounds, together with advances in neuropathology, have led to fundamental questions regarding our basic understanding of disease pathogenesis being re-addressed.

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Selected References

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  1. Barnett Michael H., Prineas John W. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol. 2004 Apr;55(4):458–468. doi: 10.1002/ana.20016. [DOI] [PubMed] [Google Scholar]
  2. Brex Peter A., Ciccarelli Olga, O'Riordan Jonathon I., Sailer Michael, Thompson Alan J., Miller David H. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med. 2002 Jan 17;346(3):158–164. doi: 10.1056/NEJMoa011341. [DOI] [PubMed] [Google Scholar]
  3. Coles A. J., Wing M., Smith S., Coraddu F., Greer S., Taylor C., Weetman A., Hale G., Chatterjee V. K., Waldmann H. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet. 1999 Nov 13;354(9191):1691–1695. doi: 10.1016/S0140-6736(99)02429-0. [DOI] [PubMed] [Google Scholar]
  4. Comi G., Filippi M., Barkhof F., Durelli L., Edan G., Fernández O., Hartung H., Seeldrayers P., Sørensen P. S., Rovaris M. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet. 2001 May 19;357(9268):1576–1582. doi: 10.1016/s0140-6736(00)04725-5. [DOI] [PubMed] [Google Scholar]
  5. Fox C. M., Bensa S., Bray I., Zajicek J. P. The epidemiology of multiple sclerosis in Devon: a comparison of the new and old classification criteria. J Neurol Neurosurg Psychiatry. 2004 Jan;75(1):56–60. [PMC free article] [PubMed] [Google Scholar]
  6. Hohlfeld R. Biotechnological agents for the immunotherapy of multiple sclerosis. Principles, problems and perspectives. Brain. 1997 May;120(Pt 5):865–916. doi: 10.1093/brain/120.5.865. [DOI] [PubMed] [Google Scholar]
  7. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology. 1995 Jul;45(7):1277–1285. [PubMed] [Google Scholar]
  8. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology. 1993 Apr;43(4):655–661. doi: 10.1212/wnl.43.4.655. [DOI] [PubMed] [Google Scholar]
  9. Jacobs L. D., Beck R. W., Simon J. H., Kinkel R. P., Brownscheidle C. M., Murray T. J., Simonian N. A., Slasor P. J., Sandrock A. W. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med. 2000 Sep 28;343(13):898–904. doi: 10.1056/NEJM200009283431301. [DOI] [PubMed] [Google Scholar]
  10. Jacobs L. D., Cookfair D. L., Rudick R. A., Herndon R. M., Richert J. R., Salazar A. M., Fischer J. S., Goodkin D. E., Granger C. V., Simon J. H. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG) Ann Neurol. 1996 Mar;39(3):285–294. doi: 10.1002/ana.410390304. [DOI] [PubMed] [Google Scholar]
  11. Johnson K. P., Brooks B. R., Cohen J. A., Ford C. C., Goldstein J., Lisak R. P., Myers L. W., Panitch H. S., Rose J. W., Schiffer R. B. 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 Jul;45(7):1268–1276. doi: 10.1212/wnl.45.7.1268. [DOI] [PubMed] [Google Scholar]
  12. 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 Dec;122(Pt 12):2279–2295. doi: 10.1093/brain/122.12.2279. [DOI] [PubMed] [Google Scholar]
  13. McDonald W. I., Compston A., Edan G., Goodkin D., Hartung H. P., Lublin F. D., McFarland H. F., Paty D. W., Polman C. H., Reingold S. C. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul;50(1):121–127. doi: 10.1002/ana.1032. [DOI] [PubMed] [Google Scholar]
  14. Miller David H., Khan Omar A., Sheremata William A., Blumhardt Lance D., Rice George P. A., Libonati Michele A., Willmer-Hulme Allison J., Dalton Catherine M., Miszkiel Katherine A., O'Connor Paul W. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003 Jan 2;348(1):15–23. doi: 10.1056/NEJMoa020696. [DOI] [PubMed] [Google Scholar]
  15. Mumford C. J., Wood N. W., Kellar-Wood H., Thorpe J. W., Miller D. H., Compston D. A. The British Isles survey of multiple sclerosis in twins. Neurology. 1994 Jan;44(1):11–15. doi: 10.1212/wnl.44.1.11. [DOI] [PubMed] [Google Scholar]
  16. Noseworthy J. H., O'Brien P., Erickson B. J., Lee D., Sneve D., Ebers G. C., Rice G. P., Auty A., Hader W. J., Kirk A. The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis. Neurology. 1998 Nov;51(5):1342–1352. doi: 10.1212/wnl.51.5.1342. [DOI] [PubMed] [Google Scholar]
  17. Sawcer Stephen, Maranian Mel, Setakis Efrosini, Curwen Val, Akesson Eva, Hensiek Anke, Coraddu Francesca, Roxburgh Richard, Sawcer David, Gray Julia. A whole genome screen for linkage disequilibrium in multiple sclerosis confirms disease associations with regions previously linked to susceptibility. Brain. 2002 Jun;125(Pt 6):1337–1347. doi: 10.1093/brain/awf143. [DOI] [PubMed] [Google Scholar]
  18. Selmaj K. W., Raine C. S. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol. 1988 Apr;23(4):339–346. doi: 10.1002/ana.410230405. [DOI] [PubMed] [Google Scholar]
  19. Stocchi Fabrizio, Olanow C. Warren. Neuroprotection in Parkinson's disease: clinical trials. Ann Neurol. 2003;53 (Suppl 3):S87–S99. doi: 10.1002/ana.10488. [DOI] [PubMed] [Google Scholar]
  20. Sudlow Cathie L. M., Counsell Carl E. Problems with UK government's risk sharing scheme for assessing drugs for multiple sclerosis. BMJ. 2003 Feb 15;326(7385):388–392. doi: 10.1136/bmj.326.7385.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tintoré M., Rovira A., Martínez M. J., Rio J., Díaz-Villoslada P., Brieva L., Borrás C., Grivé E., Capellades J., Montalban X. Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. AJNR Am J Neuroradiol. 2000 Apr;21(4):702–706. [PMC free article] [PubMed] [Google Scholar]
  22. Trapp B. D., Peterson J., Ransohoff R. M., Rudick R., Mörk S., Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29;338(5):278–285. doi: 10.1056/NEJM199801293380502. [DOI] [PubMed] [Google Scholar]
  23. Willer C. J., Dyment D. A., Risch N. J., Sadovnick A. D., Ebers G. C., Canadian Collaborative Study Group Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci U S A. 2003 Oct 20;100(22):12877–12882. doi: 10.1073/pnas.1932604100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zajicek J. P., Wing M., Scolding N. J., Compston D. A. Interactions between oligodendrocytes and microglia. A major role for complement and tumour necrosis factor in oligodendrocyte adherence and killing. Brain. 1992 Dec;115(Pt 6):1611–1631. [PubMed] [Google Scholar]
  25. Zajicek John, Fox Patrick, Sanders Hilary, Wright David, Vickery Jane, Nunn Andrew, Thompson Alan, UK MS Research Group Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003 Nov 8;362(9395):1517–1526. doi: 10.1016/S0140-6736(03)14738-1. [DOI] [PubMed] [Google Scholar]

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