Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb. 17 (2):162-173. [QxMD MEDLINE Link].
Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983 Mar. 13(3):227-31. [QxMD MEDLINE Link].
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 Apr. 46(4):907-11. [QxMD MEDLINE Link].
McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul. 50(1):121-7. [QxMD MEDLINE Link].
Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011 Jan 18. 76(3):294-300. [QxMD MEDLINE Link]. [Full Text].
Sanford M, Lyseng-Williamson KA. Subcutaneous recombinant interferon-ß-1a (Rebif®): a review of its use in the treatment of relapsing multiple sclerosis. Drugs. 2011 Oct 1. 71(14):1865-91. [QxMD MEDLINE Link].
Betaseron [package insert]. Montville, NJ: Bayer Healthcare Pharmaceuticals Inc. May 2010.
Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ, Boyko A, Pelletier J, et al. Pegylated interferon ß-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014 Jul. 13(7):657-65. [QxMD MEDLINE Link].
Gilenya [package insert]. East Hanover, NJ: Novartis. September 2010.
Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018 Mar 31. 391 (10127):1263-1273. [QxMD MEDLINE Link].
Comi G, Kappos L, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019 Nov. 18 (11):1009-1020. [QxMD MEDLINE Link].
Cohen JA, Comi G, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019 Nov. 18 (11):1021-1033. [QxMD MEDLINE Link].
Pucci E, Giuliani G, Solari A, et al. Natalizumab for relapsing remitting multiple sclerosis. Cochrane Database Syst Rev. 2011 Oct 5. CD007621. [QxMD MEDLINE Link].
Tysabri [package insert]. South San Francisco, CA: Biogen Idec Inc. 2011.
Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24. 380(9856):1819-28. [QxMD MEDLINE Link].
Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24. 380(9856):1829-39. [QxMD MEDLINE Link].
Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, et al. Alemtuzumab more effective than interferon ß-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012 Apr 3. 78(14):1069-78. [QxMD MEDLINE Link].
Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19. 376 (3):221-234. [QxMD MEDLINE Link].
Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19. 376 (3):209-220. [QxMD MEDLINE Link].
Steinman L, Fox E, Hartung HP, Alvarez E, Qian P, Wray S, et al. Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. N Engl J Med. 2022 Aug 25. 387 (8):704-714. [QxMD MEDLINE Link].
Copaxone [package insert] [package insert]. North Wales, PA: Teva Pharmaceuticals USA. February 2009.
Novantrone [package insert]. Rockland, MA: Serono, Inc. May 2012.
Aubagio (teriflunomide) [package insert]. Cambridge, MA: Genentech Corp. September, 2012. Available at [Full Text].
Jeffrey S. FDA approves third oral agent for MS. March 27, 2013. Medscape Medical News. Available at http://www.medscape.com/viewarticle/781450. Accessed: April 2, 2013.
US Food and Drug Administration. FDA approves new multiple sclerosis treatment: Tecfidera. March 27, 2013. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345528.htm. Accessed: April 2, 2013.
Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 Sep 20. 367(12):1098-107. [QxMD MEDLINE Link]. [Full Text].
Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012 Sep 20. 367(12):1087-97. [QxMD MEDLINE Link]. [Full Text].
Leist TP, Comi G, Cree BA, Coyle PK, Freedman MS, Hartung HP, et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014 Mar. 13 (3):257-67. [QxMD MEDLINE Link].
Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan K, Rieckmann P, Comi G, et al. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study. Mult Scler. 2018 Oct. 24 (12):1594-1604. [QxMD MEDLINE Link].
Jeffrey S. FDA Approves Interferon Autoinjector for MS. Available at http://www.medscape.com/viewarticle/777065. Accessed: February 20, 2013.
Windhagen A, Newcombe J, Dangond F, et al. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med. 1995 Dec 1. 182(6):1985-96. [QxMD MEDLINE Link]. [Full Text].
Huan J, Culbertson N, Spencer L, et al. Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res. 2005 Jul 1. 81(1):45-52. [QxMD MEDLINE Link].
Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008 Jun. 223:87-113. [QxMD MEDLINE Link]. [Full Text].
Minagar A, Jy W, Jimenez JJ, et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. 2001 May 22. 56(10):1319-24. [QxMD MEDLINE Link].
Trapp BD, Vignos M, Dudman J, Chang A, Fisher E, Staugaitis SM, et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. Lancet Neurol. 2018 Aug 21. [QxMD MEDLINE Link].
Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005 Aug 15. 202(4):473-7. [QxMD MEDLINE Link]. [Full Text].
Nielsen NM, Westergaard T, Rostgaard K, et al. Familial risk of multiple sclerosis: a nationwide cohort study. Am J Epidemiol. 2005 Oct 15. 162(8):774-8. [QxMD MEDLINE Link].
Nischwitz S, Muller-Myhsok B, Weber F. Risk conferring genes in multiple sclerosis. FEBS Lett. 2011 Dec 1. 585(23):3789-97. [QxMD MEDLINE Link].
Yeo TW, De Jager PL, Gregory SG, et al. A second major histocompatibility complex susceptibility locus for multiple sclerosis. Ann Neurol. 2007 Mar. 61(3):228-36. [QxMD MEDLINE Link]. [Full Text].
Salvetti M, Giovannoni G, Aloisi F. Epstein-Barr virus and multiple sclerosis. Curr Opin Neurol. 2009 Jun. 22(3):201-6. [QxMD MEDLINE Link].
Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008. 30(3):140-6. [QxMD MEDLINE Link].
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20. 296(23):2832-8. [QxMD MEDLINE Link].
Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008. 30(3):140-6. [QxMD MEDLINE Link].
Islam T, Gauderman WJ, Cozen W, Mack TM. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology. 2007 Jul 24. 69(4):381-8. [QxMD MEDLINE Link].
Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009 Apr. 80(4):392-9. [QxMD MEDLINE Link]. [Full Text].
Zivadinov R, Schirda C, Dwyer MG, et al. Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control study. Int Angiol. 2010 Apr. 29(2):158-75. [QxMD MEDLINE Link].
Study To Evaluate Treating Chronic Cerebrospinal Venous Insufficiency (CCSVI) in Multiple Sclerosis Patients. Available at http://clinicaltrials.gov/ct2/show/NCT01089686. Accessed: 10/4/2010.
Zamboni P, Galeotti R, Menegatti E, et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg. 2009 Dec. 50(6):1348-58.e1-3. [QxMD MEDLINE Link].
Laupacis A, Lillie E, Dueck A, et al. Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a meta-analysis. CMAJ. 2011 Nov 8. 183(16):E1203-12. [QxMD MEDLINE Link]. [Full Text].
Centers for Disease Control and Prevention. FAQs about Hepatitis B Vaccine (Hep B) and Multiple Sclerosis. [Full Text].
National Multiple Sclerosis Society. Vaccination. Available at http://www.nationalmssociety.org/living-with-multiple-sclerosis/healthy-living/vaccinations/index.aspx. Accessed: November 17, 2011.
Noonan CW, Williamson DM, Henry JP, et al. The prevalence of multiple sclerosis in 3 US communities. Prev Chronic Dis. 2010 Jan. 7(1):A12. [QxMD MEDLINE Link]. [Full Text].
National Multiple Sclerosis Society. Who Gets MS?. Available at http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/who-gets-ms/index.aspx. Accessed: 10/04/2010.
Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci. 2001 Apr. 22(2):117-39. [QxMD MEDLINE Link].
Aguirre-Cruz L, Flores-Rivera J, De La Cruz-Aguilera DL, Rangel-Lopez E, Corona T. Multiple sclerosis in Caucasians and Latino Americans. Autoimmunity. 2011 Nov. 44(7):571-5. [QxMD MEDLINE Link].
Matsuda PN, Shumway-Cook A, Bamer AM, Johnson SL, Amtmann D, Kraft GH. Falls in multiple sclerosis. PM R. 2011 Jul. 3(7):624-32; quiz 632. [QxMD MEDLINE Link].
Roodhooft JM. Ocular problems in early stages of multiple sclerosis. Bull Soc Belge Ophtalmol. 2009. 65-8. [QxMD MEDLINE Link].
Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep. 2010 Aug. 33(8):1061-7. [QxMD MEDLINE Link].
Optic Neuritis Study Group. The clinical profile of optic neuritis. Experience of the Optic Neuritis Treatment Trial. Optic Neuritis Study Group. Arch Ophthalmol. 1991 Dec. 109(12):1673-8. [QxMD MEDLINE Link].
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov. 33(11):1444-52. [QxMD MEDLINE Link].
Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec. 58(6):840-6. [QxMD MEDLINE Link].
Lonergan R, Kinsella K, Duggan M, Jordan S, Hutchinson M, Tubridy N. Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?. Mult Scler. 2009 Dec. 15(12):1528-31. [QxMD MEDLINE Link].
Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29. 338(5):278-85. [QxMD MEDLINE Link].
Prashanth LK, Taly AB, Sinha S, Arunodaya GR, Swamy HS. Wilson's disease: diagnostic errors and clinical implications. J Neurol Neurosurg Psychiatry. 2004 Jun. 75(6):907-9. [QxMD MEDLINE Link]. [Full Text].
Barkhof F, Filippi M, Miller DH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain. 1997 Nov. 120 ( Pt 11):2059-69. [QxMD MEDLINE Link].
Bonhomme GR, Waldman AT, Balcer LJ, et al. Pediatric optic neuritis: brain MRI abnormalities and risk of multiple sclerosis. Neurology. 2009 Mar 10. 72(10):881-5. [QxMD MEDLINE Link].
Filippi M. Enhanced magnetic resonance imaging in multiple sclerosis. Mult Scler. 2000 Oct. 6(5):320-6. [QxMD MEDLINE Link].
Filippi M, Bozzali M, Horsfield MA, et al. A conventional and magnetization transfer MRI study of the cervical cord in patients with MS. Neurology. 2000 Jan 11. 54(1):207-13. [QxMD MEDLINE Link].
Filippi M, Yousry TA, Alkadhi H, Stehling M, Horsfield MA, Voltz R. Spinal cord MRI in multiple sclerosis with multicoil arrays: a comparison between fast spin echo and fast FLAIR. J Neurol Neurosurg Psychiatry. 1996 Dec. 61(6):632-5. [QxMD MEDLINE Link]. [Full Text].
Grossman RI, Barkhof F, Filippi M. Assessment of spinal cord damage in MS using MRI. J Neurol Sci. 2000 Jan 15. 172 Suppl 1:S36-9. [QxMD MEDLINE Link].
Neema M, Goldberg-Zimring D, Guss ZD, et al. 3 T MRI relaxometry detects T2 prolongation in the cerebral normal-appearing white matter in multiple sclerosis. Neuroimage. 2009 Jul 1. 46(3):633-41. [QxMD MEDLINE Link]. [Full Text].
Poonawalla AH, Hou P, Nelson FA, Wolinsky JS, Narayana PA. Cervical Spinal Cord Lesions in Multiple Sclerosis: T1-weighted Inversion-Recovery MR Imaging with Phase-Sensitive Reconstruction. Radiology. 2008 Jan. 246(1):258-264. [QxMD MEDLINE Link].
Stankiewicz JM, Glanz BI, Healy BC, et al. Brain MRI lesion load at 1.5T and 3T versus clinical status in multiple sclerosis. J Neuroimaging. 2011 Apr. 21(2):e50-6. [QxMD MEDLINE Link]. [Full Text].
Vaneckova M, Seidl Z, Krasensky J, et al. Patients' stratification and correlation of brain magnetic resonance imaging parameters with disability progression in multiple sclerosis. Eur Neurol. 2009. 61(5):278-84. [QxMD MEDLINE Link].
Wattjes MP, Barkhof F. High field MRI in the diagnosis of multiple sclerosis: high field-high yield?. Neuroradiology. 2009 May. 51(5):279-92. [QxMD MEDLINE Link].
[Guideline] Traboulsee, A. et al. Revised Recommendations of the CMSC Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-up of Multiple Sclerosis. Consortim of Multiple Sclerosis Centers. Available at http://c.ymcdn.com/sites/www.mscare.org/resource/collection/9C5F19B9-3489-48B0-A54B-623A1ECEE07B/MRIprotocol2015.pdf. Accessed: August 13, 2015.
Agosta F, Absinta M, Sormani MP, et al. In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study. Brain. 2007 Aug. 130:2211-9. [QxMD MEDLINE Link].
Fazekas F, Offenbacher H, Fuchs S, et al. Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology. 1988 Dec. 38(12):1822-5. [QxMD MEDLINE Link].
Zivadinov R, Tavazzi E, Bergsland N, Hagemeier J, Lin F, Dwyer MG, et al. Brain Iron at Quantitative MRI Is Associated with Disability in Multiple Sclerosis. Radiology. 2018 Jul 17. 180136. [QxMD MEDLINE Link].
Colorado RA, Shukla K, Zhou Y, Wolinsky JS, Narayana PA. Multi-task functional MRI in multiple sclerosis patients without clinical disability. Neuroimage. 2012 Jan 2. 59(1):573-81. [QxMD MEDLINE Link]. [Full Text].
Wang J, Xiao Y, Luo M, Zhang X, Luo H. Statins for multiple sclerosis. Cochrane Database Syst Rev. 2010 Dec 8. CD008386. [QxMD MEDLINE Link].
Arnold DL, Matthews PM, Francis G, Antel J. Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990 Apr. 14(1):154-9. [QxMD MEDLINE Link].
Henning A, Schar M, Kollias SS, Boesiger P, Dydak U. Quantitative magnetic resonance spectroscopy in the entire human cervical spinal cord and beyond at 3T. Magn Reson Med. 2008 Jun. 59(6):1250-8. [QxMD MEDLINE Link].
Marliani AF, Clementi V, Albini-Riccioli L, Agati R, Leonardi M. Quantitative proton magnetic resonance spectroscopy of the human cervical spinal cord at 3 Tesla. Magn Reson Med. 2007 Jan. 57(1):160-3. [QxMD MEDLINE Link].
Berg D, Maurer M, Warmuth-Metz M, Rieckmann P, Becker G. The correlation between ventricular diameter measured by transcranial sonography and clinical disability and cognitive dysfunction in patients with multiple sclerosis. Arch Neurol. 2000 Sep. 57(9):1289-92. [QxMD MEDLINE Link].
Walter U, Wagner S, Horowski S, Benecke R, Zettl UK. Transcranial brain sonography findings predict disease progression in multiple sclerosis. Neurology. 2009 Sep 29. 73(13):1010-7. [QxMD MEDLINE Link].
Vazquez-Marrufo M, Gonzalez-Rosa JJ, Vaquero E, et al. Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients. BMC Neurol. 2008 Nov 24. 8:44. [QxMD MEDLINE Link]. [Full Text].
Jeffrey S. TOPIC: Teriflunomide Delays Clinically Definite MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/803177. Accessed: May 8, 2013.
Rodriguez M, Karnes WE, Bartleson JD, Pineda AA. Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology. 1993 Jun. 43(6):1100-4. [QxMD MEDLINE Link].
Spelman T, Mekhael L, Burke T, Butzkueven H, Hodgkinson S, Havrdova E, et al. Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis. Eur J Neurol. 2016 Jan 19. [QxMD MEDLINE Link].
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):655-61. [QxMD MEDLINE Link].
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 Mar. 39(3):285-94. [QxMD MEDLINE Link].
Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998 Nov 7. 352(9139):1498-504. [QxMD MEDLINE Link].
Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology. 2002 Nov 26. 59(10):1496-506. [QxMD MEDLINE Link].
Schwid SR, Panitch HS. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon beta-1a for relapsing multiple sclerosis. Clin Ther. 2007 Sep. 29(9):2031-48. [QxMD MEDLINE Link].
Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, 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 Jul. 45(7):1268-76. [QxMD MEDLINE Link].
Johnson KP, Brooks BR, Ford CC, et al. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult Scler. 2000 Aug. 6(4):255-66. [QxMD MEDLINE Link].
Khan O, Rieckmann P, Boyko A, Selmaj K, Zivadinov R. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol. 2013 Jun. 73(6):705-13. [QxMD MEDLINE Link].
Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2. 354(9):899-910. [QxMD MEDLINE Link].
Cadavid D, Jurgensen S, Lee S. Impact of natalizumab on ambulatory improvement in secondary progressive and disabled relapsing-remitting multiple sclerosis. PLoS One. 2013. 8(1):e53297. [QxMD MEDLINE Link]. [Full Text].
Chun J, Brinkmann V. A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya). Discov Med. 2011 Sep. 12(64):213-28. [QxMD MEDLINE Link].
Hughes S. Shorter washout reduces MS relapse switching off natalizumab. Medscape Medical News. October 7, 2013. [Full Text].
Hughes S. Shorter Washout Better for Natalizumab-to-Fingolimod Switch. Medscape Medical News. Available at http://www.medscape.com/viewarticle/822567. Accessed: April 1, 2014.
Cohen M, Maillart E, Tourbah A, De Sèze J, Vukusic S, Brassat D, et al. Switching From Natalizumab to Fingolimod in Multiple Sclerosis: A French Prospective Study. JAMA Neurol. 2014 Feb 24. [QxMD MEDLINE Link].
O'Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011 Oct 6. 365(14):1293-303. [QxMD MEDLINE Link].
Semedo, D. Aubagio (Teriflunomide) Slows Brain Atrophy in Patients with Relapsing Multiple Sclerosis. Multiple Sclerosis News Today. Available at http://multiplesclerosisnewstoday.com/2015/10/08/aubagio-teriflunomide-slows-brain-atrophy-patients-relapsing-multiple-sclerosis/. October 8, 2015; Accessed: October 14, 2015.
A study comparing the effectiveness and safety of teriflunomide and interferon beta-1a in patients with relapsing multiple sclerosis (TENERE). 4th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). June 2, 2012 (ClinicalTrials.gov identifier: NCT00883337).
A multicenter double-blind parallel-group placebo-controlled study of the efficacy and safety of teriflunomide in patients with relapsing multiple sclerosis who are treated with interferon-beta. (ClinicalTrials.gov identifier: NCT01252355).
Fox EJ, Sullivan HC, Gazda SK, et al. A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis. Eur J Neurol. 2012 Feb. 19(2):307-11. [QxMD MEDLINE Link].
Anderson P. Alemtuzumab Benefits Hard-to-Treat MS Patients. Medscape Medical News. Available at http://www.medscape.com/viewarticle/805173. Accessed: June 12, 2013.
Brauser, D. Ocrelizumab Linked to Improved Visual Outcomes in Relapsing MS. Medscape Medical News. Available at https://www.medscape.com/viewarticle/887722. October 27, 2017; Accessed: October 27, 2017.
Kesimpta [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation. August 2020. Available at [Full Text].
Harrison DM, Gladstone DE, Hammond E, et al. Treatment of relapsing-remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance. Mult Scler. 2012 Feb. 18(2):202-9. [QxMD MEDLINE Link].
Rojas JI, Romano M, Ciapponi A, Patrucco L, Cristiano E. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21. CD006643. [QxMD MEDLINE Link].
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 Jan. 37(1):30-40. [QxMD MEDLINE Link].
Kappos L, Radue EW, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4. 362(5):387-401. [QxMD MEDLINE Link].
Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4. 362(5):402-15. [QxMD MEDLINE Link].
Khatri B, Barkhof F, Comi G, et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011 Jun. 10(6):520-9. [QxMD MEDLINE Link].
Killestein J, Rudick RA, Polman CH. Oral treatment for multiple sclerosis. Lancet Neurol. 2011 Nov. 10(11):1026-34. [QxMD MEDLINE Link].
Multiple Sclerosis Association of America (MSAA). MS Research Update. Available at http://mymsaa.org/PDFs/MSAA_Research_Update_2013.pdf. Accessed: March 27, 2013.
Anderson P. Myelin peptide skin patch safe, reduces MS activity. Medscape Medical News. July 29, 2013. [Full Text].
Walczak A, Siger M, Ciach A, Szczepanik M, Selmaj K. Transdermal application of myelin peptides in multiple sclerosis treatment. JAMA Neurol. 2013 Jul 1. 1-6. [QxMD MEDLINE Link].
Muraro PA, Pasquini M, Atkins HL, Bowen JD, Farge D, et al. Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurol. 2017 Feb 20. [QxMD MEDLINE Link].
Herman AO. "Unprecedented" Findings for Stem Cell Therapy in MS. NEJM Journal Watch. Available at https://www.jwatch.org/fw113985/2018/03/21/unprecedented-findings-stem-cell-therapy-ms. March 21, 2018; Accessed: March 28, 2018.
Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998 Jul 30. 339(5):285-91. [QxMD MEDLINE Link].
Tsui A, Lee MA. Multiple sclerosis and pregnancy. Curr Opin Obstet Gynecol. 2011 Dec. 23(6):435-9. [QxMD MEDLINE Link].
Krupp LB, Christodoulou C, Melville P, et al. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology. 2011 Apr 26. 76(17):1500-7. [QxMD MEDLINE Link]. [Full Text].
Attarian HP, Brown KM, Duntley SP, Carter JD, Cross AH. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch Neurol. 2004 Apr. 61(4):525-8. [QxMD MEDLINE Link].
MacAllister WS, Krupp LB. Multiple sclerosis-related fatigue. Phys Med Rehabil Clin N Am. 2005 May. 16(2):483-502. [QxMD MEDLINE Link].
Solaro C, Uccelli MM. Management of pain in multiple sclerosis: a pharmacological approach. Nat Rev Neurol. 2011 Aug 16. 7(9):519-27. [QxMD MEDLINE Link].
Goodman AD, Brown TR, Krupp LB, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28. 373(9665):732-8. [QxMD MEDLINE Link].
Ampyra [package insert]. Hawthorne, NY: Acorda Therapeutics, Inc. 2010.
Nicholas RS, Friede T, Hollis S, Young CA. Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21. CD004193. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA approves Botox to treat specific form of urinary incontinence. August 25, 2011. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269509.htm. Accessed: November 28, 2011.
Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27. 326(9):581-8. [QxMD MEDLINE Link].
Myhr KM. Vitamin D treatment in multiple sclerosis. J Neurol Sci. 2009 Nov 15. 286(1-2):104-8. [QxMD MEDLINE Link].
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. November 30, 2010. Available at http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed: December 29, 2011.
Summerday NM, Brown SJ, Allington DR, Rivey MP. Vitamin D and multiple sclerosis: review of a possible association. J Pharm Pract. 2012 Feb. 25(1):75-84. [QxMD MEDLINE Link].
Jagannath VA, Fedorowicz Z, Asokan GV, Robak EW, Whamond L. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. 2010 Dec 8. CD008422. [QxMD MEDLINE Link].
DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol. 2003 Apr. 60(4):504-9. [QxMD MEDLINE Link].
Confavreux C, Suissa S, Saddier P, Bourdès V, Vukusic S. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med. 2001 Feb 1. 344(5):319-26. [QxMD MEDLINE Link].
Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011 Oct. 68(10):1267-71. [QxMD MEDLINE Link].
Rovira À, Wattjes MP, Tintoré M, Tur C, Yousry TA, Sormani MP, et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process. Nat Rev Neurol. 2015 Aug. 11 (8):471-82. [QxMD MEDLINE Link].
[Guideline] Filippi M, Rocca A, Arnold DL, Bakshi R, Barkhof F, De Stefano N, et al. Use of Imaging in Multiple Sclerosis. Gilhus NE, Barnes MP, Brainin M. European Handbook of Neurological Management. 2nd ed. Oxford (UK): Wiley-Blackwell; 2011. Vol 1: 35-51.
Wattjes MP, Rovira À, Miller D, Yousry TA, Sormani MP, de Stefano MP, et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis--establishing disease prognosis and monitoring patients. Nat Rev Neurol. 2015 Oct. 11 (10):597-606. [QxMD MEDLINE Link].
[Guideline] Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence: A Consensus Paper. The Consortium of Multiple Sclerosis Centers. Available at http://www.mscare.org/?page=dmt. July 2014;
Hughes, S. European MS Treatment Guidelines Released. Medscape Medical News. Available at https://www.medscape.com/viewarticle/887730. October 27, 2017; Accessed: October 27, 2017.
Jeffrey S. New AAN Guidelines Advocate Early MS Treatment. Medscape Medical News. Available at https://www.medscape.com/viewarticle/895598. April 23, 2018; Accessed: April 23, 2018.
Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BAC, Gronseth GS, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Apr 24. 90 (17):777-788. [QxMD MEDLINE Link].
Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BAC, Gronseth GS, et al. Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Apr 24. 90 (17):789-800. [QxMD MEDLINE Link].
[Guideline] Farez MF, Correale J, Armstrong MJ, Rae-Grant A, Gloss D, Donley D, et al. Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2019 Sep 24. 93 (13):584-594. [QxMD MEDLINE Link].
Azasan [package insert] [package insert]. Wilmington, NC: Salix pharmaceuticals Inc. August 2011.
Cyclophosphamide [package insert]. Deerfield, IL: Baxter Healthcare Corporation. June 2004.
Brooks M. New AAN guideline on psychiatric disorders in MS. Medscape Medical News. January 3, 2014. [Full Text].
Hughes S. New Test to Identify PML Risk With Natalizumab in MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/832504. Accessed: October 7, 2014.
Jeffrey S. No Cognitive Disadvantage in Pediatric- vs Adult-Onset MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/831536. Accessed: September 15, 2014.
Keller DM. Fingolimod Reduces Annual Brain Volume Loss in MS. Medscape Medical News. Jun 6 2014. [Full Text].
Minden SL, Feinstein A, Kalb RC, Miller D, Mohr DC, Patten SB, et al. Evidence-based guideline: Assessment and management of psychiatric disorders in individuals with MS: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013 Dec 27. [QxMD MEDLINE Link].

Media Gallery

The mechanism of demyelination in multiple sclerosis may be activation of myelin-reactive T cells in the periphery, which then express adhesion molecules, allowing their entry through the blood-brain barrier (BBB). T cells are activated following antigen presentation by antigen-presenting cells such as macrophages and microglia, or B cells. Perivascular T cells can secrete proinflammatory cytokines, including interferon gamma and tumor necrosis factor alpha. Antibodies against myelin also may be generated in the periphery or intrathecally. Ongoing inflammation leads to epitope spread and recruitment of other inflammatory cells (ie, bystander activation). The T cell receptor recognizes antigen in the context of human leukocyte antigen molecule presentation and also requires a second event (ie, co-stimulatory signal via the B7-CD28 pathway, not shown) for T cell activation to occur. Activated microglia may release free radicals, nitric oxide, and proteases that may contribute to tissue damage.
MRI of the head of a 35-year-old man with relapsing-remitting multiple sclerosis. MRI reveals multiple lesions with high T2 signal intensity and one large white matter lesion. These demyelinating lesions may sometimes mimic brain tumors because of the associated edema and inflammation.
MRI of the head of a 35-year-old man with relapsing-remitting multiple sclerosis. This MRI, performed 3 months after the one in the related image, shows a dramatic decrease in the size of lesions.
Inflammation in multiple sclerosis. Hematoxylin and eosin (H&E) stain shows perivascular infiltration of inflammatory cells. These infiltrates are composed of activated T cells, B cells, and macrophages.
Demyelination in multiple sclerosis. Luxol fast blue (LFB)/periodic acid-Schiff (PAS) stain confers an intense blue to myelin. Loss of myelin is demonstrated in this chronic plaque. Note that absence of inflammation may be demonstrated at the edge of chronic lesions.
Gadolinium-enhanced, T1-weighted image showing enhancement of the left optic nerve (arrow).
Corresponding axial images of the spinal cord showing enhancing plaque (arrow). The combination of optic neuritis and longitudinally extensive spinal cord lesions constitutes Devic neuromyelitis optica.

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Table 1. 2017 Revised McDonald Criteria for the Diagnosis of Multiple Sclerosis^[1]

Table 1. 2017 Revised McDonald Criteria for the Diagnosis of Multiple Sclerosis ^[1]

Clinical Presentation	Additional Data Needed for MS Diagnosis
Two or more attacks Objective clinical evidence of 2 or more lesions with reasonable historical evidence of a prior attack	None; clinical evidence will suffice. Additional evidence (eg, brain MRI) desirable, but must be consistent with MS
Two or more attacks Objective clinical evidence of 1 lesion	Dissemination in space demonstrated by MRI or Await further clinical attack implicating a different site
One attack Objective clinical evidence of 2 or more lesions	Dissemination in time demonstrated by MRI or second clinical attack or demonstration of CSF-specific oligoclonal bands
One attack Objective clinical evidence of 1 lesion (clinically isolated syndrome)	Dissemination in space demonstrated by MRI or await a second clinical attack implicating a different CNS site and Dissemination in time, demonstrated by MRI or second clinical attack
· Insidious neurologic progression suggestive of MS	One year of disease progression and dissemination in space, demonstrated by 2 of the following: One or more T2 lesions in brain, in regions characteristic of MS Two or more T2 focal lesions in spinal cord Positive CSF
Notes: An attack is defined as a neurologic disturbance of the kind seen in MS. It can be documented by subjective report or by objective observation, but it must last for at least 24 hours. Pseudoattacks and single paroxysmal episodes must be excluded. To be considered separate attacks, at least 30 days must elapse between onset of one event and onset of another event.

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Author

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Fernando Dangond, MD, FAAN Head of US Medical Affairs, Neurodegenerative Diseases, EMD Serono, Inc

Fernando Dangond, MD, FAAN is a member of the following medical societies: American Academy of Neurology, American Medical Association

Disclosure: Received salary from EMD Serono, Inc. for employment.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Martin K Childers, DO, PhD Professor, Department of Neurology, Wake Forest University School of Medicine; Professor, Rehabilitation Program, Institute for Regenerative Medicine, Wake Forest Baptist Medical Center

Martin K Childers, DO, PhD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Congress of Rehabilitation Medicine, American Osteopathic Association, Christian Medical & Dental Society, and Federation of American Societies for Experimental Biology

Disclosure: Allergan pharma Consulting fee Consulting

Edmond A Hooker II, MD, DrPH, FAAEM Assistant Professor, Department of Emergency Medicine, University of Cincinnati College of Medicine

Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Public Health Association, Society for Academic Emergency Medicine, and Southern Medical Association