Multiple sclerosis medical therapy: Difference between revisions

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__NOTOC__
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{{Template:Multiple sclerosis}}
{{Template:Multiple sclerosis}}
{{CMG}}
{{CMG}}; {{AE}} {{Fs}}


==Overview==
==Overview==
The predominant therapy for multiple sclerosis is disease-modifying treatment in relapsing-remitting multiple sclerosis,  [[Immunosuppression|immunosuppressive threpay]] in progressive multiple sclerosis and [[Glucocorticoid]] therapy in acute [[exacerbation]].


==Medical Therapy==
==Medical Therapy==
The predominant therapy for multiple sclerosis is:


=== Disease-modifying treatment of relapsing-remitting multiple sclerosis: ===
=== Disease-modifying treatment of relapsing-remitting multiple sclerosis ===
Relapsing-remitting type of [[MS]] can be treated with disease modifying therapy (DMT) in order to reduce the rate of attack and [[disease]] progression.<ref name="pmid28080255">{{cite journal |vauthors=Capra R, Cordioli C, Rasia S, Gallo F, Signori A, Sormani MP |title=Assessing long-term prognosis improvement as a consequence of treatment pattern changes in MS |journal=Mult. Scler. |volume=23 |issue=13 |pages=1757–1761 |date=November 2017 |pmid=28080255 |doi=10.1177/1352458516687402 |url=}}</ref><ref name="pmid27683916">{{cite journal |vauthors=Lizak N, Lugaresi A, Alroughani R, Lechner-Scott J, Slee M, Havrdova E, Horakova D, Trojano M, Izquierdo G, Duquette P, Girard M, Prat A, Grammond P, Hupperts R, Grand'Maison F, Sola P, Pucci E, Bergamaschi R, Oreja-Guevara C, Van Pesch V, Ramo C, Spitaleri D, Iuliano G, Boz C, Granella F, Olascoaga J, Verheul F, Rozsa C, Cristiano E, Flechter S, Hodgkinson S, Amato MP, Deri N, Jokubaitis V, Spelman T, Butzkueven H, Kalincik T |title=Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis |journal=J. Neurol. Neurosurg. Psychiatry |volume=88 |issue=3 |pages=196–203 |date=March 2017 |pmid=27683916 |doi=10.1136/jnnp-2016-313976 |url=}}</ref>
Relapsing-remitting type of [[MS]] can be treated with disease modifying therapy (DMT) in order to reduce the rate of attack and [[disease]] progression.<ref name="pmid28080255">{{cite journal |vauthors=Capra R, Cordioli C, Rasia S, Gallo F, Signori A, Sormani MP |title=Assessing long-term prognosis improvement as a consequence of treatment pattern changes in MS |journal=Mult. Scler. |volume=23 |issue=13 |pages=1757–1761 |date=November 2017 |pmid=28080255 |doi=10.1177/1352458516687402 |url=}}</ref><ref name="pmid27683916">{{cite journal |vauthors=Lizak N, Lugaresi A, Alroughani R, Lechner-Scott J, Slee M, Havrdova E, Horakova D, Trojano M, Izquierdo G, Duquette P, Girard M, Prat A, Grammond P, Hupperts R, Grand'Maison F, Sola P, Pucci E, Bergamaschi R, Oreja-Guevara C, Van Pesch V, Ramo C, Spitaleri D, Iuliano G, Boz C, Granella F, Olascoaga J, Verheul F, Rozsa C, Cristiano E, Flechter S, Hodgkinson S, Amato MP, Deri N, Jokubaitis V, Spelman T, Butzkueven H, Kalincik T |title=Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis |journal=J. Neurol. Neurosurg. Psychiatry |volume=88 |issue=3 |pages=196–203 |date=March 2017 |pmid=27683916 |doi=10.1136/jnnp-2016-313976 |url=}}</ref>


==== Infusion therapy: ====
==== Infusion therapy: ====
* '''[[Natalizumab]]:''' This [[drug]] works as an [[antibody]] against alpha 4 subunit of [[integrin]]. As a result of [[Blood brain barrier]] disruption, [[inflammatory cells]] like [[Lymphocyte|lymphocytes]] and [[Monocyte|monocytes]] can access [[brain]] parenchyma and start the process of [[inflammation]] and destruction. [[Integrin]] 4 is on the surface of these [[inflammatory cells]] and helps their adhesion to [[vascular]] [[endothelium]]. Based on some studies using this drug can reduce [[signs]], [[Symptom|symptoms]] and relapses of the [[disease]].<ref name="pmid15851719">{{cite journal |vauthors=Rice GP, Hartung HP, Calabresi PA |title=Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale |journal=Neurology |volume=64 |issue=8 |pages=1336–42 |date=April 2005 |pmid=15851719 |doi=10.1212/01.WNL.0000158329.30470.D0 |url=}}</ref><ref name="pmid3028640">{{cite journal |vauthors=Hynes RO |title=Integrins: a family of cell surface receptors |journal=Cell |volume=48 |issue=4 |pages=549–54 |date=February 1987 |pmid=3028640 |doi= |url=}}</ref><ref name="pmid1538783">{{cite journal |vauthors=Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N |title=Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin |journal=Nature |volume=356 |issue=6364 |pages=63–6 |date=March 1992 |pmid=1538783 |doi=10.1038/356063a0 |url=}}</ref><ref name="pmid7730443">{{cite journal |vauthors=Kent SJ, Karlik SJ, Cannon C, Hines DK, Yednock TA, Fritz LC, Horner HC |title=A monoclonal antibody to alpha 4 integrin suppresses and reverses active experimental allergic encephalomyelitis |journal=J. Neuroimmunol. |volume=58 |issue=1 |pages=1–10 |date=April 1995 |pmid=7730443 |doi= |url=}}</ref>
* [[Natalizumab|Natalizumab]]: This [[drug]] works as an [[antibody]] against alpha 4 subunit of [[integrin]]. As a result of [[Blood brain barrier]] disruption, [[inflammatory cells]] like [[Lymphocyte|lymphocytes]] and [[Monocyte|monocytes]] can access the [[Brain tissue|brain parenchyma]] and start the process of [[inflammation]] and destruction. [[Integrin]] 4 is on the surface of these [[inflammatory cells]] and helps their adhesion to [[vascular]] [[endothelium]]. Based on some studies using this drug can reduce [[signs]], [[Symptom|symptoms]] and [[Relapse|relapses]] of the [[disease]].<ref name="pmid15851719">{{cite journal |vauthors=Rice GP, Hartung HP, Calabresi PA |title=Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale |journal=Neurology |volume=64 |issue=8 |pages=1336–42 |date=April 2005 |pmid=15851719 |doi=10.1212/01.WNL.0000158329.30470.D0 |url=}}</ref><ref name="pmid3028640">{{cite journal |vauthors=Hynes RO |title=Integrins: a family of cell surface receptors |journal=Cell |volume=48 |issue=4 |pages=549–54 |date=February 1987 |pmid=3028640 |doi= |url=}}</ref><ref name="pmid1538783">{{cite journal |vauthors=Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N |title=Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin |journal=Nature |volume=356 |issue=6364 |pages=63–6 |date=March 1992 |pmid=1538783 |doi=10.1038/356063a0 |url=}}</ref><ref name="pmid7730443">{{cite journal |vauthors=Kent SJ, Karlik SJ, Cannon C, Hines DK, Yednock TA, Fritz LC, Horner HC |title=A monoclonal antibody to alpha 4 integrin suppresses and reverses active experimental allergic encephalomyelitis |journal=J. Neuroimmunol. |volume=58 |issue=1 |pages=1–10 |date=April 1995 |pmid=7730443 |doi= |url=}}</ref>


* '''[[Alemtuzumab]]:''' This [[drug]] is a [[monoclonal antibody]] and can cause reduction in [[CD52]]-expressing [[T cells]], [[B cells]], [[Natural killer cell|natural killer cells]] and [[monocytes]]. The [[side effects]] of this [[drug]] includes: [[infection]], [[autoimmune disorders]] and [[Infusion reactions|infusion reaction]].<ref name="pmid26204829">{{cite journal |vauthors=Ruck T, Bittner S, Wiendl H, Meuth SG |title=Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond |journal=Int J Mol Sci |volume=16 |issue=7 |pages=16414–39 |date=July 2015 |pmid=26204829 |pmc=4519957 |doi=10.3390/ijms160716414 |url=}}</ref><ref name="pmid18946064">{{cite journal |vauthors=Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK |title=Alemtuzumab vs. interferon beta-1a in early multiple sclerosis |journal=N. Engl. J. Med. |volume=359 |issue=17 |pages=1786–801 |date=October 2008 |pmid=18946064 |doi=10.1056/NEJMoa0802670 |url=}}</ref><ref name="pmid23122652">{{cite journal |vauthors=Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA |title=Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial |journal=Lancet |volume=380 |issue=9856 |pages=1819–28 |date=November 2012 |pmid=23122652 |doi=10.1016/S0140-6736(12)61769-3 |url=}}</ref>
* [[Alemtuzumab]]: This [[drug]] is a [[monoclonal antibody]] and can cause reduction in [[CD52]]-expressing [[T cells]], [[B cells]], [[Natural killer cell|natural killer cells]] and [[monocytes]]. The [[side effects]] of this [[drug]] includes: [[infection]], [[autoimmune disorders]] and [[Infusion reactions|infusion reaction]].<ref name="pmid26204829">{{cite journal |vauthors=Ruck T, Bittner S, Wiendl H, Meuth SG |title=Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond |journal=Int J Mol Sci |volume=16 |issue=7 |pages=16414–39 |date=July 2015 |pmid=26204829 |pmc=4519957 |doi=10.3390/ijms160716414 |url=}}</ref><ref name="pmid18946064">{{cite journal |vauthors=Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK |title=Alemtuzumab vs. interferon beta-1a in early multiple sclerosis |journal=N. Engl. J. Med. |volume=359 |issue=17 |pages=1786–801 |date=October 2008 |pmid=18946064 |doi=10.1056/NEJMoa0802670 |url=}}</ref><ref name="pmid23122652">{{cite journal |vauthors=Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA |title=Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial |journal=Lancet |volume=380 |issue=9856 |pages=1819–28 |date=November 2012 |pmid=23122652 |doi=10.1016/S0140-6736(12)61769-3 |url=}}</ref>


* '''[[Ocrelizumab]]:''' [[Ocrelizumab]] is a [[monoclonal antibody]] against [[CD20]] causing [[B cells]] depletion.<ref name="pmid28002679">{{cite journal |vauthors=Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L |title=Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis |journal=N. Engl. J. Med. |volume=376 |issue=3 |pages=221–234 |date=January 2017 |pmid=28002679 |doi=10.1056/NEJMoa1601277 |url=}}</ref> It can reduce gadolinium-enhancing [[brain]] [[lesions]] on [[MRI]] of [[MS]] patients.<ref name="pmid22047971">{{cite journal |vauthors=Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A, Barkhof F, Yin M, Leppert D, Glanzman R, Tinbergen J, Hauser SL |title=Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial |journal=Lancet |volume=378 |issue=9805 |pages=1779–87 |date=November 2011 |pmid=22047971 |doi=10.1016/S0140-6736(11)61649-8 |url=}}</ref>
* [[Ocrelizumab]]: [[Ocrelizumab]] is a [[monoclonal antibody]] against [[CD20]] causing [[B cells]] depletion.<ref name="pmid28002679">{{cite journal |vauthors=Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L |title=Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis |journal=N. Engl. J. Med. |volume=376 |issue=3 |pages=221–234 |date=January 2017 |pmid=28002679 |doi=10.1056/NEJMoa1601277 |url=}}</ref> It can reduce [[gadolinium]]-enhancing [[brain]] [[lesions]] on [[MRI]] of [[MS]] patients.<ref name="pmid22047971">{{cite journal |vauthors=Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A, Barkhof F, Yin M, Leppert D, Glanzman R, Tinbergen J, Hauser SL |title=Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial |journal=Lancet |volume=378 |issue=9805 |pages=1779–87 |date=November 2011 |pmid=22047971 |doi=10.1016/S0140-6736(11)61649-8 |url=}}</ref>


* '''[[Mitoxantrone]]:''' This [[drug]] has some serious [[side effects]] including [[cardiac]] [[toxicity]], so it’s more like a reserve [[drug]] for [[patients]] who don’t respond to other therapies.
* [[Mitoxantrone]]: This [[drug]] has serious [[side effects]] including [[cardiac]] [[toxicity]], so it’s more like a reserve [[drug]] for [[patients]] who don’t respond to other therapies.<ref name="pmid14638950">{{cite journal |vauthors=Goodin DS, Arnason BG, Coyle PK, Frohman EM, Paty DW |title=The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology |journal=Neurology |volume=61 |issue=10 |pages=1332–8 |date=November 2003 |pmid=14638950 |doi= |url=}}</ref>


=== Management of Acute Attacks ===
==== Injectable therapies: ====
* [[Interferons]]: 1. [[Interferon beta-1b]]: This [[drug]] is a [[cytokine]] that can affect [[immune system]] and modulates it and cause reduction in the [[progression]] of the [[disease]].<ref name="pmid25356432">{{cite journal |vauthors=Kasper LH, Reder AT |title=Immunomodulatory activity of interferon-beta |journal=Ann Clin Transl Neurol |volume=1 |issue=8 |pages=622–31 |date=August 2014 |pmid=25356432 |pmc=4184564 |doi=10.1002/acn3.84 |url=}}</ref><ref name="pmid7617182">{{cite journal |vauthors= |title=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 |journal=Neurology |volume=45 |issue=7 |pages=1277–85 |date=July 1995 |pmid=7617182 |doi= |url=}}</ref> 2.  [[Interferon beta-1a]]: Both [[Intramuscular]] and [[Subcutaneous]] [[interferon beta-1a]] can reduce disease progression, [[MRI]] [[Lesions of the anterior vermis of the cerebellum|lesions]] and [[acute]] attacks.<ref name="pmid9820297">{{cite journal |vauthors= |title=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 |journal=Lancet |volume=352 |issue=9139 |pages=1498–504 |date=November 1998 |pmid=9820297 |doi= |url=}}</ref><ref name="pmid12451189">{{cite journal |vauthors=Clanet M, Radue EW, Kappos L, Hartung HP, Hohlfeld R, Sandberg-Wollheim M, Kooijmans-Coutinho MF, Tsao EC, Sandrock AW |title=A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS |journal=Neurology |volume=59 |issue=10 |pages=1507–17 |date=November 2002 |pmid=12451189 |doi= |url=}}</ref>
* [[Glatiramer]]: [[Glatiramer]] is made from four [[amino acids]] and structurally similar to [[myelin basic protein]]. It binds to [[Major histocompatibility complex|major histocompatibility complex molecules]] and competes with [[myelin]] antigens for [[T cell]] presentation.<ref name="pmid15371592">{{cite journal |vauthors=Arnon R, Aharoni R |title=Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 Suppl 2 |issue= |pages=14593–8 |date=October 2004 |pmid=15371592 |pmc=521994 |doi=10.1073/pnas.0404887101 |url=}}</ref> this drug can reduce [[relapse]] rate of the disease.<ref name="pmid7617181">{{cite journal |vauthors=Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB |title=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 |journal=Neurology |volume=45 |issue=7 |pages=1268–76 |date=July 1995 |pmid=7617181 |doi= |url=}}</ref>
* [[Daclizumab]]: It is a [[monoclonal antibody]] against alpha chain of [[interleukin 2]] receptor. It can reduce the [[relapses]] in [[MS]] patients.<ref name="pmid23562009">{{cite journal |vauthors=Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, Robinson R, Riester K, Rana J, Elkins J, O'Neill G |title=Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial |journal=Lancet |volume=381 |issue=9884 |pages=2167–75 |date=June 2013 |pmid=23562009 |doi=10.1016/S0140-6736(12)62190-4 |url=}}</ref>


During symptomatic attacks administration of high doses of [[intravenous therapy|intravenous]] [[corticosteroid]]s, such as [[methylprednisolone]],<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682795.html Methylprednisolone Oral.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on[[2007-09-01]].</ref><ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601157.html Methylprednisolone Sodium Succinate Injection.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-09-01]].</ref> is the routine therapy for acute relapses.The aim of this kind of treatment is to end the attack sooner and leave fewer lasting deficits in the patient. Although generally effective in the short term for relieving [[symptom]]s, corticosteroid treatments do not appear to have a significant impact on long-term recovery.<ref>{{cite journal |author=Brusaferri F, Candelise L |title=Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials |journal=J. Neurol. |volume=247 |issue=6|pages=435–42 |year=2000 |pmid=10929272 |doi=}}</ref> Potential side effects include osteoporosis<ref>{{cite journal |author=Dovio A, Perazzolo L, Osella G, ''et al'' |title=Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis |journal=J. Clin. Endocrinol. Metab.|volume=89 |issue=10 |pages=4923–8 |year=2004 |pmid=15472186 |doi=10.1210/jc.2004-0164}}</ref> and impaired memory, being the latter reversible<ref>{{cite journal |author=Uttner I, Müller S, Zinser C, ''et al'' |title=Reversible impaired memory induced by pulsed methylprednisolone in patients with MS |journal=Neurology |volume=64 |issue=11 |pages=1971–3 |year=2005 |pmid=15955958|doi=10.1212/01.WNL.0000163804.94163.91}}</ref>
==== Oral therapies: ====
* [[Dimethyl fumarate]]: Fumarates is a [[neuroprotective]] and [[Immunomodulator|immunomodulatory]] drug which can reduce [[acute]] attacks and [[progression]] of multiple sclerosis.<ref name="pmid22992072">{{cite journal |vauthors=Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT |title=Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis |journal=N. Engl. J. Med. |volume=367 |issue=12 |pages=1087–97 |date=September 2012 |pmid=22992072 |doi=10.1056/NEJMoa1206328 |url=}}</ref><ref name="pmid22992073">{{cite journal |vauthors=Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT |title=Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis |journal=N. Engl. J. Med. |volume=367 |issue=12 |pages=1098–107 |date=September 2012 |pmid=22992073 |doi=10.1056/NEJMoa1114287 |url=}}</ref><ref name="pmid25900414">{{cite journal |vauthors=Xu Z, Zhang F, Sun F, Gu K, Dong S, He D |title=Dimethyl fumarate for multiple sclerosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD011076 |date=April 2015 |pmid=25900414 |doi=10.1002/14651858.CD011076.pub2 |url=}}</ref>


Medical management of few individual symptoms and/or signs is as follows :-
* [[Teriflunomide]]: This [[drug]] inhibits the [[biosynthesis]] of [[pyrimidines]] and reduces the interaction between [[antigen presenting cells]] and [[T cells]].<ref name="pmid16142756">{{cite journal |vauthors=Zeyda M, Poglitsch M, Geyeregger R, Smolen JS, Zlabinger GJ, Hörl WH, Waldhäusl W, Stulnig TM, Säemann MD |title=Disruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formation |journal=Arthritis Rheum. |volume=52 |issue=9 |pages=2730–9 |date=September 2005 |pmid=16142756 |doi=10.1002/art.21255 |url=}}</ref> [[teriflunomide]] can reduce [[relapse]] rate and [[disability]] [[progression]] of [[MS]] disease.<ref name="pmid21991951">{{cite journal |vauthors=O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS |title=Randomized trial of oral teriflunomide for relapsing multiple sclerosis |journal=N. Engl. J. Med. |volume=365 |issue=14 |pages=1293–303 |date=October 2011 |pmid=21991951 |doi=10.1056/NEJMoa1014656 |url=}}</ref><ref name="pmid27003123">{{cite journal |vauthors=He D, Zhang C, Zhao X, Zhang Y, Dai Q, Li Y, Chu L |title=Teriflunomide for multiple sclerosis |journal=Cochrane Database Syst Rev |volume=3 |issue= |pages=CD009882 |date=March 2016 |pmid=27003123 |doi=10.1002/14651858.CD009882.pub3 |url=}}</ref> The most common [[side effects]] of this [[drug]] are [[nausea]], [[diarrhea]] and elevated [[aminotransferase]] level.<ref name="pmid21991951">{{cite journal |vauthors=O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS |title=Randomized trial of oral teriflunomide for relapsing multiple sclerosis |journal=N. Engl. J. Med. |volume=365 |issue=14 |pages=1293–303 |date=October 2011 |pmid=21991951 |doi=10.1056/NEJMoa1014656 |url=}}</ref><ref name="pmid16567708">{{cite journal |vauthors=O'Connor PW, Li D, Freedman MS, Bar-Or A, Rice GP, Confavreux C, Paty DW, Stewart JA, Scheyer R |title=A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses |journal=Neurology |volume=66 |issue=6 |pages=894–900 |date=March 2006 |pmid=16567708 |doi=10.1212/01.wnl.0000203121.04509.31 |url=}}</ref><ref name="pmid26865517">{{cite journal |vauthors=O'Connor P, Comi G, Freedman MS, Miller AE, Kappos L, Bouchard JP, Lebrun-Frenay C, Mares J, Benamor M, Thangavelu K, Liang J, Truffinet P, Lawson VJ, Wolinsky JS |title=Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study |journal=Neurology |volume=86 |issue=10 |pages=920–30 |date=March 2016 |pmid=26865517 |pmc=4782117 |doi=10.1212/WNL.0000000000002441 |url=}}</ref>
* [[Fingolimod]]: [[Fingolimod]] is an [[Analog (chemistry)|analog]] of [[sphingosine]] and can reduce [[lymphocyte]] migration and acute relapses of the disease.<ref name="pmid21520239">{{cite journal |vauthors=Cohen JA, Chun J |title=Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis |journal=Ann. Neurol. |volume=69 |issue=5 |pages=759–77 |date=May 2011 |pmid=21520239 |doi=10.1002/ana.22426 |url=}}</ref><ref name="pmid27091121">{{cite journal |vauthors=La Mantia L, Tramacere I, Firwana B, Pacchetti I, Palumbo R, Filippini G |title=Fingolimod for relapsing-remitting multiple sclerosis |journal=Cochrane Database Syst Rev |volume=4 |issue= |pages=CD009371 |date=April 2016 |pmid=27091121 |doi=10.1002/14651858.CD009371.pub2 |url=}}</ref>


===Bladder===
=== Treatment of progressive multiple sclerosis ===
Treatment objectives are alleviation of symptoms of urinary dysfunction, treatment of urinary infections, reduction of complicating factors and preservation of [[kidney|renal]] function. Treatments can be classified in two main subtypes: pharmacological and non pharmacological.
* Studies show that [[Immunosuppression|immunosuppressive threpay]] includes Total [[lymphoid]] irradiation, [[Cyclosporine|cyclosporin]], [[Methotrexate]], [[Cladribine]], [[Cyclophosphamide]], [[Mitoxantrone]], [[Azathioprine]], [[Interferon]], [[Corticosteroid]], [[Intravenous immunoglobulin]], [[Plasma]] exchange, [[bone marrow transplant]], [[Natalizumab|Anti-integrin antibodies]] ([[natalizumab]]) can be beneficial in progressive and sever case of multiple sclerosis.<ref name="pmid65452">{{cite journal |vauthors=Gonsette RE, Demonty L, Delmotte P |title=Intensive immunosuppression with cyclophosphamide in multiple sclerosis. Follow up of 110 patients for 2-6 years |journal=J. Neurol. |volume=214 |issue=3 |pages=173–81 |date=February 1977 |pmid=65452 |doi= |url=}}</ref><ref name="pmid6157011">{{cite journal |vauthors=Hommers OR, Lamers KJ, Reekers P |title=Effect of intensive immunosuppression on the course of chronic progressive multiple sclerosis |journal=J. Neurol. |volume=223 |issue=3 |pages=177–90 |date=1980 |pmid=6157011 |doi= |url=}}</ref><ref name="pmid6124759">{{cite journal |vauthors=Mertin J, Rudge P, Kremer M, Healey MJ, Knight SC, Compston A, Batchelor JR, Thompson EJ, Halliday AM, Denman M, Medawar PB |title=Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report |journal=Lancet |volume=2 |issue=8294 |pages=351–4 |date=August 1982 |pmid=6124759 |doi= |url=}}</ref><ref name="pmid2872516">{{cite journal |vauthors=Cook SD, Devereux C, Troiano R, Hafstein MP, Zito G, Hernandez E, Lavenhar M, Vidaver R, Dowling PC |title=Effect of total lymphoid irradiation in chronic progressive multiple sclerosis |journal=Lancet |volume=1 |issue=8495 |pages=1405–9 |date=June 1986 |pmid=2872516 |doi= |url=}}</ref><ref name="pmid2193613">{{cite journal |vauthors= |title=Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group |journal=Ann. Neurol. |volume=27 |issue=6 |pages=591–605 |date=June 1990 |pmid=2193613 |doi=10.1002/ana.410270603 |url=}}</ref><ref name="pmid7818255">{{cite journal |vauthors=Goodkin DE, Rudick RA, VanderBrug Medendorp S, Daughtry MM, Schwetz KM, Fischer J, Van Dyke C |title=Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis |journal=Ann. Neurol. |volume=37 |issue=1 |pages=30–40 |date=January 1995 |pmid=7818255 |doi=10.1002/ana.410370108 |url=}}</ref><ref name="pmid7912347">{{cite journal |vauthors=Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J, Beutler E |title=Cladribine in treatment of chronic progressive multiple sclerosis |journal=Lancet |volume=344 |issue=8914 |pages=9–13 |date=July 1994 |pmid=7912347 |doi= |url=}}</ref><ref name="pmid6294517">{{cite journal |vauthors=Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, Mills JA, Weiner HL |title=Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH |journal=N. Engl. J. Med. |volume=308 |issue=4 |pages=173–80 |date=January 1983 |pmid=6294517 |doi=10.1056/NEJM198301273080401 |url=}}</ref><ref name="pmid9048709">{{cite journal |vauthors=Edan G, Miller D, Clanet M, Confavreux C, Lyon-Caen O, Lubetzki C, Brochet B, Berry I, Rolland Y, Froment JC, Cabanis E, Iba-Zizen MT, Gandon JM, Lai HM, Moseley I, Sabouraud O |title=Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria |journal=J. Neurol. Neurosurg. Psychiatry |volume=62 |issue=2 |pages=112–8 |date=February 1997 |pmid=9048709 |pmc=486720 |doi= |url=}}</ref><ref name="pmid1681364">{{cite journal |vauthors=Yudkin PL, Ellison GW, Ghezzi A, Goodkin DE, Hughes RA, McPherson K, Mertin J, Milanese C |title=Overview of azathioprine treatment in multiple sclerosis |journal=Lancet |volume=338 |issue=8774 |pages=1051–5 |date=October 1991 |pmid=1681364 |doi= |url=}}</ref><ref name="pmid9820296">{{cite journal |vauthors= |title=Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS |journal=Lancet |volume=352 |issue=9139 |pages=1491–7 |date=November 1998 |pmid=9820296 |doi= |url=}}</ref><ref name="pmid9674809">{{cite journal |vauthors=Goodkin DE, Kinkel RP, Weinstock-Guttman B, VanderBrug-Medendorp S, Secic M, Gogol D, Perryman JE, Uccelli MM, Neilley L |title=A phase II study of i.v. methylprednisolone in secondary-progressive multiple sclerosis |journal=Neurology |volume=51 |issue=1 |pages=239–45 |date=July 1998 |pmid=9674809 |doi= |url=}}</ref><ref name="pmid9057729">{{cite journal |vauthors=Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B |title=Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group |journal=Lancet |volume=349 |issue=9052 |pages=589–93 |date=March 1997 |pmid=9057729 |doi= |url=}}</ref><ref name="pmid10589540">{{cite journal |vauthors=Weinshenker BG, O'Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW, Pineda AA, Stevens LN, Rodriguez M |title=A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease |journal=Ann. Neurol. |volume=46 |issue=6 |pages=878–86 |date=December 1999 |pmid=10589540 |doi= |url=}}</ref><ref name="pmid8467289">{{cite journal |vauthors=van Gelder M, Kinwel-Bohré EP, van Bekkum DW |title=Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT |journal=Bone Marrow Transplant. |volume=11 |issue=3 |pages=233–41 |date=March 1993 |pmid=8467289 |doi= |url=}}</ref><ref name="pmid1538783" />


Pharmacological treatments vary greatly depending on the origin or type of dysfunction; however some examples of the medications used are:<ref>{{cite journal |author=Ayuso-Peralta L, de Andrés C |title=[Symptomatic treatment of multiple sclerosis]|language=Spanish; Castilian |journal=Revista de neurologia |volume=35 |issue=12 |pages=1141-53 |year=2002 |pmid=12497297|doi=}}</ref>
=== Treatment of acute exacerbation of multiple sclerosis ===
[[alfuzosin]] for retention,<ref>Information from the USA National library of medicine on alfuzosin[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a604002.html]</ref>
* Management of acute attacks of multiple sclerosis may help patients to recover faster but has no effect in long term [[signs]] and [[symptoms]].<ref name="pmid10929272">{{cite journal |vauthors=Brusaferri F, Candelise L |title=Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials |journal=J. Neurol. |volume=247 |issue=6 |pages=435–42 |date=June 2000 |pmid=10929272 |doi= |url=}}</ref><ref name="pmid14663037">{{cite journal |vauthors=Lublin FD, Baier M, Cutter G |title=Effect of relapses on development of residual deficit in multiple sclerosis |journal=Neurology |volume=61 |issue=11 |pages=1528–32 |date=December 2003 |pmid=14663037 |doi= |url=}}</ref>
[[trospium]] and [[flavoxate]] for urgency and incontinency,<ref>Information from the USA National library of medicine on trospium[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a604037.html]</ref><ref>Information from the USA National library of medicine on flavoxate [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682706.html] </ref>
* [[Glucocorticoid]] therapy: We commonly use 500 to 1000 mg of [[methylprednisolone]] daily.<ref name="pmid8290041">{{cite journal |vauthors=Kupersmith MJ, Kaufman D, Paty DW, Ebers G, McFarland H, Johnson K, Reingold S, Whitaker J |title=Megadose corticosteroids in multiple sclerosis |journal=Neurology |volume=44 |issue=1 |pages=1–4 |date=January 1994 |pmid=8290041 |doi= |url=}}</ref>  
or [[desmopressin]] for [[nocturia]].<ref>{{cite journal |author=Bosma R, Wynia K, Havlíková E, De Keyser J, Middel B|title=Efficacy of desmopressin in patients with multiple sclerosis suffering from bladder dysfunction: a meta-analysis|journal=Acta Neurol. Scand. |volume=112 |issue=1 |pages=1-5 |year=2005 |pmid=15932348|doi=10.1111/j.1600-0404.2005.00431.x}}</ref><ref>Information from the USA National library of medicine on desmopressin[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682876.html]</ref>
* The [[side effects]] of this [[therapy]] include [[depression]] or [[mania]], [[infection]] and [[Gastrointestinal tract|GI]] disturbance.<ref name="pmid26334182">{{cite journal |vauthors=Morrow SA, Barr J, Rosehart H, Ulch S |title=Depression and hypomania symptoms are associated with high dose corticosteroids treatment for MS relapses |journal=J Affect Disord |volume=187 |issue= |pages=142–6 |date=November 2015 |pmid=26334182 |doi=10.1016/j.jad.2015.08.040 |url=}}</ref>  
* Multiple studies demonstrate that [[plasma]] exchange can be beneficial in acute attacks of multiple sclerosis too.<ref name="pmid10589540">{{cite journal |vauthors=Weinshenker BG, O'Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW, Pineda AA, Stevens LN, Rodriguez M |title=A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease |journal=Ann. Neurol. |volume=46 |issue=6 |pages=878–86 |date=December 1999 |pmid=10589540 |doi= |url=}}</ref><ref name="pmid26244762">{{cite journal |vauthors=Ehler J, Koball S, Sauer M, Mitzner S, Hickstein H, Benecke R, Zettl UK |title=Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients |journal=PLoS ONE |volume=10 |issue=8 |pages=e0134583 |date=2015 |pmid=26244762 |pmc=4526633 |doi=10.1371/journal.pone.0134583 |url=}}</ref>


Non pharmacological treatments involve the use of [[pelvic floor]] muscle training, stimulation [[biofeedback]], [[pessary|pessaries]], bladder training, and sometimes intermittent [[urinary catheterization|catheterization]].<ref>Frances M Diro (2006) "Urological Management in Neurological Disease". [http://www.emedicine.com/neuro/topic673.htm]</ref>
=== Symptom management ===
* Bladder dysfunction: [[Bladder]] dysfunction due to detresor overactivity can be treated with [[antimuscarinic]] and [[anticholinergic]] drugs such as [[oxybutynin]], [[tolterodine]], [[propantheline]], [[propiverine]], [[fesoterodine]], and [[solifenacin]].<ref name="pmid24314685">{{cite journal |vauthors=Yang CC |title=Bladder management in multiple sclerosis |journal=Phys Med Rehabil Clin N Am |volume=24 |issue=4 |pages=673–86 |date=November 2013 |pmid=24314685 |doi=10.1016/j.pmr.2013.06.004 |url=}}</ref><ref name="pmid21694806">{{cite journal |vauthors=Frohman TC, Castro W, Shah A, Courtney A, Ortstadt J, Davis SL, Logan D, Abraham T, Abraham J, Remington G, Treadaway K, Graves D, Hart J, Stuve O, Lemack G, Greenberg B, Frohman EM |title=Symptomatic therapy in multiple sclerosis |journal=Ther Adv Neurol Disord |volume=4 |issue=2 |pages=83–98 |date=March 2011 |pmid=21694806 |pmc=3105617 |doi=10.1177/1756285611400658 |url=}}</ref>


===Cognition===
* [[Sexual dysfunction]]: The very first step in treating [[sexual dysfunction]] is to treat [[Neuropathic pain|neuropathic]] or [[visual]] [[pain]] and [[spasticity]]. These are the main causes of [[sexual dysfunction]]. [[Phosphodiesterase-5 inhibitor|Phosphodiesterase-5 inhibitors]] can be very helpful in men with [[MS]] who have [[erectile dysfunction]].<ref name="pmid10022678">{{cite journal |vauthors=Litwiller SE, Frohman EM, Zimmern PE |title=Multiple sclerosis and the urologist |journal=J. Urol. |volume=161 |issue=3 |pages=743–57 |date=March 1999 |pmid=10022678 |doi= |url=}}</ref><ref name="pmid15834030">{{cite journal |vauthors=Fowler CJ, Miller JR, Sharief MK, Hussain IF, Stecher VJ, Sweeney M |title=A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis |journal=J. Neurol. Neurosurg. Psychiatry |volume=76 |issue=5 |pages=700–5 |date=May 2005 |pmid=15834030 |pmc=1739638 |doi=10.1136/jnnp.2004.038695 |url=}}</ref><ref name="pmid19013598">{{cite journal |vauthors=Safarinejad MR |title=Evaluation of the safety and efficacy of sildenafil citrate for erectile dysfunction in men with multiple sclerosis: a double-blind, placebo controlled, randomized study |journal=J. Urol. |volume=181 |issue=1 |pages=252–8 |date=January 2009 |pmid=19013598 |doi=10.1016/j.juro.2008.09.003 |url=}}</ref>


Interferons have demonstrated that can help to reduce cognitive limitations in multiple sclerosis.<ref>{{cite journal |author=Montalban X, Rio J|title=Interferons and cognition |journal=J Neurol Sci |volume=245 |issue=1-2 |pages=137-40 |year=2006 |pmid=16626757}}</ref>[[Anticholinesterase]] drugs such as [[donepezil]] commonly used in [[alzheimer disease]]; although not approved yet for multiple sclerosis; have also shown efficacy in different clinical trials.<ref>{{cite journal |author=Christodoulou C, Melville P, Scherl W, Macallister W, Elkins L, Krupp L |title=Effects of donepezil on memory and cognition in multiple sclerosis |journal=J Neurol Sci|volume=245 |issue=1-2 |pages=127-36 |year=2006 |pmid=16626752}}</ref><ref>{{cite journal |author=Porcel J, Montalban X|title=Anticholinesterasics in the treatment of cognitive impairment in multiple sclerosis |journal=J Neurol Sci |volume=245|issue=1-2 |pages=177-81 |year=2006 |pmid=16674980}}</ref><ref>Information from the USA National library of medicine on donepezil[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a697032.html]</ref>
* [[Cognition]]: Some of disease modifying treatments such as [[interferons]], [[natalizumab]], and [[fingolimod]] seems to have a good effect on [[cognitive]] problems in [[MS]] patients. There is some evidence of the [[cholinesterase inhibitors]] ([[donepezil]]) being beneficial to [[MS]] patients with [[Cognitive disorder|cognitive disorders]].<ref name="pmid22876911">{{cite journal |vauthors=Patti F |title=Treatment of cognitive impairment in patients with multiple sclerosis |journal=Expert Opin Investig Drugs |volume=21 |issue=11 |pages=1679–99 |date=November 2012 |pmid=22876911 |doi=10.1517/13543784.2012.716036 |url=}}</ref><ref name="pmid15534239">{{cite journal |vauthors=Krupp LB, Christodoulou C, Melville P, Scherl WF, MacAllister WS, Elkins LE |title=Donepezil improved memory in multiple sclerosis in a randomized clinical trial |journal=Neurology |volume=63 |issue=9 |pages=1579–85 |date=November 2004 |pmid=15534239 |doi= |url=}}</ref>


===Fatigue===
* Fatigue: [[Drugs]] such as [[amantadine]]<ref name="pmid17253480">{{cite journal |author=Pucci E, Branãs P, D'Amico R, Giuliani G, Solari A, Taus C|title=Amantadine for fatigue in multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1|pages=CD002818 |year=2007 |pmid=17253480 |doi=10.1002/14651858.CD002818.pub2}}</ref><ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682064.html Amantadine.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-10-07]].</ref>and [[pemoline]] <ref name="pmid1641137">{{cite journal |author=Weinshenker BG, Penman M, Bass B, Ebers GC, Rice GP |title=A double-blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis |journal=Neurology |volume=42 |issue=8 |pages=1468–71 |year=1992 |pmid=1641137 |doi=}}</ref><ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682313.html Pemoline.] US National Library of Medicine (Medline) ([[2006-01-01]]). Retrieved on [[2007-10-07]].</ref> as well as [[psychological]] consult <ref name="pmid16193899">{{cite journal |author=Mathiowetz VG, Finlayson ML, Matuska KM, Chen HY, Luo P |title=Randomized controlled trial of an energy conservation course for persons with multiple sclerosis |journal=Mult. Scler. |volume=11 |issue=5 |pages=592–601|year=2005 |pmid=16193899 |doi=}}</ref><ref name="pmid17302106">{{cite journal |author=Matuska K, Mathiowetz V, Finlayson M|title=Use and perceived effectiveness of energy conservation strategies for managing multiple sclerosis fatigue |journal=The American journal of occupational therapy. : official publication of the American Occupational Therapy Association |volume=61|issue=1 |pages=62–9 |year=2007 |pmid=17302106 |doi=}}</ref> can have a good effect on reducing [[fatigue]] in [[MS]] patients.


There are also different medications used to treat fatigue; such as [[amantadine]],<ref name="pmid17253480">{{cite journal |author=Pucci E, Branãs P, D'Amico R, Giuliani G, Solari A, Taus C|title=Amantadine for fatigue in multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1|pages=CD002818 |year=2007 |pmid=17253480 |doi=10.1002/14651858.CD002818.pub2}}</ref><ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682064.html Amantadine.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-10-07]].</ref> or [[pemoline]] <ref name="pmid1641137">{{cite journal |author=Weinshenker BG, Penman M, Bass B, Ebers GC, Rice GP |title=A double-blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis |journal=Neurology |volume=42 |issue=8 |pages=1468–71 |year=1992 |pmid=1641137 |doi=}}</ref><ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682313.html Pemoline.] US National Library of Medicine (Medline) ([[2006-01-01]]). Retrieved on [[2007-10-07]].</ref> as well as psychological interventions of energy conservation;<ref name="pmid16193899">{{cite journal |author=Mathiowetz VG, Finlayson ML, Matuska KM, Chen HY, Luo P |title=Randomized controlled trial of an energy conservation course for persons with multiple sclerosis |journal=Mult. Scler. |volume=11 |issue=5 |pages=592–601|year=2005 |pmid=16193899 |doi=}}</ref><ref name="pmid17302106">{{cite journal |author=Matuska K, Mathiowetz V, Finlayson M|title=Use and perceived effectiveness of energy conservation strategies for managing multiple sclerosis fatigue |journal=The American journal of occupational therapy. : official publication of the American Occupational Therapy Association |volume=61|issue=1 |pages=62–9 |year=2007 |pmid=17302106 |doi=}}</ref> but the effects of all of them are small. For this reason fatigue is a very difficult symptom to manage.
* [[Internuclear ophthalmoplegia]]: Potassium channel blocker, like [[dalfampridine]], can have a good effect on [[axonal]] function and improving acular [[adduction]].<ref name="pmid24907233">{{cite journal |vauthors=Serra A, Skelly MM, Jacobs JB, Walker MF, Cohen JA |title=Improvement of internuclear ophthalmoparesis in multiple sclerosis with dalfampridine |journal=Neurology |volume=83 |issue=2 |pages=192–4 |date=July 2014 |pmid=24907233 |pmc=4117173 |doi=10.1212/WNL.0000000000000567 |url=}}</ref> [[Botulinum]] injection into eye muscles can improve [[diplopia]] in some patients.<ref name="pmid17498988">{{cite journal |vauthors=Murthy R, Dawson E, Khan S, Adams GG, Lee J |title=Botulinum toxin in the management of internuclear ophthalmoplegia |journal=J AAPOS |volume=11 |issue=5 |pages=456–9 |date=October 2007 |pmid=17498988 |doi=10.1016/j.jaapos.2007.03.005 |url=}}</ref><ref name="pmid28819801">{{cite journal |vauthors=Safarpour Y, Mousavi T, Jabbari B |title=Botulinum Toxin Treatment in Multiple Sclerosis-a Review |journal=Curr Treat Options Neurol |volume=19 |issue=10 |pages=33 |date=August 2017 |pmid=28819801 |doi=10.1007/s11940-017-0470-5 |url=}}</ref>


===Internuclear Ophthalmoplegia===
* Optic Neuritis: [[Intravenous]] treatment with [[methylprednisolon]] may have beneficial effect on [[visual]] function.<ref name="pmid10227638">{{cite journal |vauthors=Sellebjerg F, Nielsen HS, Frederiksen JL, Olesen J |title=A randomized, controlled trial of oral high-dose methylprednisolone in acute optic neuritis |journal=Neurology |volume=52 |issue=7 |pages=1479–84 |date=April 1999 |pmid=10227638 |doi= |url=}}</ref>


Different drugs as well as optic compensatory systems and prisms can be used to improve this symptoms.<ref>{{cite journal|author=Leigh RJ, Averbuch-Heller L, Tomsak RL, Remler BF, Yaniglos SS, Dell'Osso LF |title=Treatment of abnormal eye movements that impair vision: strategies based on current concepts of physiology and pharmacology |journal=Ann. Neurol. |volume=36 |issue=2|pages=129-41 |year=1994 |pmid=8053648}}</ref><ref>{{cite journal |author=Starck M, Albrecht H, Pöllmann W, Straube A, Dieterich M|title=Drug therapy for acquired pendular nystagmus in multiple sclerosis |journal=J. Neurol. |volume=244 |issue=1 |pages=9-16|year=1997 |pmid=9007739}}</ref><ref>{{cite journal |author=Clanet MG, Brassat D |title=The management of multiple sclerosis patients |journal=Curr. Opin. Neurol. |volume=13 |issue=3 |pages=263-70 |year=2000 |pmid=10871249}}</ref><ref>{{cite journal|author=Menon GJ, Thaller VT |title=Therapeutic external ophthalmoplegia with bilateral retrobulbar botulinum toxin- an effective treatment for acquired nystagmus with oscillopsia |journal=Eye (London, England) |volume=16 |issue=6 |pages=804-6 |year=2002|pmid=12439689}}</ref>
* Trigeminal Neuralgia: Some [[drugs]] such as [[anticonvulsants]] ([[carbamazepine]]<ref>Information from the USA National library of medicine on carbamazepine[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682237.html]</ref>, [[phenytoin]]<ref>Information from the USA National library of medicine on phenytoin[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682022.html]</ref>, [[gabapentin]]<ref>Information from the USA National library of medicine on gabapentin[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a694007.html]</ref> <ref>{{cite journal |author=Solaro C, Messmer Uccelli M, Uccelli A, Leandri M, Mancardi GL |title=Low-dose gabapentin combined with either lamotrigine or carbamazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis |journal=Eur. Neurol.|volume=44 |issue=1 |pages=45-8 |year=2000 |pmid=10894995 |doi=}}</ref>) seems to be useful in treatment of [[trigeminal neuralgia]].
Surgery can also be used in some cases for this problem.<ref>{{cite journal |author=Jain S, Proudlock F, Constantinescu CS, Gottlob I |title=Combined pharmacologic and surgical approach to acquired nystagmus due to multiple sclerosis |journal=Am. J. Ophthalmol.|volume=134 |issue=5 |pages=780-2 |year=2002 |pmid=12429265}}</ref>


===Optic Neuritis===
* [[Lhermitte's sign|Lhermitte's Sign]] and [[Dysesthesias]]: These [[Symptom|symptoms]] can be treated with [[carbamazepine]], [[clonazepam]], and [[amitriptyline]].<ref>Information from the USA National library of medicine on clonazepam[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682279.html]</ref><ref>Information from the USA National library of medicine on amitriptyline[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682388.html]</ref><ref>{{cite journal|author=Moulin DE, Foley KM, Ebers GC |title=Pain syndromes in multiple sclerosis |journal=Neurology |volume=38 |issue=12|pages=1830-4 |year=1988 |pmid=2973568 |doi=}}</ref>


Systemic intravenous treatment with corticosteroids, which may quicken the healing of the optic nerve, prevent complete loss of vision, and delay the onset of other symptoms, is often recommended.
* [[Spasticity]]: Some drugs such as [[baclofen]]<ref>;[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682530.html Baclofen oral.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-10-17]].</ref>, [[dantrolene]]<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682576.html Dantrolene oral.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-10-17]].</ref>, [[diazepam]]<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682047.html Diazepam.] US National Library of Medicine (Medline) ([[2005-07-01]]). Retrieved on [[2007-10-17]].</ref>, [[tizanidine]]<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601121.html Tizanidine.] US National Library of Medicine (Medline) ([[2005-07-01]]). Retrieved on [[2007-10-17]].</ref><ref name="pmid14636486">{{cite journal |author=Beard S, Hunn A, Wight J|title=Treatments for spasticity and pain in multiple sclerosis: a systematic review |journal=Health technology assessment (Winchester, England) |volume=7 |issue=40 |pages=iii, ix–x, 1–111 |year=2003 |pmid=14636486 |doi=}}</ref><ref name="pmid12166503">{{cite journal |author=Paisley S, Beard S, Hunn A, Wight J |title=Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review |journal=Mult. Scler. |volume=8 |issue=4 |pages=319–29 |year=2002|pmid=12166503 |doi=}}</ref> and [[intrathecal]] injections of baclofen can be beneficial.<ref name="pmid8529173">{{cite journal |author=Becker WJ, Harris CJ, Long ML, Ablett DP, Klein GM, DeForge DA |title=Long-term intrathecal baclofen therapy in patients with intractable spasticity |journal=The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques |volume=22 |issue=3 |pages=208–17 |year=1995 |pmid=8529173 |doi=}}</ref>


===Trigeminal Neuralgia===
* Tremor and Ataxia: There are a list of drugs such as [[isoniazid]]<ref>{{cite journal |author=Bozek CB, Kastrukoff LF, Wright JM, Perry TL, Larsen TA |title=A controlled trial of isoniazid therapy for action tremor in multiple sclerosis |journal=J. Neurol. |volume=234 |issue=1|pages=36-9 |year=1987 |pmid=3546605 |doi=}}</ref><ref>{{cite journal |author=Duquette P, Pleines J, du Souich P |title=Isoniazid for tremor in multiple sclerosis: a controlled trial |journal=Neurology |volume=35 |issue=12 |pages=1772-5 |year=1985 |pmid=3906430|doi=}}</ref><ref>{{cite journal |author=Hallett M, Lindsey JW, Adelstein BD, Riley PO |title=Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis |journal=Neurology |volume=35 |issue=9 |pages=1374-7 |year=1985|pmid=3895037 |doi=}}</ref><ref>Information from the USA National library of medicine on Isoniazid
 
[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682401.html]</ref>, [[carbamazepine]]<ref>Information from the USA National library of medicine on carbamazepine [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682237.html]</ref>, [[propranolol]]<ref>{{cite journal |author=Koller WC |title=Pharmacologic trials in the treatment of cerebellar tremor|journal=Arch. Neurol. |volume=41 |issue=3 |pages=280-1 |year=1984 |pmid=6365047 |doi=}}</ref><ref>{{cite journal |author=Sechi GP, Zuddas M, Piredda M, Agnetti V, Sau G, Piras ML, Tanca S, Rosati G |title=Treatment of cerebellar tremors with carbamazepine: a controlled trial with long-term follow-up |journal=Neurology |volume=39 |issue=8 |pages=1113-5 |year=1989 |pmid=2668787|doi=}}</ref><ref>Information from the USA National library of medicine on propanolol[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682607.html]</ref> and gluthetimide,<ref>{{cite journal |author=Aisen ML, Holzer M, Rosen M, Dietz M, McDowell F |title=Glutethimide treatment of disabling action tremor in patients with multiple sclerosis and traumatic brain injury |journal=Arch. Neurol. |volume=48 |issue=5 |pages=513-5 |year=1991 |pmid=2021365 |doi=}}</ref> which we can use to reduce the [[tremor]] and [[ataxia]] in [[MS]] patients but their effectiveness is not considerable.<ref>{{cite journal |author=Mills RJ, Yap L, Young CA |title=Treatment for ataxia in multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD005029 |year=2007|pmid=17253537 |doi=10.1002/14651858.CD005029.pub2}}</ref>
Usually it's  successfully treated with anticonvulsants such as
[[carbamazepine]]<ref>Information from the USA National library of medicine on carbamazepine[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682237.html]</ref>
or [[phenytoin]]<ref>Information from the USA National library of medicine on phenytoin[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682022.html]</ref>
but others such as [[gabapentin]]<ref>Information from the USA National library of medicine on gabapentin[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a694007.html]</ref> can be used.
<ref>{{cite journal |author=Solaro C, Messmer Uccelli M, Uccelli A, Leandri M, Mancardi GL |title=Low-dose gabapentin combined with either lamotrigine or carbamazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis |journal=Eur. Neurol.|volume=44 |issue=1 |pages=45-8 |year=2000 |pmid=10894995 |doi=}}</ref>
 
===Lhermittes's Sign and Dysesthesias===
 
Both Lhermitte's sign and painful dysesthesias usually respond well to treatment with [[carbamazepine]], [[clonazepam]] or [[amitriptyline]].<ref>Information from the USA National library of medicine on clonazepam[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682279.html]</ref><ref>Information from the USA National library of medicine on amitriptyline[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682388.html]</ref><ref>{{cite journal|author=Moulin DE, Foley KM, Ebers GC |title=Pain syndromes in multiple sclerosis |journal=Neurology |volume=38 |issue=12|pages=1830-4 |year=1988 |pmid=2973568 |doi=}}</ref>
 
===Spasticity===
 
There is evidence, albeit limited, of the clinical effectiveness of [[baclofen]],<ref>;[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682530.html Baclofen oral.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-10-17]].</ref> [[dantrolene]],<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682576.html Dantrolene oral.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-10-17]].</ref> [[diazepam]],<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682047.html Diazepam.] US National Library of Medicine (Medline) ([[2005-07-01]]). Retrieved on [[2007-10-17]].</ref> and [[tizanidine]].<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601121.html Tizanidine.] US National Library of Medicine (Medline) ([[2005-07-01]]). Retrieved on [[2007-10-17]].</ref><ref name="pmid14636486">{{cite journal |author=Beard S, Hunn A, Wight J|title=Treatments for spasticity and pain in multiple sclerosis: a systematic review |journal=Health technology assessment (Winchester, England) |volume=7 |issue=40 |pages=iii, ix–x, 1–111 |year=2003 |pmid=14636486 |doi=}}</ref><ref name="pmid12166503">{{cite journal |author=Paisley S, Beard S, Hunn A, Wight J |title=Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review |journal=Mult. Scler. |volume=8 |issue=4 |pages=319–29 |year=2002|pmid=12166503 |doi=}}</ref> In the most complicated cases [[intrathecal]] injections of baclofen can be used.<ref name="pmid8529173">{{cite journal |author=Becker WJ, Harris CJ, Long ML, Ablett DP, Klein GM, DeForge DA |title=Long-term intrathecal baclofen therapy in patients with intractable spasticity |journal=The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques |volume=22 |issue=3 |pages=208–17 |year=1995 |pmid=8529173 |doi=}}</ref>
 
===Transverse Myelitis===
 
Treatment is usually symptomatic only, corticosteroids being used with limited success.
 
===Tremor and Ataxia===
 
In the treatment of tremor many medications have been proposed; however their efficacy is very limited. Medications that have been reported to provide some relief are [[isoniazid]],<ref>{{cite journal |author=Bozek CB, Kastrukoff LF, Wright JM, Perry TL, Larsen TA |title=A controlled trial of isoniazid therapy for action tremor in multiple sclerosis |journal=J. Neurol. |volume=234 |issue=1|pages=36-9 |year=1987 |pmid=3546605 |doi=}}</ref><ref>{{cite journal |author=Duquette P, Pleines J, du Souich P |title=Isoniazid for tremor in multiple sclerosis: a controlled trial |journal=Neurology |volume=35 |issue=12 |pages=1772-5 |year=1985 |pmid=3906430|doi=}}</ref><ref>{{cite journal |author=Hallett M, Lindsey JW, Adelstein BD, Riley PO |title=Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis |journal=Neurology |volume=35 |issue=9 |pages=1374-7 |year=1985|pmid=3895037 |doi=}}</ref><ref>Information from the USA National library of medicine on Isoniazid
[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682401.html]</ref> [[carbamazepine]],<ref>Information from the USA National library of medicine on carbamazepine [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682237.html]</ref> [[propranolol]],<ref>{{cite journal |author=Koller WC |title=Pharmacologic trials in the treatment of cerebellar tremor|journal=Arch. Neurol. |volume=41 |issue=3 |pages=280-1 |year=1984 |pmid=6365047 |doi=}}</ref><ref>{{cite journal |author=Sechi GP, Zuddas M, Piredda M, Agnetti V, Sau G, Piras ML, Tanca S, Rosati G |title=Treatment of cerebellar tremors with carbamazepine: a controlled trial with long-term follow-up |journal=Neurology |volume=39 |issue=8 |pages=1113-5 |year=1989 |pmid=2668787|doi=}}</ref><ref>Information from the USA National library of medicine on propanolol[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682607.html]</ref> and gluthetimide,<ref>{{cite journal |author=Aisen ML, Holzer M, Rosen M, Dietz M, McDowell F |title=Glutethimide treatment of disabling action tremor in patients with multiple sclerosis and traumatic brain injury |journal=Arch. Neurol. |volume=48 |issue=5 |pages=513-5 |year=1991 |pmid=2021365 |doi=}}</ref> but published evidence of effectiveness is very limited.<ref>{{cite journal |author=Mills RJ, Yap L, Young CA |title=Treatment for ataxia in multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD005029 |year=2007|pmid=17253537 |doi=10.1002/14651858.CD005029.pub2}}</ref>
<gallery perrow="2">
Image:Alemtuzumab Fab 1CE1.png| Chemical structure of [[alemtuzumab]]
 
Image:Injection 23.JPG| Disease-modifying treatments are expensive and require frequent injections.
</gallery>


==References==
==References==
{{reflist|2}}
{{reflist|2}}
{{WH}}
{{WS}}


[[Category:Primary care]]
[[Category:Neurology]]
[[Category:Neurology]]
[[Category:Orthopedics]]
[[Category:Orthopedics]]
[[Category:Rheumatology]]
[[Category:Rheumatology]]
{{WH}}
{{WS}}

Latest revision as of 22:47, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [9]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.

Overview

The predominant therapy for multiple sclerosis is disease-modifying treatment in relapsing-remitting multiple sclerosis, immunosuppressive threpay in progressive multiple sclerosis and Glucocorticoid therapy in acute exacerbation.

Medical Therapy

The predominant therapy for multiple sclerosis is:

Disease-modifying treatment of relapsing-remitting multiple sclerosis

Relapsing-remitting type of MS can be treated with disease modifying therapy (DMT) in order to reduce the rate of attack and disease progression.[1][2]

Infusion therapy:

Injectable therapies:

Oral therapies:

Treatment of progressive multiple sclerosis

Treatment of acute exacerbation of multiple sclerosis

Symptom management

References

  1. ↑ Capra R, Cordioli C, Rasia S, Gallo F, Signori A, Sormani MP (November 2017). "Assessing long-term prognosis improvement as a consequence of treatment pattern changes in MS". Mult. Scler. 23 (13): 1757–1761. doi:10.1177/1352458516687402. PMID 28080255.
  2. ↑ Lizak N, Lugaresi A, Alroughani R, Lechner-Scott J, Slee M, Havrdova E, Horakova D, Trojano M, Izquierdo G, Duquette P, Girard M, Prat A, Grammond P, Hupperts R, Grand'Maison F, Sola P, Pucci E, Bergamaschi R, Oreja-Guevara C, Van Pesch V, Ramo C, Spitaleri D, Iuliano G, Boz C, Granella F, Olascoaga J, Verheul F, Rozsa C, Cristiano E, Flechter S, Hodgkinson S, Amato MP, Deri N, Jokubaitis V, Spelman T, Butzkueven H, Kalincik T (March 2017). "Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis". J. Neurol. Neurosurg. Psychiatry. 88 (3): 196–203. doi:10.1136/jnnp-2016-313976. PMID 27683916.
  3. ↑ Rice GP, Hartung HP, Calabresi PA (April 2005). "Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale". Neurology. 64 (8): 1336–42. doi:10.1212/01.WNL.0000158329.30470.D0. PMID 15851719.
  4. ↑ Hynes RO (February 1987). "Integrins: a family of cell surface receptors". Cell. 48 (4): 549–54. PMID 3028640.
  5. ↑ 5.0 5.1 Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N (March 1992). "Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin". Nature. 356 (6364): 63–6. doi:10.1038/356063a0. PMID 1538783.
  6. ↑ Kent SJ, Karlik SJ, Cannon C, Hines DK, Yednock TA, Fritz LC, Horner HC (April 1995). "A monoclonal antibody to alpha 4 integrin suppresses and reverses active experimental allergic encephalomyelitis". J. Neuroimmunol. 58 (1): 1–10. PMID 7730443.
  7. ↑ Ruck T, Bittner S, Wiendl H, Meuth SG (July 2015). "Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond". Int J Mol Sci. 16 (7): 16414–39. doi:10.3390/ijms160716414. PMC 4519957. PMID 26204829.
  8. ↑ Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK (October 2008). "Alemtuzumab vs. interferon beta-1a in early multiple sclerosis". N. Engl. J. Med. 359 (17): 1786–801. doi:10.1056/NEJMoa0802670. PMID 18946064.
  9. ↑ Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA (November 2012). "Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial". Lancet. 380 (9856): 1819–28. doi:10.1016/S0140-6736(12)61769-3. PMID 23122652.
  10. ↑ Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L (January 2017). "Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis". N. Engl. J. Med. 376 (3): 221–234. doi:10.1056/NEJMoa1601277. PMID 28002679.
  11. ↑ Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A, Barkhof F, Yin M, Leppert D, Glanzman R, Tinbergen J, Hauser SL (November 2011). "Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial". Lancet. 378 (9805): 1779–87. doi:10.1016/S0140-6736(11)61649-8. PMID 22047971.
  12. ↑ Goodin DS, Arnason BG, Coyle PK, Frohman EM, Paty DW (November 2003). "The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology". Neurology. 61 (10): 1332–8. PMID 14638950.
  13. ↑ Kasper LH, Reder AT (August 2014). "Immunomodulatory activity of interferon-beta". Ann Clin Transl Neurol. 1 (8): 622–31. doi:10.1002/acn3.84. PMC 4184564. PMID 25356432.
  14. ↑ "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. 45 (7): 1277–85. July 1995. PMID 7617182.
  15. ↑ "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. 352 (9139): 1498–504. November 1998. PMID 9820297.
  16. ↑ Clanet M, Radue EW, Kappos L, Hartung HP, Hohlfeld R, Sandberg-Wollheim M, Kooijmans-Coutinho MF, Tsao EC, Sandrock AW (November 2002). "A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS". Neurology. 59 (10): 1507–17. PMID 12451189.
  17. ↑ Arnon R, Aharoni R (October 2004). "Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications". Proc. Natl. Acad. Sci. U.S.A. 101 Suppl 2: 14593–8. doi:10.1073/pnas.0404887101. PMC 521994. PMID 15371592.
  18. ↑ Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB (July 1995). "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. 45 (7): 1268–76. PMID 7617181.
  19. ↑ Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, Robinson R, Riester K, Rana J, Elkins J, O'Neill G (June 2013). "Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial". Lancet. 381 (9884): 2167–75. doi:10.1016/S0140-6736(12)62190-4. PMID 23562009.
  20. ↑ Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT (September 2012). "Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis". N. Engl. J. Med. 367 (12): 1087–97. doi:10.1056/NEJMoa1206328. PMID 22992072.
  21. ↑ Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT (September 2012). "Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis". N. Engl. J. Med. 367 (12): 1098–107. doi:10.1056/NEJMoa1114287. PMID 22992073.
  22. ↑ Xu Z, Zhang F, Sun F, Gu K, Dong S, He D (April 2015). "Dimethyl fumarate for multiple sclerosis". Cochrane Database Syst Rev (4): CD011076. doi:10.1002/14651858.CD011076.pub2. PMID 25900414.
  23. ↑ Zeyda M, Poglitsch M, Geyeregger R, Smolen JS, Zlabinger GJ, Hörl WH, Waldhäusl W, Stulnig TM, Säemann MD (September 2005). "Disruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formation". Arthritis Rheum. 52 (9): 2730–9. doi:10.1002/art.21255. PMID 16142756.
  24. ↑ 24.0 24.1 O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS (October 2011). "Randomized trial of oral teriflunomide for relapsing multiple sclerosis". N. Engl. J. Med. 365 (14): 1293–303. doi:10.1056/NEJMoa1014656. PMID 21991951.
  25. ↑ He D, Zhang C, Zhao X, Zhang Y, Dai Q, Li Y, Chu L (March 2016). "Teriflunomide for multiple sclerosis". Cochrane Database Syst Rev. 3: CD009882. doi:10.1002/14651858.CD009882.pub3. PMID 27003123.
  26. ↑ O'Connor PW, Li D, Freedman MS, Bar-Or A, Rice GP, Confavreux C, Paty DW, Stewart JA, Scheyer R (March 2006). "A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses". Neurology. 66 (6): 894–900. doi:10.1212/01.wnl.0000203121.04509.31. PMID 16567708.
  27. ↑ O'Connor P, Comi G, Freedman MS, Miller AE, Kappos L, Bouchard JP, Lebrun-Frenay C, Mares J, Benamor M, Thangavelu K, Liang J, Truffinet P, Lawson VJ, Wolinsky JS (March 2016). "Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study". Neurology. 86 (10): 920–30. doi:10.1212/WNL.0000000000002441. PMC 4782117. PMID 26865517.
  28. ↑ Cohen JA, Chun J (May 2011). "Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis". Ann. Neurol. 69 (5): 759–77. doi:10.1002/ana.22426. PMID 21520239.
  29. ↑ La Mantia L, Tramacere I, Firwana B, Pacchetti I, Palumbo R, Filippini G (April 2016). "Fingolimod for relapsing-remitting multiple sclerosis". Cochrane Database Syst Rev. 4: CD009371. doi:10.1002/14651858.CD009371.pub2. PMID 27091121.
  30. ↑ Gonsette RE, Demonty L, Delmotte P (February 1977). "Intensive immunosuppression with cyclophosphamide in multiple sclerosis. Follow up of 110 patients for 2-6 years". J. Neurol. 214 (3): 173–81. PMID 65452.
  31. ↑ Hommers OR, Lamers KJ, Reekers P (1980). "Effect of intensive immunosuppression on the course of chronic progressive multiple sclerosis". J. Neurol. 223 (3): 177–90. PMID 6157011.
  32. ↑ Mertin J, Rudge P, Kremer M, Healey MJ, Knight SC, Compston A, Batchelor JR, Thompson EJ, Halliday AM, Denman M, Medawar PB (August 1982). "Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report". Lancet. 2 (8294): 351–4. PMID 6124759.
  33. ↑ Cook SD, Devereux C, Troiano R, Hafstein MP, Zito G, Hernandez E, Lavenhar M, Vidaver R, Dowling PC (June 1986). "Effect of total lymphoid irradiation in chronic progressive multiple sclerosis". Lancet. 1 (8495): 1405–9. PMID 2872516.
  34. ↑ "Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group". Ann. Neurol. 27 (6): 591–605. June 1990. doi:10.1002/ana.410270603. PMID 2193613.
  35. ↑ Goodkin DE, Rudick RA, VanderBrug Medendorp S, Daughtry MM, Schwetz KM, Fischer J, Van Dyke C (January 1995). "Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis". Ann. Neurol. 37 (1): 30–40. doi:10.1002/ana.410370108. PMID 7818255.
  36. ↑ Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J, Beutler E (July 1994). "Cladribine in treatment of chronic progressive multiple sclerosis". Lancet. 344 (8914): 9–13. PMID 7912347.
  37. ↑ Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, Mills JA, Weiner HL (January 1983). "Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH". N. Engl. J. Med. 308 (4): 173–80. doi:10.1056/NEJM198301273080401. PMID 6294517.
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  90. ↑ Mills RJ, Yap L, Young CA (2007). "Treatment for ataxia in multiple sclerosis". Cochrane database of systematic reviews (Online) (1): CD005029. doi:10.1002/14651858.CD005029.pub2. PMID 17253537.

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