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| {{SI}}
| | #redirect[[Treatment of multiple sclerosis]] |
| {{CMG}}
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| '''Associate Editors-In-Chief:''' {{CZ}}
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| ==Background==
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| Although there is no known cure for [[multiple sclerosis]] (MS), several '''therapies for multiple sclerosis''' have proven helpful. Multiple sclerosis is a [[chronic (medicine)|chronic]] [[Inflammation|inflammatory]] [[demyelinating disease]] that affects the [[Central Nervous System|central nervous system]] (CNS).
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| The most common initial course of the disease is the relapsing-remitting subtype, which is characterized by unpredictable attacks ([[relapse]]s) followed by periods of relative remission with no new signs of disease activity. After some years, many of the people who have this subtype begin to experience neurologic decline without acute relapses as the secondary progressive subtype. Other, less common, courses of the disease are the primary progressive (decline from the beginning without attacks) and the progressive-relapsing (steady neurologic decline and superimposed attacks). Different therapies are used for patients experiencing acute attacks, for patients who have the relapsing-remitting subtype, for patients who have the progressive subtypes, for patients without a [[diagnosis]] of MS who have a [[Demyelinating disease|demyelinating]] event, and for managing the various consequences of MS.
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| The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS have several [[adverse effect (medicine)|adverse effects]], and many possible therapies are still under investigation. At the same time different [[Alternative medicine|alternative treatments]] are pursued by many patients, despite the paucity of supporting, comparable, replicated scientific study.
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| This article focuses on therapies for standard MS; [[idiopathic inflammatory demyelinating diseases|borderline forms of MS]] have particular treatments that are excluded.
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| == Management of acute attacks ==
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| [[Image:Methylprednisolone.svg|right|thumb|Chemical structure of methylprednisolone. Corticosteroids are used during acute multiple sclerosis relapses.]]
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| During symptomatic attacks, patients may be hospitalized. As of 2007, 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. This is administered over a period of three to five days, and has a well-established [[efficacy]] in promoting a better recovery from [[disability]].<ref>{{cite journal |author=Sellebjerg F, Barnes D, Filippini G, ''et al.'' |title=EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses |journal=Eur. J. Neurol. |volume=12 |issue=12|pages=939–46 |year=2005 |pmid=16324087 |doi=10.1111/j.1468-1331.2005.01352.x}}</ref><ref>{{cite journal |author=Goodin DS, Frohman EM, Garmany GP, ''et al.'' |title=Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines |journal=Neurology |volume=58 |issue=2 |pages=169–78 |year=2002 |pmid=11805241 |doi=}}</ref>
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| 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: steroids produce a rapid improvement from disability, but this improvement only lasts up to thirty days following a clinical attack and is not evident thirty-six months after the attack. This treatment does not reduce the number of patients who subsequently develop a clinical [[relapse]].<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>
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| 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>
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| Recent studies suggest that steroids administered orally are just as effective at treating MS symptoms as intravenous treatment. However, short term treatment with high-dose intravenous corticosteroids does not seem to be attended by [[adverse drug reaction|adverse effect]]s; on the contrary, [[gastrointestinal]] symptoms and psychiatric disorders are more common with oral corticosteroids.<ref>{{cite journal |author=Filippini G, Brusaferri F, Sibley WA, ''et al.'' |title=Corticosteroids or ACTH for acute exacerbations in multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=4 |pages=CD001331 |year=2000 |pmid=11034713 |doi=}}</ref>
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| ==Disease-modifying treatments==
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| ===Clinically isolated syndrome===
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| The earliest clinical presentation of relapsing-remitting MS (RRMS) is the clinically isolated syndrome (CIS). During a CIS, there is a subacute attack suggestive of [[demyelination]] but the patient does not fulfill the [[McDonald criteria|criteria]] for diagnosis of multiple sclerosis.<ref name="pmid15847841">{{cite journal |author=Miller D, Barkhof F, Montalban X, Thompson A, Filippi M |title=Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis |journal=Lancet neurology |volume=4 |issue=5 |pages=281–8 |year=2005 |pmid=15847841 |doi=10.1016/S1474-4422(05)70071-5}}</ref> Several studies have shown that treatment with [[interferon]]s during an initial attack can decrease the chance that a patient will develop MS. These results support the use of interferon after a first clinical demyelinating event and indicate that there may be modest beneficial effects of immediate treatment compared with delayed initiation of treatment.<ref>{{cite journal |author=Jacobs LD, Beck RW, Simon JH, ''et al.'' |title=Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group |journal=[[New England Journal of Medicine|N Engl J Med]] |volume=343 |issue=13 |pages=898–904 |year=2000 |pmid=11006365 |doi=}}</ref><ref>{{cite journal |author=Comi G, Filippi M, Barkhof F, ''et al.'' |title=Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study |journal=[[Lancet (journal)|Lancet]] |volume=357 |issue=9268 |pages=1576–82 |year=2001 |pmid=11377645 |doi=}}</ref><ref name="pmid17679016">{{cite journal |author=Kappos L, Freedman MS, Polman CH, ''et al.'' |title=Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study |journal=Lancet |volume=370 |issue=9585 |pages=389–97 |year=2007 |pmid=17679016 |doi=10.1016/S0140-6736(07)61194-5}}</ref>
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| ===Relapsing-remitting MS===
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| [[Image:Injection 23.JPG|left|thumb|Disease-modifying treatments are expensive and require frequent injections.]]
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| As of 2007, six disease-modifying treatments have been approved by regulatory agencies of different countries, including the U.S. [[Food and Drug Administration]] (FDA), the [[European Medicines Agency]] (EMEA) and the Japanese [[Ministry of Health, Labour and Welfare (Japan)|PMDA]]. Three are [[interferon]]s: two formulations of [[interferon beta-1a]] (trade names ''Avonex'' and ''Rebif''; the first given weekly, the latter three times a week),<ref name="interferon beta-1a intramuscular"> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a693040.html Interferon beta-1a Intramuscular Injection.] US National Library of Medicine (Medline) ([[2006-04-01]]). Retrieved on [[2007-09-02]].</ref><ref name="interferon beta-1a subcutaneous"> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a604005.html Interferon beta-1a Subcutaneous Injection.] US National Library of Medicine (Medline) ([[2004-04-01]]). Retrieved on [[2007-09-02]].</ref> and one of [[interferon beta-1b]] (U.S. trade name ''Betaseron'', in Europe and Japan ''Betaferon'').<ref name="interferon beta-1b"> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601151.html Interferon Beta-1b Injection.] US National Library of Medicine (Medline) ([[2005-07-01]]). Retrieved on [[2007-09-02]].</ref> Interferons are [[medication]]s derived from human [[cytokine]]s which help to regulate the [[immune system]]. A fourth medication is [[glatiramer acetate]] (''Copaxone''),<ref name="glatiramer"> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a603016.html Glatiramer injection.] US National Library of Medicine (Medline) ([[2003-07-01]]). Retrieved on [[2007-09-02]].</ref> a mixture of [[peptide|polypeptides]] which may protect important [[myelin]] [[protein]]s by substituting itself as the target of [[Autoimmunity|immune system attack]].<ref name="pmid17531858">{{cite journal |author=Ziemssen T, Schrempf W |title=Glatiramer acetate: mechanisms of action in multiple sclerosis |journal=Int. Rev. Neurobiol. |volume=79 |issue= |pages=537–70 |year=2007 |pmid=17531858 |doi=10.1016/S0074-7742(07)79024-4}}</ref>
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| The fifth medication, [[mitoxantrone]], is an [[immunosuppressant]] also used in [[chemotherapy|cancer chemotherapy]]. Finally, the sixth is [[natalizumab]] (marketed as ''Tysabri''), a [[Monoclonal antibody therapy|monoclonal antibody]].<ref name="natalizumab"> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a605006.html Natalizumab Injection.] US National Library of Medicine (Medline) ([[2006-10-01]]). Retrieved on [[2007-09-02]].</ref>
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| All six medications are modestly effective at decreasing the number of attacks and slowing progression to disability, although they differ in their efficacy rate and studies of their long-term effects are still lacking.<ref name="pmid17627671">{{cite journal |author=Ruggieri M, Avolio C, Livrea P, Trojano M |title=Glatiramer acetate in multiple sclerosis: a review |journal=CNS Drug Rev |volume=13 |issue=2 |pages=178–91 |year=2007 |pmid=17627671 |doi=10.1111/j.1527-3458.2007.00010.x}}</ref><ref name="pmid14974077">{{cite journal |author=Munari L, Lovati R, Boiko A |title=Therapy with glatiramer acetate for multiple sclerosis |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD004678 |year=2004 |pmid=14974077 |doi=10.1002/14651858.CD004678}}</ref><ref name="pmid11687131">{{cite journal |author=Rice GP, Incorvaia B, Munari L, ''et al'' |title=Interferon in relapsing-remitting multiple sclerosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002002 |year=2001 |pmid=11687131 |doi=}}</ref><ref name="pmid16235298">{{cite journal |author=Martinelli Boneschi F, Rovaris M, Capra R, Comi G |title=Mitoxantrone for multiple sclerosis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD002127 |year=2005 |pmid=16235298 |doi=10.1002/14651858.CD002127.pub2}}</ref> Comparisons between immunomodulators (all but mitoxantrone) show that the most effective is natalizumab, .<ref name="pmid17350652">{{cite journal |author=Johnson KP |title=Control of multiple sclerosis relapses with immunomodulating agents |journal=J. Neurol. Sci. |volume=256 Suppl 1 |issue= |pages=S23–8 |year=2007 |pmid=17350652 |doi=10.1016/j.jns.2007.01.060}}</ref>
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| Mitoxantrone is probably the most effective of them all;<ref>{{cite journal |author=Gonsette RE |title=Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis |journal=Expert opinion on pharmacotherapy |volume=8 |issue=8 |pages=1103–16 |year=2007 |pmid=17516874 |doi=10.1517/14656566.8.8.1103}}</ref> however, its use is limited by severe [[cardiotoxicity]].<ref name="pmid16503747">{{cite journal |author=Murray TJ |title=The cardiac effects of mitoxantrone: do the benefits in multiple sclerosis outweigh the risks? |journal=Expert opinion on drug safety |volume=5 |issue=2 |pages=265–74 |year=2006 |pmid=16503747 |doi=10.1517/14740338.5.2.265}}</ref> This is the reason why it is mainly used to treat MS patients who have worsening relapsing-remitting or secondary progressive multiple sclerosis despite prior therapy with interferons or glatiramer acetate.
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| Medications also differ in ease of use, price and side effects.<ref>[http://www.peacehealth.org/kbase/dp/topic/tf2571/dp.htm Should I have disease-modifying therapy for multiple sclerosis?] Peace Health ([[2006-03-23]]). Retrieved on [[2007-10-23]].</ref> All of these therapies are expensive and require frequent [[Injection (medicine)|injection]]s, with ''Tysabri'' given as [[intravenous]] infusions every four weeks,<ref name="natalizumab"> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a605006.html Natalizumab Injection.] US National Library of Medicine (Medline) ([[2006-10-01]]). Retrieved on [[2007-09-02]].</ref> ''Avonex'' requiring weekly injections,<ref name="interferon beta-1a intramuscular"/> ''Rebif'' three times a week,<ref name="interferon beta-1a subcutaneous"/> and ''Copaxone'' and ''Betaseron'' daily injections.<ref name="glatiramer"/><ref name="interferon beta-1b"/>
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| Mitoxantrone is intravenously administered every three months as a slow [[Intravenous therapy|infusion]] over at least thirty minutes.
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| Even with appropriate use of medication, most patients with relapsing-remitting MS still suffer from some attacks and subsequent disability.
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| === Progressive MS ===
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| [[Image:Mitoxantrone skeletal.svg|right|thumb|Chemical structure of mitoxantrone. In 2007 it was the only approved treatment for secondary progressive multiple sclerosis.]]
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| Treatment of progressive MS is more difficult than relapsing-remitting MS, and many patients do not respond to any available therapy. A wide range of medications have been used to try to slow the progression of the disease.
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| [[Mitoxantrone]] has shown positive effects in patients with a secondary progressive and progressive relapsing courses. It is moderately effective in reducing the progression of the disease and the frequency of relapses in patients in short-term follow-up.<ref name="pmid16235298">{{cite journal |author=Martinelli Boneschi F, Rovaris M, Capra R, Comi G |title=Mitoxantrone for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=4 |pages=CD002127 |year=2005 |pmid=16235298 |doi=10.1002/14651858.CD002127.pub2}}</ref> In 2007 it was the only medication approved for secondary progressive and progressive relapsing multiple sclerosis; however, it causes dose-dependent [[cardiotoxicity|cardiac toxicity]] which limits its long-term use. Interferon-beta-1b slowed progression of the disease in one clinical trial for secondary progressive MS, but not in another. However, both studies demonstrated that interferon recipients had fewer relapses and less disease activity, as assessed by [[magnetic resonance imaging]] (MRI). Therefore, interferons show promise in treating secondary progressive MS, but more data is needed to support their widespread use.<ref name="pmid15182221">{{cite journal |author=McCormack PL, Scott LJ |title=Interferon-beta-1b: a review of its use in relapsing-remitting and secondary progressive multiple sclerosis |journal=CNS drugs |volume=18 |issue=8 |pages=521–46 |year=2004 |pmid=15182221 |doi=}}</ref>
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| Several trials have been designed specifically for primary progressive multiple sclerosis (PPMS), including trials with [[interferon]]s and [[mitoxantrone]], a phase III trial of [[glatiramer acetate]], and an open-label study of [[riluzole]].<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a696013.html Riluzole.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-09-02]].</ref> Patients with PPMS have also been included in trials of [[azathioprine]],<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682167.html Azathioprine.] US National Library of Medicine (Medline) ([[2004-04-01]]). Retrieved on [[2007-09-02]].</ref> [[methotrexate]],<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682019.html Methotrexate.] US National Library of Medicine (Medline) ([[2006-10-01]]). Retrieved on [[2007-09-02]].</ref> [[cladribine]],<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a693015.html Cladribine.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-09-02]].</ref> [[intravenous immunoglobulin]], [[cyclophosphamide]],<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682080.html Cyclophosphamide.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-09-02]].</ref> and studies of [[Hematopoietic stem cell|haematopoietic]] [[stem cell transplantation]]. However, no treatment in these trials has been proven definitively to modify the course of the disease.<ref name="pmid15907149">{{cite journal |author=Leary SM, Thompson AJ |title=Primary progressive multiple sclerosis: current and future treatment options |journal=CNS drugs |volume=19 |issue=5 |pages=369–76 |year=2005 |pmid=15907149 |doi=}}</ref>
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| ===Side effects of treatments===
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| [[Image:Implant.png|right|thumb|Injectable medications can produce irritation or bruises at injection site. The bruise depicted was produced by a subcutaneous injection.]]
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| Both the [[interferon]]s and [[glatiramer acetate]] are available only in injectable forms, and both can cause irritation at the injection site.
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| [[Interferon]]s are produced in the body during illnesses such as [[influenza]] in order to help fight the infection.<ref name="pmid17131933">{{cite journal |author=Sládková T, Kostolanský F |title=The role of cytokines in the immune response to influenza A virus infection |journal=Acta Virol. |volume=50 |issue=3 |pages=151–62 |year=2006 |pmid=17131933 |doi=}}</ref> They are responsible for the [[fever]], [[myalgia|muscle aches]], [[fatigue (medical)|fatigue]], and [[headache]] common during influenza infections. Many patients report influenza-like symptoms when using interferon to fight MS. This reaction often lessens over time and can be treated with over-the-counter fever reducers/pain relievers like [[paracetamol]] (known in the U.S. as acetaminophen),<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a681004.html Acetaminophen.] US National Library of Medicine (Medline) ([[2007-07-01]]). Retrieved on [[2007-09-02]].</ref> [[ibuprofen]],<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682159.html Ibuprofen.] US National Library of Medicine (Medline) ([[2007-03-01]]). Retrieved on [[2007-09-02]].</ref> and [[naproxen]].<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a681029.html Naproxen.] US National Library of Medicine (Medline) ([[2006-01-01]]). Retrieved on [[2007-09-02]].</ref> Rare, but potentially serious, [[liver]] function abnormalities have also been reported with interferons, requiring that all patients treated regularly be monitored with [[liver function tests]] to ensure safe use.<ref>Betaseron [package insert]. Montville, NJ: Berlex Inc; 2003</ref><ref>Rebif [package insert]. Rockland, MA: Serono Inc; 2005.</ref><ref>Avonex [package insert]. Cambridge, MA: Biogen Inc; 2003</ref> Interferon therapy has also been shown to induce the production of anti-IFN neutralizing [[antibodies]] (NAb), usually in the second 6 months of treatment, in 3 to 45% of treated patients. However, the clinical consequences of the presence of antibodies are presently unclear: it has not been proved that these antibodies reduce efficacy of treatment. Therefore, any treatment decision should be based only on the clinical response to therapy.<ref name="pmid15353281">{{cite journal |author=Durelli L, Ricci A |title=Anti-interferon antibodies in multiple sclerosis. Molecular basis and their impact on clinical efficacy |journal=Front. Biosci. |volume=9 |issue= |pages=2192–204 |year=2004 |pmid=15353281 |doi=}}</ref>
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| [[Glatiramer acetate]] is generally considered to be better tolerated than the interferons, although some patients taking glatiramer experience a post-injection reaction manifested by flushing, chest tightness, heart [[palpitation]]s, breathlessness, and anxiety, which usually lasts less than thirty minutes.<ref name="pmid14974077">{{cite journal |author=Munari L, Lovati R, Boiko A |title=Therapy with glatiramer acetate for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD004678 |year=2004 |pmid=14974077 |doi=10.1002/14651858.CD004678}}</ref>
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| [[Mitoxantrone]] therapy may be associated with immunosuppressive effects and [[hepatotoxicity|liver damage]]; however its most dangerous side effect is its dose-related [[cardiotoxicity|cardiac toxicity]]. Careful adherence to the administration and monitoring [[guideline (medical)|guidelines]] is therefore essential; this includes obtaining an [[echocardiogram]] and a [[complete blood count]] before treatment to decide whether the therapy is suitable for the patient or the risks are too great. It is recommended that mitoxantrone be discontinued at the first signs of heart damage, [[infection]] or liver dysfunction during therapy.<ref name="pmid16750460">{{cite journal |author=Fox EJ |title=Management of worsening multiple sclerosis with mitoxantrone: a review |journal=Clinical therapeutics |volume=28 |issue=4 |pages=461–74 |year=2006 |pmid=16750460 |doi=10.1016/j.clinthera.2006.04.013}}</ref>
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| In [[clinical trial|phase III studies]], [[natalizumab]] was highly effective and well tolerated; however, three cases of [[progressive multifocal leukoencephalopathy]] (PML) were identified in patients who had taken it in combination with interferons.<ref>{{cite journal |author=Kleinschmidt-DeMasters BK, Tyler KL |title=Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis |journal=[[New England Journal of Medicine|N Engl J Med]] |volume=353 |issue=4 |pages=369–74 |year=2005 |pmid=15947079 |doi=10.1056/NEJMoa051782}} [http://content.nejm.org/cgi/content/abstract/353/4/369 Free full text with registration]</ref><ref>{{cite journal |author=Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D |title=Progressive multifocal leukoencephalopathy in a patient treated with natalizumab |journal=N Engl J Med |volume=353 |issue=4 |pages=375–81 |year=2005 |pmid=15947078 |doi=10.1056/NEJMoa051847}} [http://content.nejm.org/cgi/content/abstract/353/4/375 Free full text with registration]</ref> PML is a rare and progressive [[demyelinating]] disease of the [[brain]] that typically causes permanent disability or death. It is caused by [[infection]] by the [[JC virus]] (JCV), a virus thought to be present in most healthy individuals, and at first its symptoms may be similar to a MS relapse. There are no known treatments for PML; but the sooner the [[immune system]] returns to normal the higher the probabilities for recovery will be. As natalizumab was the suspected cause for these three cases of PML, it was withdrawn from the markets. An intensive safety evaluation was conducted which concluded that there was a potential risk of PML in patients taking natalizumab in combination with interferons. In 2006, natalizumab was finally re-approved as a monotherapy for patients with relapsing forms of MS.<ref name="pmid17434098">{{cite journal |author=Kappos L, Bates D, Hartung HP, ''et al.'' |title=Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring |journal=Lancet neurology |volume=6 |issue=5 |pages=431–41 |year=2007 |pmid=17434098 |doi=10.1016/S1474-4422(07)70078-9}}</ref>
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| == Management of the effects of MS ==
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| Disease-modifying treatments only reduce the progression rate of the disease but do not stop it. As multiple sclerosis progresses, the symptomatology tends to increase. The disease is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and [[Disability|handicap]]. Management of these deficits is therefore very important.
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| Both drug therapy and [[neurorehabilitation]] have shown to ease the burden of some symptoms, even though neither influence disease progression. For other symptoms the efficacy of treatments is still very limited.<ref name="pmid16168933">{{cite journal |author=Kesselring J, Beer S |title=Symptomatic therapy and neurorehabilitation in multiple sclerosis |journal=Lancet neurology |volume=4 |issue=10 |pages=643–52 |year=2005 |pmid=16168933 |doi=10.1016/S1474-4422(05)70193-9}}</ref>
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| ===Neurorehabilitation===
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| [[Image:LegExtensionMachineExercise.JPG|right|thumb|Supervised physical therapy may be helpful to overcome some symptoms.]]
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| Although there are few studies of rehabilitation in MS,<ref name="pmid9473994">{{cite journal |author=Di Fabio RP, Soderberg J, Choi T, Hansen CR, Schapiro RT |title=Extended outpatient rehabilitation: its influence on symptom frequency, fatigue, and functional status for persons with progressive multiple sclerosis |journal=Archives of physical medicine and rehabilitation |volume=79 |issue=2 |pages=141–6 |year=1998 |pmid=9473994 |doi=}}</ref><ref name="pmid9921849">{{cite journal |author=Solari A, Filippini G, Gasco P, ''et al.'' |title=Physical rehabilitation has a positive effect on disability in multiple sclerosis patients |journal=Neurology |volume=52 |issue=1 |pages=57–62 |year=1999 |pmid=9921849 |doi=}}</ref> its general effectiveness, when conducted by a team of specialists, has been clearly demonstrated in other pathologies such as [[stroke]]<ref name="pmid10796318">{{cite journal |author= |title=Organised inpatient (stroke unit) care for stroke. Stroke Unit Trialists' Collaboration |journal=Cochrane database of systematic reviews (Online) |volume= |issue=2 |pages=CD000197 |year=2000 |pmid=10796318 |doi=}}</ref> or [[head trauma]].<ref name="pmid16034923">{{cite journal |author=Turner-Stokes L, Disler PB, Nair A, Wade DT |title=Multi-disciplinary rehabilitation for acquired brain injury in adults of working age |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD004170 |year=2005 |pmid=16034923 |doi=10.1002/14651858.CD004170.pub2}}</ref> As for any patient with neurologic deficits, a [[multidisciplinary]] approach is key to limiting and overcoming disability; however there are particular difficulties in specifying a ‘core team’ because people with MS may need help from almost any health profession or service at some point.<ref name="isbn = 1 86016 182 0">{{cite book | last = The Royal College of Physicians |title = Multiple Sclerosis. National clinical guideline for diagnosis and management in primary and secondary care | publisher = Sarum ColourView Group | date = 2004 | location = Salisbury, Wiltshire | isbn = 1 86016 182 0 }}[http://www.rcplondon.ac.uk/pubs/books/MS/MSfulldocument.pdf Free full text] ([[2004-08-13]]). Retrieved on [[2007-10-01]].</ref> [[Neurologist]]s will be the main [[physician]]s involved, but depending on the symptom, doctors of other medical specialties may also be helpful. Allied treatments such as [[physical therapy]]<ref name="pmid16533139">{{cite journal |author=Heesen C, Romberg A, Gold S, Schulz KH |title=Physical exercise in multiple sclerosis: supportive care or a putative disease-modifying treatment |journal=Expert review of neurotherapeutics |volume=6 |issue=3 |pages=347–55 |year=2006 |pmid=16533139 |doi=10.1586/14737175.6.3.347}}</ref><ref name="pmid15674920">{{cite journal |author=Rietberg MB, Brooks D, Uitdehaag BM, Kwakkel G |title=Exercise therapy for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD003980 |year=2005 |pmid=15674920 |doi=10.1002/14651858.CD003980.pub2}}</ref> or [[speech therapy]]<ref name="pmid9894114">{{cite journal |author=Merson RM, Rolnick MI |title=Speech-language pathology and dysphagia in multiple sclerosis |journal=Physical medicine and rehabilitation clinics of North America |volume=9 |issue=3 |pages=631–41 |year=1998 |pmid=9894114 |doi=}}</ref> can also help to manage some symptoms and maintain [[quality of life]]. Treatment of [[neuropsychiatry|neuropsychiatric]] symptoms such as emotional distress and [[clinical depression]] should involve [[mental health]] professionals such as [[therapist]]s, [[psychologist]]s, and [[psychiatrist]]s,<ref name="pmid17415083">{{cite journal |author=Ghaffar O, Feinstein A |title=The neuropsychiatry of multiple sclerosis: a review of recent developments |journal=Curr Opin Psychiatry |volume=20 |issue=3 |pages=278–85 |year=2007 |pmid=17415083 |doi=10.1097/YCO.0b013e3280eb10d7}}</ref> while [[neuropsychologist]]s can help to evaluate and manage [[cognitive deficit]]s.<ref name="pmid17226744">{{cite journal |author=Benedict RH, Bobholz JH |title=Multiple sclerosis |journal=Seminars in neurology |volume=27 |issue=1 |pages=78–85 |year=2007 |pmid=17226744 |doi=10.1055/s-2006-956758}}</ref>
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| Although [[occupational therapy]] has shown its efficacy in other chronic neurologic conditions<ref name="pmid15859525">{{cite journal |author=Steultjens EM, Dekker J, Bouter LM, Leemrijse CJ, van den Ende CH |title=Evidence of the efficacy of occupational therapy in different conditions: an overview of systematic reviews |journal=Clinical rehabilitation |volume=19 |issue=3 |pages=247–54 |year=2005 |pmid=15859525 |doi=}}</ref> and some preliminary data suggests that it may be useful in MS,<ref name="pmid11723974">{{cite journal |author=Baker NA, Tickle-Degnen L |title=The effectiveness of physical, psychological, and functional interventions in treating clients with multiple sclerosis: a meta-analysis |journal=The American journal of occupational therapy. : official publication of the American Occupational Therapy Association |volume=55 |issue=3 |pages=324–31 |year=2001 |pmid=11723974 |doi=}}</ref> there are not sufficient randomized controlled studies to establish its effectiveness.<ref name="pmid15859525"/><ref name="pmid12917976">{{cite journal |author=Steultjens EM, Dekker J, Bouter LM, Cardol M, Van de Nes JC, Van den Ende CH |title=Occupational therapy for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD003608 |year=2003 |pmid=12917976 |doi=10.1002/14651858.CD003608}}</ref>
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| ===Medical treatments for symptoms===
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| {{Further|[[Multiple sclerosis signs and symptoms]]}}
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| Multiple sclerosis can cause a variety of symptoms including changes in sensation ([[hypoesthesia]]), muscle weakness, abnormal muscle spasms, difficulty to move, difficulties with coordination and balance, problems in speech (known as [[dysarthria]]) or swallowing ([[dysphagia]]), visual problems ([[nystagmus]], [[optic neuritis]], or [[diplopia]]), [[fatigue (medical)|fatigue]] and acute or chronic [[pain]] syndromes, [[Urinary bladder|bladder]] and [[bowel]] difficulties, cognitive impairment, or emotional symptomatology (mainly [[clinical depression|depression]]). The main clinical measure of disability progression and severity of the symptoms is the [[Expanded Disability Status Scale]] or EDSS.<ref>{{cite journal |author=Kurtzke JF |title=Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) |journal=Neurology |volume=33 |issue=11 |pages=1444–52 |year=1983 |pmid=6685237 |doi=}}</ref> At the same time for each symptom there are different treatment options. Treatments should therefore be individualized depending both on the patient and the physician.
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| *'''Bladder''': pharmacological treatments for [[bladder]] problems vary greatly depending on the origin or type of dysfunction; however, some examples of 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> [[alfuzosin]] for retention,<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a604002.html Alfuzosin.] US National Library of Medicine (Medline) ([[2007-03-01]]). Retrieved on [[2007-09-02]].</ref> [[anticholinergic]]s such as [[trospium]] and [[flavoxate]] for [[urinary urgency|urgency]] and [[urinary incontinence|incontinence]],<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a604037.html Trospium.] US National Library of Medicine (Medline) ([[2005-01-01]]). Retrieved on [[2007-09-02]].</ref><ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682706.html Flavoxate.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-09-02]].</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=15 |year=2005 |pmid=15932348 |doi=10.1111/j.1600-0404.2005.00431.x}}</ref><ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682876.html Desmopressin.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-09-02]].</ref> Non-pharmacological treatments involve the use of [[pelvic floor]] muscle training, stimulation, [[biofeedback]], [[pessary|pessaries]], bladder retraining, and sometimes intermittent [[urinary catheterization|catheterization]].<ref>Frances M Diro ([[2006-10-11]]). [http://www.emedicine.com/neuro/topic673.htm Urological Management in Neurological Disease]. ''[[eMedicine]]''. [[WebMD]]. Retrieved on [[2007-09-02]].</ref>
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| *'''Bowel''': people with MS may suffer [[bowel]] problems in two ways: reduced gut mobility may follow from immobility and the drugs used to treat various impairments; and neurological control of [[defecation]] may be directly impaired.<ref name="isbn = 1 86016 182 0"/> Pain or difficulty with defecation can be helped with a diet change, oral [[laxative]]s or [[suppository|suppositories]] and [[enema]]s.<ref name="pmid12515563">{{cite journal |author=DasGupta R, Fowler CJ |title=Bladder, bowel and sexual dysfunction in multiple sclerosis: management strategies |journal=Drugs |volume=63 |issue=2 |pages=153–66 |year=2003 |pmid=12515563 |doi=}}</ref>
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| *'''Cognitive and emotional''': [[Neuropsychiatry|neuropsychiatric]] symptomatology is not rare in the course of the disease. Depression and [[anxiety]] appear in up to 80% of patients,<ref name="pmid9990556">{{cite journal |author=Diaz-Olavarrieta C, Cummings JL, Velazquez J, Garcia de la Cadena C |title=Neuropsychiatric manifestations of multiple sclerosis |journal=The Journal of neuropsychiatry and clinical neurosciences |volume=11 |issue=1 |pages=51–7 |year=1999 |pmid=9990556 |doi=}}</ref> and can be treated with a variety of antidepressants;<ref name="pmid17636666">{{cite journal |author=Gill D, Hatcher S |title=WITHDRAWN: Antidepressants for depression in medical illness |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD001312 |year=2007 |pmid=17636666 |doi=10.1002/14651858.CD001312.pub2}}</ref> [[selective serotonin reuptake inhibitor]]s (SSRIs) are the most commonly employed.<ref> [http://www.mayoclinic.com/print/ssris/MH00066/METHOD=print Selective serotonin reuptake inhibitors.] Mayo Clinic ([[2006-12-08]]). Retrieved on [[2007-09-02]].</ref> Other neuropsychiatric symptoms are [[euphoria (emotion)|euphoria]] and [[disinhibition]]. This [[wikt:dyad|dyad]] was called "euphoria sclerotica" by the first authors that described the disease during the 19th century, and affects 10% of patients.<ref name="pmid9482369">{{cite journal |author=Finger S |title=A happy state of mind: a history of mild elation, denial of disability, optimism, and laughing in multiple sclerosis |journal=Arch. Neurol. |volume=55 |issue=2 |pages=241–50 |year=1998 |pmid=9482369 |doi=}}</ref><ref name="pmid15377743">{{cite journal |author=Fishman I, Benedict RH, Bakshi R, Priore R, Weinstock-Guttman B |title=Construct validity and frequency of euphoria sclerotica in multiple sclerosis |journal=The Journal of neuropsychiatry and clinical neurosciences |volume=16 |issue=3 |pages=350–6 |year=2004 |pmid=15377743 |doi=10.1176/appi.neuropsych.16.3.350}}</ref> On the other hand, [[cognitive deficit]]s appear in approximately 50% of the people with the disease.<ref name="pmid3805250">{{cite journal |author=Rao SM |title=Neuropsychology of multiple sclerosis: a critical review |journal=Journal of clinical and experimental neuropsychology: official journal of the International Neuropsychological Society |volume=8 |issue=5 |pages=503–42 |year=1986 |pmid=3805250 |doi=}}</ref> [[Anticholinesterase]] drugs such as [[donepezil]]<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a697032.html Donepezil.] US National Library of Medicine (Medline) ([[2007-04-01]]). Retrieved on [[2007-09-02]].</ref>—commonly used in [[Alzheimer disease]]—although not approved yet for multiple sclerosis, have shown efficacy in improving cognitive functions.<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> Psychological interventions are also useful in the treatment of cognitive and emotional deficits.<ref name="pmid11777121">{{cite journal |author=Mohr DC, Boudewyn AC, Goodkin DE, Bostrom A, Epstein L |title=Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis |journal=Journal of consulting and clinical psychology |volume=69 |issue=6 |pages=942–9 |year=2001 |pmid=11777121 |doi=}}</ref><ref name="pmid11212135">{{cite journal |author=Benedict RH, Shapiro A, Priore R, Miller C, Munschauer F, Jacobs L |title=Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients |journal=Mult Scler |volume=6 |issue=6 |pages=391–6 |year=2000 |pmid=11212135 |doi=}}</ref><ref name="pmid16437487">{{cite journal |author=Thomas PW, Thomas S, Hillier C, Galvin K, Baker R |title=Psychological interventions for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD004431 |year=2006 |pmid=16437487 |doi=10.1002/14651858.CD004431.pub2}}</ref><ref name="pmid14561373">{{cite journal |author=Amato MP, Zipoli V |title=Clinical management of cognitive impairment in multiple sclerosis: a review of current evidence |journal=International MS journal / MS Forum |volume=10 |issue=3 |pages=72–83 |year=2003 |pmid=14561373 |doi=}}</ref>
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| *'''Dysphagia and dysarthria''': [[dysphagia]] is a difficulty with swallowing which may cause [[choking]] and [[pulmonary aspiration|aspiration]] of food or liquid into the [[lung]]s, while [[dysarthria]] is a [[neurological]] motor [[speech disorder]] characterized by poor control over the subsystems and muscles responsible for [[speech communication|speech]] ("articulation"). A language therapist may give advice on specific swallowing techniques, on adapting food consistencies and dietary intake, on techniques to improve and maintain speech production and clarity, and on alternative communication systems.<ref name="isbn = 1 86016 182 0"/><ref name="pmid9894114"/> In the case of advanced dysphagia, food can be supplied by a [[feeding tube|nasogastric tube]], which is a tube that goes through the nose directly to the stomach; or a [[percutaneous endoscopic gastrostomy]] (PEG), which is a procedure for placing a tube into the stomach and therefore administering food directly to it. This second system, although more [[Invasive (medical)|invasive]], has better results in the long term than nasogastric intake.<ref name="pmid10796343">{{cite journal |author=Bath PM, Bath FJ, Smithard DG |title=Interventions for dysphagia in acute stroke |journal=Cochrane database of systematic reviews (Online) |volume= |issue=2 |pages=CD000323 |year=2000 |pmid=10796343 |doi=}}</ref>
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| *'''Fatigue''': [[fatigue (medical)|fatigue]] is very common and disabling in MS, and at the same time it has a close relationship with depressive symptomatology.<ref name="pmid12814166">{{cite journal |author=Bakshi R |title=Fatigue associated with multiple sclerosis: diagnosis, impact and management |journal=Mult. Scler. |volume=9 |issue=3 |pages=219–27 |year=2003 |pmid=12814166 |doi=}}</ref> When depression is reduced fatigue also tends to improve, so patients should be evaluated for depression before other therapeutic approaches are used.<ref name="pmid12883103">{{cite journal |author=Mohr DC, Hart SL, Goldberg A |title=Effects of treatment for depression on fatigue in multiple sclerosis |journal=Psychosomatic medicine |volume=65 |issue=4 |pages=542–7 |year=2003 |pmid=12883103 |doi=}}</ref> In a similar way, other factors such as disturbed sleep, chronic pain, poor nutrition, or even some medications can contribute to fatigue; medical professionals are therefore encouraged to identify and modify them.<ref name="isbn = 1 86016 182 0"/> 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. Fatigue is therefore a very difficult symptom to manage.
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| *'''Pain''': [[acute (medical)|acute]] pain is mainly due to [[optic neuritis]] (with [[corticosteroids]] being the best treatment available), as well as [[trigeminal neuralgia]], [[Lhermitte's sign]], or [[dysesthesias]].<ref>{{cite journal |author=Kerns RD, Kassirer M, Otis J |title=Pain in multiple sclerosis: a biopsychosocial perspective |journal=Journal of rehabilitation research and development |volume=39 |issue=2 |pages=225–32 |year=2002 |pmid=12051466 |doi=}}</ref> [[Subacute]] pain is usually secondary to the disease and can be a consequence of spending too long in the same position, urinary retention, and infected skin ulcers, amongst others. Treatment will depend on cause. [[Chronic (medicine)|Chronic]] pain is very common and harder to treat as its most common cause is dysesthesias. Acute pain due to trigeminal neuralgia is usually successfully treated with anticonvulsants such as [[carbamazepine]]<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682237.html Carbamazepine.] US National Library of Medicine (Medline) ([[2007-05-01]]). Retrieved on [[2007-09-02]].</ref> or [[phenytoin]].<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682022.html Phenytoin]. US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-09-02]].</ref><ref>{{cite journal |author=Brisman R |title=Trigeminal neuralgia and multiple sclerosis |journal=Arch. Neurol. |volume=44 |issue=4 |pages=379–81 |year=1987 |pmid=3493757 |doi=}}</ref><ref>{{cite journal |author=Bayer DB, Stenger TG |title=Trigeminal neuralgia: an overview |journal=Oral Surg. Oral Med. Oral Pathol. |volume=48 |issue=5 |pages=393–9 |year=1979 |pmid=226915 |doi=}}</ref> Both Lhermitte's sign and painful dysesthesias usually respond to treatment with [[carbamazepine]], [[clonazepam]],<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682279.html Clonazepam.] US National Library of Medicine (Medline) ([[2003-04-01]]). Retrieved on [[2007-09-02]].</ref> or [[amitriptyline]].<ref> [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682388.html Amitriptyline.] US National Library of Medicine (Medline) ([[2007-08-01]]). Retrieved on [[2007-09-02]].</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> [[Sativex]] is approved for treatment of pain in MS in different countries, but due to its derivation from [[cannabis]], it is currently not available in others, such as the USA.<ref name="pmid17257464">{{cite journal |author=Iskedjian M, Bereza B, Gordon A, Piwko C, Einarson TR |title=Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain |journal=Current medical research and opinion |volume=23 |issue=1 |pages=17–24 |year=2007 |pmid=17257464 |doi=10.1185/030079906X158066}}</ref> This medication is also being investigated for the management of other MS symptoms, such as spasticity,<ref name="pmid16317825">{{cite journal |author=Perras C |title=Sativex for the management of multiple sclerosis symptoms |journal=Issues in emerging health technologies |volume= |issue=72 |pages=1–4 |year=2005 |pmid=16317825 |doi=}}</ref> and has shown long-term safety and efficacy.<ref name="pmid17086911">{{cite journal |author=Wade DT, Makela PM, House H, Bateman C, Robson P |title=Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis |journal=Mult. Scler. |volume=12 |issue=5 |pages=639–45 |year=2006 |pmid=17086911 |doi=}}</ref>
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| *'''Spasticity''': [[spasticity]] is characterised by increased stiffness and slowness in [[Limb (anatomy)|limb]] movement, the development of certain postures, an association with weakness of voluntary [[muscle]] power, and with involuntary and sometimes painful [[spasm]]s of limbs.<ref name="isbn = 1 86016 182 0"/> A physiotherapist can help to reduce spasticity and avoid the development of [[contracture]]s with techniques such as [[passive stretching]].<ref name="pmid10871810">{{cite journal |author=Cardini RG, Crippa AC, Cattaneo D |title=Update on multiple sclerosis rehabilitation |journal=J. Neurovirol. |volume=6 Suppl 2 |issue= |pages=S179–85 |year=2000 |pmid=10871810 |doi=}}</ref> 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> There are also [[palliative]] measures like [[casting]]s, [[splint (medical)|splints]] or customised seatings.<ref name="isbn = 1 86016 182 0"/>
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| *'''Vision''': different drugs as well as optic compensatory systems and prisms can be used to improve the symptoms of [[nystagmus]].<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=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> 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>
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| Unfortunately, other symptoms, such as [[ataxia]], [[tremor]] or [[sensory system|sensory losses]], do not have proven treatments.<ref name="isbn = 1 86016 182 0"/>
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| == Therapies under investigation ==
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| {{Main|Therapies under investigation for multiple sclerosis}}
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| Scientists continue their extensive efforts to create new and better therapies for MS. There are a number of treatments under investigation that may curtail attacks or improve function. Some of these treatments involve the combination of drugs that are already in use for multiple sclerosis, such as the combination of [[mitoxantrone]] and [[glatiramer acetate]] (''Copaxone'').<ref> [http://www.mxga-mstrial.co.uk United Kingdom early Mitoxantrone Copaxone trial.] Onyx Healthcare ([[2006-01-01]]). Retrieved on [[2007-09-02]].</ref> However most treatments already in clinical trials involve drugs that are used in other diseases. These are the cases of [[alemtuzumab]] (trade name ''Campath''),<ref> [http://www.genzyme.com/corp/media/GENZ%20PR-050207.asp Genzyme and Bayer HealthCare Announce Detailed Interim Two-Year Alemtuzumab in Multiple Sclerosis Data Presented at AAN.] Genzyme ([[2007-02-01]]). Retrieved on [[2007-09-02]].</ref> [[daclizumab]] (trade name ''Zenapax''),<ref> [http://www.pdl.com/index.cfm?navId=49 Daclizumab.] PDL Biopharma ([[2006-01-01]]). Retrieved on [[2007-09-02]].</ref> [[inosine]],<ref> [http://www.clinicaltrials.gov/ct/show/NCT00067327 Treatment of Multiple Sclerosis Using Over the Counter Inosine.] ClinicalTrials.gov ([[2006-03-16]]). Retrieved on [[2007-09-02]].</ref> or [[BG00012]].<ref>[http://www.clinicaltrials.gov/ct2/show/NCT00420212?term=biogen&recr=Open&rank=12 Efficacy and Safety of BG00012 in Relapsing-Remitting Multiple Sclerosis.] ClinicalTrials.gov ([[2007-09-01]]). Retrieved on [[2007-11-12]].</ref> Other drugs in clinical trials have been designed specifically for MS, like [[fingolimod]],<ref> [http://www.clinicaltrials.gov/ct/show/NCT00289978 Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis.] ClinicalTrials.gov ([[2006-02-09]]). Retrieved on [[2007-09-02]].</ref> [[laquinimod]],<ref name="pmid15781813">{{cite journal |author=Polman C, Barkhof F, Sandberg-Wollheim M, Linde A, Nordle O, Nederman T |title=Treatment with laquinimod reduces development of active MRI lesions in relapsing MS |journal=Neurology |volume=64 |issue=6 |pages=987–91 |year=2005 |pmid=15781813 |doi=10.1212/01.WNL.0000154520.48391.69}}</ref> or ''[[Neurovax]]''.<ref>{{cite journal |author=Darlington CL |title=Technology evaluation: NeuroVax, Immune Response Corp |journal=Curr. Opin. Mol. Ther. |volume=7 |issue=6 |pages=598–603 |year=2005 |pmid=16370383 |doi=}}</ref> Finally, there are also many basic investigations that in the future may be able to find new treatments. Examples of these are the studies trying to understand the influence of ''[[Chlamydophila pneumoniae]]'' or [[vitamin D]] in the origin of the disease,<ref>{{cite journal |author=Sriram S, Yao SY, Stratton C, Moses H, Narayana PA, Wolinsky JS |title=Pilot study to examine the effect of antibiotic therapy on MRI outcomes in RRMS |journal=J. Neurol. Sci. |volume=234 |issue=1–2 |pages=87–91 |year=2005 |pmid=15935383 |doi=10.1016/j.jns.2005.03.042}}</ref><ref>{{cite journal |author=Munger KL, Zhang SM, O'Reilly E, ''et al.'' |title=Vitamin D intake and incidence of multiple sclerosis |journal=Neurology |volume=62 |issue=1 |pages=60–5 |year=2004 |pmid=14718698 |doi=}}</ref> or preliminary investigations on the use of [[helminthic therapy]].<ref name="pmid17230481">{{cite journal |author=Correale J, Farez M. |title=Association between parasite infection and immune responses in multiple sclerosis. |journal=Annals of Neurology |volume=61 |issue=2 |pages=97–108 |year=2007 |pmid=17230481 |doi=}}</ref>
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| ==Alternative treatments==
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| [[Image:Cannabis sativa.jpg|left|thumb|Many patients use medical marijuana as an alternative treatment to help them alleviate some symptoms.]]
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| Different alternative treatments are pursued by many patients, despite the paucity of supporting, comparable, replicated scientific study.
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| Clinical and experimental data suggest that certain [[Diet (nutrition)|dietary]] regimens, particularly those including [[polyunsaturated fatty acid]]s, and [[vitamin]]s might improve outcomes in people with multiple sclerosis.<ref>{{cite journal |author=Schreibelt G, Musters RJ, Reijerkerk A, ''et al.'' |title=Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity |journal=J. Immunol. |volume=177 |issue=4 |pages=2630–7 |year=2006 |pmid=16888025 |doi=}}</ref><ref name="pmid16118655">{{cite journal |author=van Meeteren ME, Teunissen CE, Dijkstra CD, van Tol EA |title=Antioxidants and polyunsaturated fatty acids in multiple sclerosis |journal=European journal of clinical nutrition |volume=59 |issue=12 |pages=1347–61 |year=2005 |pmid=16118655 |doi=10.1038/sj.ejcn.1602255}}</ref> Many diets have been proposed for treating the symptoms of the disease. Patients have reported a decrease in symptoms after long-term application of changes in diet; however, no controlled trials have been able to prove their efficacy.<ref name="pmid17253500">{{cite journal |author=Farinotti M, Simi S, Di Pietrantonj C, ''et al.'' |title=Dietary interventions for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD004192 |year=2007 |pmid=17253500 |doi=10.1002/14651858.CD004192.pub2}}</ref> Even if these diets are genuinely beneficial for people with MS, it is uncertain whether this is due to any special traits of the diets or that they are simply beneficial for whole body health. Two examples of such diets are the [[Swank Multiple Sclerosis Diet]]<ref name="pmid1804476">{{cite journal |author=Swank RL |title=Multiple sclerosis: fat-oil relationship |journal=Nutrition (Burbank, Los Angeles County, Calif.) |volume=7 |issue=5 |pages=368–76 |year=1991 |pmid=1804476 |doi=}}</ref><ref name="pmid12591551">{{cite journal |author=Swank RL, Goodwin J |title=Review of MS patient survival on a Swank low saturated fat diet |journal=Nutrition (Burbank, Los Angeles County, Calif.) |volume=19 |issue=2 |pages=161–2 |year=2003 |pmid=12591551 |doi=}}</ref> and the [[Best Bet Diet (multiple sclerosis)|Best Bet Diet]].<ref> >[http://www.direct-ms.org/plannedresearch.html Direct-MS Society - Clinical trials proposal and description] Direct-MS. Retrieved on [[2007-11-08]].</ref>
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| [[Herbal medicine]] is another source of alternative treatments. Many patients use medical [[marijuana]] to help alleviate symptoms; however, the results of experimental studies are scarce. At least one subgroup experiencing greater disability appears to have derived some symptomatic benefit.<ref>{{cite journal |author=Chong MS, Wolff K, Wise K, Tanton C, Winstock A, Silber E |title=Cannabis use in patients with multiple sclerosis |journal=Mult. Scler. |volume=12 |issue=5 |pages=646–51 |year=2006 |pmid=17086912 |doi=}}</ref><ref>{{cite journal |author=Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, Nunn AJ, Teare LJ, Fox PJ, Thompson AJ |title=Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up |journal=J. Neurol. Neurosurg. Psychiatr. |volume=76 |issue=12 |pages=1664–9 |year=2005 |pmid=16291891 |doi=10.1136/jnnp.2005.070136}}</ref>
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| [[Hyperbaric oxygenation]] has been the subject of several small studies with heterogeneous results which, overall, do not support its use.<ref name="pmid14974004">{{cite journal |author=Bennett M, Heard R |title=Hyperbaric oxygen therapy for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD003057 |year=2004 |pmid=14974004 |doi=10.1002/14651858.CD003057.pub2}}</ref>
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| The [[Martial arts therapy|therapeutic practice of martial arts]] such as [[tai chi]], relaxation disciplines such as [[yoga]], or general exercise, seem to mitigate fatigue and improve quality of life.<ref name="pmid15184614">{{cite journal |author=Oken BS, Kishiyama S, Zajdel D, ''et al.'' |title=Randomized controlled trial of yoga and exercise in multiple sclerosis |journal=Neurology |volume=62 |issue=11 |pages=2058–64 |year=2004 |pmid=15184614 |doi=}}</ref> Some studies also show benefits on physical variables but more investigation is needed as they are usually of low quality.<ref name="pmid15006825">{{cite journal |author=Wang C, Collet JP, Lau J |title=The effect of Tai Chi on health outcomes in patients with chronic conditions: a systematic review |journal=[[Archives of Internal Medicine|Arch Intern Med]] |volume=164 |issue=5 |pages=493–501 |year=2004 |pmid=15006825 |doi=10.1001/archinte.164.5.493}}</ref>
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| ==Further reading==
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| '''Clinical guidelines''': [[clinical guideline]]s are documents with the aim of guiding decisions and criteria in specific areas of healthcare, as defined by an authoritative examination of current evidence ([[evidence-based medicine]]).
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| *{{cite book | last = The Royal College of Physicians |title = Multiple Sclerosis. National clinical guideline for diagnosis and management in primary and secondary care | publisher = Sarum ColourView Group | date = 2004 | location = Salisbury, Wiltshire | isbn = 1 86016 182 0 }}[http://www.rcplondon.ac.uk/pubs/books/MS/MSfulldocument.pdf Free full text] ([[2004-08-13]]). Retrieved on [[2007-10-01]].
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| *{{cite book | last = |title = Multiple sclerosis. Understanding NICE guidance. Information for people with multiple sclerosis, their families and carers, and the public | publisher = National Institute of Clinical Excellence | date = 2003 | location = London | isbn = 1-84257-445-0 }} [http://guidance.nice.org.uk/CG8/publicinfo/pdf/English/download.dspx Free full text] ([[2003-11-26]]). Retrieved on [[2007-10-25]].
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| ==Notes and references==
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| {{reflist|2}}
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| {{Multiple sclerosis}}
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| {{SIB}}
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| [[Category:Autoimmune diseases]]
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| [[Category:Multiple sclerosis]]
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| [[Category:Medical treatments]]
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| [[Category:Neurological disorders]]
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| [[es:Tratamiento de la esclerosis múltiple]]
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