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=== Treatment of progressive multiple sclerosis ===
=== Treatment of progressive multiple sclerosis ===
Studies show that [[Immunosuppression|immunosuppressive threpay]] including Total lymphoid irradiation<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>, [[Cyclosporine|cyclosporin]]<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>, [[Methotrexate]]<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>, [[Cladribine]]<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>, [[Cyclophosphamide]]<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>, [[Mitoxantrone]]<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>, [[Azathioprine]]<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>, [[Interferon]]<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>, [[Corticosteroid]]<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>, [[Intravenous immunoglobulin]]<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>, [[Plasma]] exchange<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>, [[bone marrow transplant]]<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>, Antiintegrin antibodies ([[natalizumab]])<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> 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>
Studies show that [[Immunosuppression|immunosuppressive threpay]] including Total lymphoid irradiation<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>, [[Cyclosporine|cyclosporin]]<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>, [[Methotrexate]]<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>, [[Cladribine]]<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>, [[Cyclophosphamide]]<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>, [[Mitoxantrone]]<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>, [[Azathioprine]]<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>, [[Interferon]]<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>, [[Corticosteroid]]<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>, [[Intravenous immunoglobulin]]<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>, [[Plasma]] exchange<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>, [[bone marrow transplant]]<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>, Antiintegrin antibodies ([[natalizumab]])<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> 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>  


=== Treatment of acute exacerbations of multiple sclerosis ===
=== Treatment of acute exacerbations of multiple sclerosis ===
Line 38: Line 38:
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>  
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>  


[[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> the [[side effects]] of this therapy include [[depression]] or [[mania]], [[infection]] and [[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>
[[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> the [[side effects]] of this therapy include [[depression]] or [[mania]], [[infection]] and [[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.


Medical management of few individual symptoms and/or signs is as follows :-
Medical management of few individual symptoms and/or signs is as follows :-

Revision as of 15:22, 2 March 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [15]

Overview

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

Studies show that immunosuppressive threpay including Total lymphoid irradiation[30], cyclosporin[31], Methotrexate[32], Cladribine[33], Cyclophosphamide[34], Mitoxantrone[35], Azathioprine[36], Interferon[37], Corticosteroid[38], Intravenous immunoglobulin[39], Plasma exchange[40], bone marrow transplant[41], Antiintegrin antibodies (natalizumab)[5] can be beneficial in progressive and sever case of multiple sclerosis.[42][43][44]

Treatment of acute exacerbations of multiple sclerosis

Management of acute attacks of multiple sclerosis may help patients to recover faster but has no effect in long term signs and symptoms.[45][46]

Glucocorticoid therapy: We commonly use 500 to 1000 mg of methylprednisolone daily.[47] the side effects of this therapy include depression or mania, infection and GI disturbance.[48] Multiple studies demonstrate that Plasma exchange can be beneficial in acute attacks of multiple sclerosis too.

Medical management of few individual symptoms and/or signs is as follows :-

Bladder

Treatment objectives are alleviation of symptoms of urinary dysfunction, treatment of urinary infections, reduction of complicating factors and preservation of renal function. Treatments can be classified in two main subtypes: pharmacological and non pharmacological.

Pharmacological treatments vary greatly depending on the origin or type of dysfunction; however some examples of the medications used are:[49] alfuzosin for retention,[50] trospium and flavoxate for urgency and incontinency,[51][52] or desmopressin for nocturia.[53][54]

Non pharmacological treatments involve the use of pelvic floor muscle training, stimulation biofeedback, pessaries, bladder training, and sometimes intermittent catheterization.[55]

Cognition

Interferons have demonstrated that can help to reduce cognitive limitations in multiple sclerosis.[56]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.[57][58][59]

Fatigue

There are also different medications used to treat fatigue; such as amantadine,[60][61] or pemoline [62][63] as well as psychological interventions of energy conservation;[64][65] but the effects of all of them are small. For this reason fatigue is a very difficult symptom to manage.

Internuclear Ophthalmoplegia

Different drugs as well as optic compensatory systems and prisms can be used to improve this symptoms.[66][67][68][69] Surgery can also be used in some cases for this problem.[70]

Optic Neuritis

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.

Trigeminal Neuralgia

Usually it's successfully treated with anticonvulsants such as carbamazepine[71] or phenytoin[72] but others such as gabapentin[73] can be used. [74]

Lhermittes's Sign and Dysesthesias

Both Lhermitte's sign and painful dysesthesias usually respond well to treatment with carbamazepine, clonazepam or amitriptyline.[75][76][77]

Spasticity

There is evidence, albeit limited, of the clinical effectiveness of baclofen,[78] dantrolene,[79] diazepam,[80] and tizanidine.[81][82][83] In the most complicated cases intrathecal injections of baclofen can be used.[84]

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,[85][86][87][88] carbamazepine,[89] propranolol,[90][91][92] and gluthetimide,[93] but published evidence of effectiveness is very limited.[94]

  • Chemical structure of alemtuzumab

    Chemical structure of alemtuzumab

  • Disease-modifying treatments are expensive and require frequent injections.

    Disease-modifying treatments are expensive and require frequent injections.

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.
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  94. ↑ 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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