Multiple sclerosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [9]

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 exacerbation 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.[40][49]

Symptom management

Bladder:

Bladder dysfunction due to detresor overactivity can be treated with antimuscarinic and anticholinergic drugs such as oxybutynin, tolterodine, propantheline, propiverine, fesoterodine and solifenacin.[50][51]

Cognition

Some of disease modifying treatments such as interferons, natalizumab and fingolimod seems to have a good effect on cognitive problems in MS patients. There is some evidence of the cholinesterase inhibitors (donepzil) being beneficial to MS patients with cognitive disorders.[52][53]

Fatigue

There are also different medications used to treat fatigue; such as amantadine,[54][55] or pemoline [56][57] as well as psychological interventions of energy conservation;[58][59] 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.[60][61][62][63] Surgery can also be used in some cases for this problem.[64]

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[65] or phenytoin[66] but others such as gabapentin[67] can be used. [68]

Lhermittes's Sign and Dysesthesias

Both Lhermitte's sign and painful dysesthesias usually respond well to treatment with carbamazepine, clonazepam or amitriptyline.[69][70][71]

Spasticity

There is evidence, albeit limited, of the clinical effectiveness of baclofen,[72] dantrolene,[73] diazepam,[74] and tizanidine.[75][76][77] In the most complicated cases intrathecal injections of baclofen can be used.[78]

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,[79][80][81][82] carbamazepine,[83] propranolol,[84][85][86] and gluthetimide,[87] but published evidence of effectiveness is very limited.[88]

  • 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.
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  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.
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  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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  17. ↑ Arnon R, Aharoni R (October 2004). "Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications". Proc. Natl. Acad. Sci. U.S.A. 101 Suppl 2: 14593–8. doi:10.1073/pnas.0404887101. PMC 521994. PMID 15371592.
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  19. ↑ Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, Robinson R, Riester K, Rana J, Elkins J, O'Neill G (June 2013). "Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial". Lancet. 381 (9884): 2167–75. doi:10.1016/S0140-6736(12)62190-4. PMID 23562009.
  20. ↑ Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT (September 2012). "Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis". N. Engl. J. Med. 367 (12): 1087–97. doi:10.1056/NEJMoa1206328. PMID 22992072.
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  66. ↑ Information from the USA National library of medicine on phenytoin[2]
  67. ↑ Information from the USA National library of medicine on gabapentin[3]
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  69. ↑ Information from the USA National library of medicine on clonazepam[4]
  70. ↑ Information from the USA National library of medicine on amitriptyline[5]
  71. ↑ Moulin DE, Foley KM, Ebers GC (1988). "Pain syndromes in multiple sclerosis". Neurology. 38 (12): 1830–4. PMID 2973568.
  72. ↑ ;Baclofen oral. US National Library of Medicine (Medline) (2003-04-01). Retrieved on 2007-10-17.
  73. ↑ Dantrolene oral. US National Library of Medicine (Medline) (2003-04-01). Retrieved on 2007-10-17.
  74. ↑ Diazepam. US National Library of Medicine (Medline) (2005-07-01). Retrieved on 2007-10-17.
  75. ↑ Tizanidine. US National Library of Medicine (Medline) (2005-07-01). Retrieved on 2007-10-17.
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  78. ↑ Becker WJ, Harris CJ, Long ML, Ablett DP, Klein GM, DeForge DA (1995). "Long-term intrathecal baclofen therapy in patients with intractable spasticity". The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 22 (3): 208–17. PMID 8529173.
  79. ↑ Bozek CB, Kastrukoff LF, Wright JM, Perry TL, Larsen TA (1987). "A controlled trial of isoniazid therapy for action tremor in multiple sclerosis". J. Neurol. 234 (1): 36–9. PMID 3546605.
  80. ↑ Duquette P, Pleines J, du Souich P (1985). "Isoniazid for tremor in multiple sclerosis: a controlled trial". Neurology. 35 (12): 1772–5. PMID 3906430.
  81. ↑ Hallett M, Lindsey JW, Adelstein BD, Riley PO (1985). "Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis". Neurology. 35 (9): 1374–7. PMID 3895037.
  82. ↑ Information from the USA National library of medicine on Isoniazid [6]
  83. ↑ Information from the USA National library of medicine on carbamazepine [7]
  84. ↑ Koller WC (1984). "Pharmacologic trials in the treatment of cerebellar tremor". Arch. Neurol. 41 (3): 280–1. PMID 6365047.
  85. ↑ Sechi GP, Zuddas M, Piredda M, Agnetti V, Sau G, Piras ML, Tanca S, Rosati G (1989). "Treatment of cerebellar tremors with carbamazepine: a controlled trial with long-term follow-up". Neurology. 39 (8): 1113–5. PMID 2668787.
  86. ↑ Information from the USA National library of medicine on propanolol[8]
  87. ↑ Aisen ML, Holzer M, Rosen M, Dietz M, McDowell F (1991). "Glutethimide treatment of disabling action tremor in patients with multiple sclerosis and traumatic brain injury". Arch. Neurol. 48 (5): 513–5. PMID 2021365.
  88. ↑ 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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