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Multiple Sclerosis (MS)

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Treatment

Multiple sclerosis (MS) patients typically present a combination of symptoms that include impaired motor control, fatigue, spasticity, impaired balance, pain, bladder and bowel issues, neurological changes (such as vertigo), and cognitive and sexual dysfunctions.1

As there is no cure available for MS, treatment approaches for this disease fit into 2 distinct groups: one focused on managing the immune-related aspects of the disease and a second focused on the control and relief of symptoms.2 The main goal of these treatment options is to allow patients to live a normal life as much as possible. Treating MS patients requires a multidisciplinary team of physicians capable of addressing this large range of clinical manifestations.

Treatment of Emergency and Acute Relapses in MS

Situations requiring emergency treatment rely on the intravenous administration of immunoglobulins (IVIG) and steroids or the performance of plasmapheresis.3,4 Options for controlling acute relapses manifested by brain and spinal cord inflammation include the use of methylprednisolone or prednisone.5 

There are additional options for patients who are intolerant to treatment with corticosteroids, which include a repository corticotropin injection.5 Despite alleviating symptoms, plasmapheresis is generally recommended for relapsing attacks that are refractory to corticosteroids administration.6

Immunomodulatory Therapy

Interferons, sphingosine 1-phosphate (S1P) receptor modulators, monoclonal antibodies, and other immune modulators, such as glatiramer acetate, mitoxantrone, and teriflunomide7 are disease-modifying agents that help in reducing both severity and frequency of attacks.2 These agents are also capable of slowing down MS progression and the formation of central nervous system (CNS) lesions.2 Their administration routes include oral, intramuscular, and intravenous.7

To date, ocrelizumab is the only therapeutic agent approved for treating primary progressive multiple sclerosis (PPMS).8,9 The potential use of interferon 1b for application in PPMS has also been the subject of study,10 however, limited data is available.11 

Treatment of Aggressive MS

Aggressive manifestations of MS can be stabilized by the administration of high doses of cyclophosphamide.12 The combination of cyclophosphamide with glatiramer acetate has been proven to slow down disease progression and the risk of relapse.13 

Mitoxantrone can be an option for patients with secondary progressive, progressive relapsing, or worsening relapsing-remitting MS.14 However, the use of this immunosuppressive agent is correlated with increased risk of cardiac events, as well as a risk of developing acute myeloid leukemia (AML) as a secondary cancer.15

Stem Cell Transplantation

Stem cell therapy for MS treatment has been the subject of recent studies and clinical trials.16,17 These studies need, however, to gather more information that can support the implementation of this procedure in the clinics.

Treating MS During Pregnancy

Women diagnosed with MS can have normal pregnancies, however, as more research is needed to understand and support MS treatment during pregnancy, each case should be analyzed individually, considering the potential risks involved for the fetus and the potential risks of relapses for the patients.

Pregnancy can act as a natural modifier of the disease, reducing the event of relapses during the third trimester in about 70% of cases.18 Drugs that have teratogenic potential such as teriflunomide must not be prescribed. The same rationale must be followed for drugs that may induce rebound relapses (fingolimod, natalizumab) and for which the risks are unclear (dimethyl fumarate and alemtuzumab). 

Different recent studies point to a potential reduction in relapse risk in women who are breastfeeding.19,20 Treatment regimens that prescribe glatiramer acetate, interferon beta, natalizumab, and rituximab/ocrelizumab may be resumed if necessary.21

Managing Symptoms

One of the most common symptoms of MS is fatigue, which can affect about 92% of patients.22,23 Managing fatigue involves monitoring and alternating periods of rest and exercise. Amantadine can also be administered. However, there are no US Food and Drug Administration (FDA) approved drugs indicated for MS that alleviate fatigue.24 

Pain is also a common symptom, with origination in the demyelinating process but also resulting from the spasticity that leads to poor postures and impairs the musculoskeletal system. Pain can be managed by the administration of tricyclic antidepressants as first-line treatment and by anticonvulsant agents such as carbamazepine or gabapentin. Painkillers can also alleviate non-neuropathic pain.25.

Spasticity should be ameliorated to allow patients to experience less pain and to provide them with more mobility. Drugs used to manage this condition include baclofen, benzodiazepines such as diazepam and clonazepam, dantrolene sodium, and gabapentin.26 Balance is also typically compromised in MS patients. Dalfampridine is an FDA-approved drug that can be used for improving patients’ walking ability.27

Bladder and bowel issues are typical problems experienced by MS patients. Symptoms include urgency, frequency, nocturia, incontinence, urinary tract infections, and constipation. Pharmacological options include the use of anticholinergic medication (oxybutynin),28 stool softeners, or laxatives.

Other conditions such as depression and sexual dysfunction are not uncommon in MS patients and appear to be related. Depression can be managed with selective serotonin reuptake inhibitors and other antidepressants, while erectile dysfunction treatment usually performed with oral phosphodiesterase type 5 (PDE-5) inhibitors such as sildenafil, tadalafil, or vardenafil.29

Rehabilitation

Physical, occupational, and speech therapy programs may help patients to lead their lives with improved quality by restoring or improving several basic functions.

Physical therapy enables patients to decrease spasticity and improve mobility and coordination through specific strength-building and stretching programs.30 Transcutaneous electrical nerve stimulation (TENS) can be also used. Different support and mechanical aids can be provided to assist patients’ mobility.

Occupational therapy has also an important role in MS patients’ lives. Specialists assess and follow patients’ abilities in performing daily routines and help them adapt to changes during the disease course. These adaptations may include the use of adaptive equipment. Compensatory techniques are also worked with these patients to treat cognitive dysfunctions and improve memory.5

Speech therapy helps patients to work through speech and swallowing issues.

Surgery for Symptom Management

Surgery in MS patients is focused on treating severe spasticity and pain. These procedures should be evaluated on a case-to-case basis and can include the placement of intrathecal pumps that allow the administration of antispasticity drugs. These neurosurgical techniques may improve patients’ symptoms and consequently quality of life.31

References

1. Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet. 2018;391(10130):1622-1636. doi:10.1016/S0140-6736(18)30481-1

2. Hauser SL, Cree BAC. Treatment of multiple sclerosis: a review. Am J Med. 2020;133(12):1380-1390.e2. doi:10.1016/j.amjmed.2020.05.049

3. Sorensen PS. The role of intravenous immunoglobulin in the treatment of multiple sclerosis. J Neurol Sci. 206(2):123-130. doi:10.1016/s0022-510x(02)00343-x

4. Rodriguez M, Karnes WE, Bartleson JD et al. Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology 43(6):1100-1104. doi:10.1212/wnl.43.6.1100

5. Managing relapses. National Multiple Sclerosis Society. Accessed June 11, 2021.

6. Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 76(3):294-300. doi:10.1212/WNL.0b013e318207b1f6

7. Medications. National Multiple Sclerosis Society. Accessed June 11, 2021.

8. FDA approves new drug to treat multiple sclerosis. News release. US Food and Drug Administration. April 25, 2021.

9. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209-220. doi:10.1056/NEJMoa1606468

10. Tur C, Montalban X, Tintoré M, et al. Interferon β-1b for the treatment of primary progressive multiple sclerosis: five-year clinical trial follow-up. Arch Neurol. 2011;68(11):1421-1427. doi:10.1001/archneurol.2011.241

11. Rojas JI, Romano M, Ciapponi A, Patrucco L, Cristiano E. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev. Published online January 20, 2010. doi:10.1002/14651858.CD006643.pub3 

12. Awad, A, Stuve O. Cyclophosphamide in multiple sclerosis: scientific rationale, history and novel treatment paradigms. Ther Adv Neurol Disord. 2009;2(6):50-61. doi:10.1177/1756285609344375

13. Harrison DM, Gladstone DE, Hammond E, et al. Treatment of relapsing-remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance. Mult Scler. 2012;18(2):202-209. doi:10.1177/1352458511419701

14. Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G. Mitoxantrone for multiple sclerosis. Cochrane Database Syst Rev. Published online May 31, 2013. doi:10.1002/14651858.CD002127.pub3

15. Novantrone Label. US Food and Drug Administration. Accessed June 12, 2021.

16. Cuascut FX, Hutton GJ. Stem cell-based therapies for multiple sclerosis: current perspectives. Biomedicines. Published online March 30, 2019. doi:10.3390/biomedicines7020026

17. Muraro PA, Pasquini M, Atkins HL, et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol. 2017;74(4):459-469. doi:10.1001/jamaneurol.2016.5867

18. Voskuhl R, Momtazee C. Pregnancy: effect on multiple sclerosis, treatment considerations, and breastfeeding. Neurotherapeutics. 2017;14(4):974-984. doi:10.1007/s13311-017-0562-7

19. Langer-Gould A, Smith JB, Albers KB et al. Pregnancy-related relapses and breastfeeding in a contemporary multiple sclerosis cohort. Neurology. 2020;94(18):e1939-e1949. doi:10.1212/WNL.0000000000009374

20. Krysko KM, Rutatangwa A, Graves J et al. Association between breastfeeding and postpartum multiple sclerosis relapses: a systematic review and meta-analysis. JAMA Neurol. 2020;77(3):327-338. doi:10.1001/jamaneurol.2019.4173  

21. Langer-Gould AM. Pregnancy and family planning in multiple sclerosis. Continuum (Minneap Minn). 2019;25(3):773-792. doi:10.1212/CON.0000000000000745

22. Manjaly ZM, Harrison NA, Critchley HD, et al. Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(6):642-651. doi:10.1136/jnnp-2018-320050

23. Attarian HP, Brown KM, Duntley SP, Carter JD, Cross AH. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch Neurol. 2004;61(4):525-528. doi:10.1001/archneur.61.4.525

24. Fatigue.  National Multiple Sclerosis Society. Accessed April 25, 2021.

25. Pain.  Multiple Sclerosis Society. Accessed April 25, 2021.

26. Beard S, Hunn A, Wight J. Treatments for spasticity and pain in multiple sclerosis: a systematic review. Health Technol Assess. 2003;7(40):iii-111. doi:10.3310/hta7400

27. Walking-gait-balance-coordination. Multiple Sclerosis Society. Accessed April 25, 2021.

28. Nicholas RS, Friede T, Hollis S, Young CA. Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database Syst Rev. Published online January 21, 2009. doi:10.1002/14651858.CD004193.pub2 

29. Landtblom AM. Treatment of erectile dysfunction in multiple sclerosis. Expert Rev Neurother. 2006;6(6):931-935. doi:10.1586/14737175.6.6.931

30. Kubsik-Gidlewska AM, Klimkiewicz P, Klimkiewicz R, Janczewska K, Woldańska-Okońska M. Rehabilitation in multiple sclerosis. Adv Clin Exp Med. 2017;26(4):709-715. doi:10.17219/acem/6232931.

31. Patwardhan RV, Minagar A, Kelley RE, Nanda A. Neurosurgical treatment of multiple sclerosis. Neurol Res. 2016;28(3):320-325. doi:10.1179/016164106X98224

Reviewed by Kyle Habet, MD, on 7/1/2021.

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