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Diagnosis and Treatment of Multiple SclerosisA Review

Educational Objective
To review the clinical management of patients with multiple sclerosis.
1 Credit CME

Importance  Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS.

Observations  MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging [MRI] T2 lesions), and laboratory findings (eg, cerebrospinal fluid–specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease.

Conclusions and Relevance  MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.

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Article Information

Corresponding Author: Alexander D. Rae-Grant, MD, 10 Estes St, Ipswich, MA 01938 (raegranta@gmail.com).

Accepted for Publication: December 28, 2020.

Correction: This article was corrected on June 1, 2021, for incorrect or incomplete data in Table 3.

Author Contributions: Dr Rae-Grant had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Goldschmidt, Rae-Grant.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: McGinley, Rae-Grant.

Administrative, technical, or material support: McGinley.

Supervision: McGinley, Rae-Grant.

Conflict of Interest Disclosures: Dr McGinley reported serving on scientific advisory boards for Genzyme and Genentech; receiving research support from Novartis; and receiving funding from a KL2 (KL2TR002547) grant from Clinical and Translational Science Collaborative of Cleveland, from the National Center for Advancing Translational Sciences component of the National Institutes of Health. Dr Rae-Grant reported serving as chair of the American Academy of Neurology guideline subcommittee; that he was lead author on the subcommittee’s 2018 guideline on disease-modifying therapy for multiple sclerosis; and working part time as deputy editor for Ebsco industries editing neurology, psychiatry, and palliative care content in Dynamed, a subscription-based online point-of-care tool for clinicians. None of these activities are supported by the pharmaceutical or device industry. No other disclosures were reported.

Additional Contributions: We would like to acknowledge Cleveland Clinic illustrator Amanda Mendelsohn, BS, BFA, for preparing a draft of the figure. Ms Mendelsohn was not compensated for her contributions.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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