Diagnosis and Treatment of Multiple Sclerosis: A Review
Abstract
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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Patients receiving MS therapies were at risk of additional adverse events including flu-like symptoms, hepatotoxicity, autoimmune complications, recurrent infections, and in rare cases progressive multifocal leukoencephalopathy.
“Patients were also at risk of additional adverse events from these therapies, including flu-like symptoms, hepatotoxicity, autoimmune complications, recurrent infections, and in rare cases, progressive multifocal leukoencephalopathy.10,12,13”
From Multiple Sclerosis Misdiagnosis in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (2026) · cites this paper as [10]
Prominent microbleeds favor a small vessel disease diagnosis rather than MS.
“Furthermore, a high CMB burden (>10) and region-specific CMB distribution were observed only in correctly diagnosed patients, suggesting that prominent microbleeds favor a small vessel disease diagnosis rather than MS.1,4,10”
From Multiple Sclerosis Misdiagnosis in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (2026) · cites this paper as [10]
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- Authors
- McGinley, M. P., Goldschmidt, C. H., & Rae-Grant, A. D.
- Affiliations
- Cleveland Clinic (US)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2021-02-23
- Volume
- 325
- Issue
- 8
- Pages
- 765
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W3131957723
- Cited by
- 1,205
- References
- 7
- Citations by year
- 2026: 228 · 2025: 248 · 2024: 305 · 2023: 225 · 2022: 141 · 2021: 58
- FWCI
- 31.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- multiple sclerosis, diagnosis, disease-modifying therapy, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, primary progressive multiple sclerosis, McDonald criteria, oligoclonal bands, interferon, glatiramer acetate, teriflunomide, sphingosine-1-phosphate receptor modulator, fumarate, cladribine, ocrelizumab, monoclonal antibodies, adverse effects, autoimmune thyroid disease
- MeSH terms
- Central Nervous System, Cognition Disorders, Fatigue, Female, Humans, Immunosuppressive Agents, Magnetic Resonance Imaging, Multiple Sclerosis, Pregnancy, Quality of Life, Disease Progression
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