Diagnosis and Treatment of Multiple Sclerosis

Abstract

ultiple sclerosis (MS) is an autoimmune central nervous system (CNS) disorder characterized by inflammatory demyelination and axonal transection, defined as severed terminal axonal structures representing the pathological correlate of irreversible neurologic damage. MS affects approximately 900 000 people in the US. [1][2][3] MS is typically diagnosed in adults aged 20 to 30 years and often affects physical functioning, cognition, quality of life, and employment. The cause of MS is unclear, but many genetic (eg, major histocompatibility complex HLA-DRB1 locus) and environmental factors, such as vitamin D levels (increased risk at levels <100 nmol/L [40 ng/mL; reference range, 40-60 ng/mL]), ambient UV radiation, Epstein-Barr virus infection, and tobacco smoking, are associated with MS. [4][5][6][7][8][9] Current treatment for MS consists of a multidisciplinary approach including disease-modifying therapies (DMTs), symptomatic treatment, lifestyle modifications, psychological support, and rehabilitation interventions. The first DMT, interferon beta-1b, was approved by the US Food and Drug Administration (FDA) in 1993. As of July 2020 there were 9 classes of DMTs approved for the treatment of MS (interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate [S1P] receptor modulators, fumarates, cladribine, natalizumab, ocrelizumab, alemtuzumab). 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 interfe...

Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon Beta-1a (Avonex)

“…Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) of unknown etiology with a projected 2020 prevalence of > 0.9 million cases in the United States [ 1 ] and an estimated 2020 global prevalence of > 2.8 million cases [ 2 ]. Symptoms of MS usually appear in adults between 20 and 50 years of age [ 3 – 5 ] and may include fatigue, visual impairment, motor weakness, ataxia, reduced mobility, tremor, sensory loss, pain, impaired genitourinary function, depression, and cognitive impairment [ 6 ]. These symptoms have a negative impact on patients’ quality of life (QoL) by interfering with gainful employment, interpersonal relationships, intimate and leisure activities, and other daily activities [ 7 , 8 ].…”

Crosstalk between Interleukin-1β and Type I Interferons Signaling in Autoinflammatory Diseases

“…Whilst interferonopathies and inflammasomopathies may appear as very divergent or even antagonistic inflammatory diseases (although an overlap can be observed in some instances, as mentioned in the previous chapters), the pathogenesis of some inflammatory conditions clearly involves both type I IFNs and IL-1β. Multiple sclerosis (MS) belongs to this category, since IL-1β is strongly implicated in this inflammatory, neurodegenerative disease [ 38 ], and IFN-β is still a classical first-line therapy [ 39 ], although rituximab (an anti-CD20 monoclonal antibody designed to induce B cell ablation) was shown recently as a promising option [ 40 ]. Low STING-dependent type I IFNs expression in peripheral blood mononuclear cells (PBMC) isolated from MS patients [ 41 ] is in agreement with these observations.…”

Approach to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis

“…Fortunately, several different types of immunomodulatory and immunosuppressive therapies have become available over the last decades. Application of these disease-modifying therapies (DMT) significantly reduces relapse frequency but some DMT are also associated with a higher susceptibility to infections (21)(22)(23). While MS patients do not have an increased risk of SARS-CoV-2 infection or severe COVID-19 disease per se, the risk is elevated in the presence of comorbidities, higher age, greater MS-associated disability, progressive MS disease course, and under treatment with some types of DMT (24)(25)(26)(27)(28).…”