Description

Subtypes of MS (1):

• Clinically isolated syndrome (CIS): Patient’s initial symptoms are characteristic of CNS demyelination that may be due to MS but does not fulfill the criteria of dissemination in time; ~80% of patients with CIS will later relapse and be diagnosed with MS.
• Radiologically isolated syndrome (RIS): incidental brain or spinal cord MRI findings highly suggestive of MS in an asymptomatic patient; no evidence of clinical attacks suggestive of MS; ~30–40% of patients with RIS later meet criteria for CIS or MS.
• Relapsing-remitting MS (RRMS): most common type of disease onset; defined by relapse (attacks or exacerbations) followed by partial or complete improvement; recovery of residual deficits may ensue following each episode.
• Secondary progressive MS (SPMS): progressive worsening of neurologic function following initial RRMS; may be associated with acute exacerbations; often diagnosed retrospectively
• Primary progressive MS (PPMS): progressive decline in disease status and accumulation of disability from onset of disease without initial relapsing-remitting disease course (~10% of patients) (2)

Pregnancy Considerations

• If treatment is clinically necessary during pregnancy, preferred treatments include interferon-β and glatiramer acetate (3).
• Natalizumab may be continued with reduced infusion regimen for patients with high risk of relapse (3).
• Majority of patients experience reduced disease exacerbations during pregnancy but relapse in the postpartum period.
• All drugs licensed for MS treatment are contraindicated during breastfeeding.

Epidemiology

Most often affects Caucasian women during their 2nd and 3rd generations of life.

Incidence
2.1 per 100,000 person-years (1)

Prevalence

• Differs by latitude, higher rates among those living further from the equator (1)
• America: 117.49 per 100,000 people
• Worldwide: 43.95 per 100,000 people

Etiology and Pathophysiology

• Predominately an autoimmune process driven by T cells and B cells against the myelin sheath. Dysregulation and mistaken antigen identity lead CD4 T cells to cross the blood–brain barrier and recognize proteins on the surface of the myelin sheath. Cytokines, interferon-γ, and tumor necrosis factor-α are subsequently released, and activation of macrophages and B cells leads to oligodendrocyte and myelin destruction, resulting in slower saltatory nerve conduction velocities.
• Oligodendrocytes, which have survived or formed from precursor cells, are able to partially remyelinate stripped axons, producing scars which overtime can lead to irreversible axonal loss and brain atrophy.
• The majority of axons are typically lost from the lateral corticospinal (motor) tracts of the spinal cord (2).

Genetics
Over 100 genetic loci have been associated with MS, suggesting that it is ultimately an antigen-specific autoimmune process. Most commonly, these are mapped to the class II region of the HLA gene clusters. The most common is the HLA-DRB1 locus on chromosome 6, which produces major histocompatibility complexes with high-binding affinity for myelin basic proteins.

Risk Factors

• Age: peak incidence ages 20 to 40 years, but can present at any age (slightly earlier in women than men)
• Sex: female > male
• Race: Caucasian > Afro-Caribbean > East Asian
• Prior infections: Epstein-Barr virus; mononucleosis
• Substance: tobacco smoking
• Historically, proximity to the equator and its correlation with increased vitamin D exposure were inversely proportional to MS incidence. However, this association has been less noted and may be due to lifestyle changes leading to decreased sun exposure in these areas (2).
• Anti-TNF-α inhibitors like etanercept and infliximab have been associated with developing MS.

Commonly Associated Conditions

Internuclear ophthalmoplegia, optic neuritis, transverse myelitis, association with other autoimmune processes