Description

• A chronic disease involving inflammation and degeneration leading to demyelinization of the white matter of the brain and spinal cord with axonal damage (1):
• 4 internationally recognized forms:
  • Relapsing/remitting multiple sclerosis (RRMS) (85%): Periods of relapse during which time new symptoms can appear and previous symptoms worsen followed by periods of remission. Can result in residual deficits or full recovery between symptomatic periods.
  • Secondary progressive MS (SPMS): Steady progression of clinical neurologic damage with or without relapses and minor remissions. Of patients with RRMS, 50% will develop SPMS; patients may have experienced RRMS for ≥2–40 years. Relapses and remissions will frequently decrease over time.
  • Primary progressive MS (PPMS): Gradual progression of the disease from onset with no relapses or remissions.
  • Progressive relapsing MS (PRMS) (least common): Steady, cumulative progression of clinical neurologic damage with superimposed relapses and remissions.
• Clinically isolated syndromes (CIS): Initial clinical manifestation of demyelination; most commonly consisting of optic neuritis, transverse myelitis, and brain stem syndromes

• Relapses are less frequent during pregnancy, especially in the 3rd trimester, as well as in the postpartum period.
• Pregnancy does not alter the overall course of MS.
• Relapse rate is unaffected by breastfeeding

Epidemiology

• Predominant age: 20–40 years. Exception: PRMS is typically diagnosed in patients >40 years of age.
• Predominant sex: Female > Male. Males experience a more malignant course than females.

Incidence
3.6 cases/100,000 person-years in women and 2.0 cases/100,000 person-years in men worldwide (2).

Prevalence
In the US, 400,000 people have MS; 2.5 million cases worldwide

Risk Factors

• Northern European descent
• Family history of the disease; 1–3% risk of MS among 1st-degree relatives (3)
• Temperate climate: Higher latitude was previously associated with a higher MS incidence; however, studies after 1980 have shown an increased incidence of MS at lower altitudes, closer to the equator (2). Migration from high-risk to low-risk areas before puberty protects against acquiring MS (3).

• Hereditary predisposition: HLA-DRB1
• Patients with MS are more likely to have other autoimmune disorders.

General Prevention

No known preventive measures.

Pathophysiology

• Neurodegeneration within plaques leads to disability; disease is radiologically active during periods of apparent clinical stability.
• Disease occurs in genetically susceptible people with breaches in the blood–brain barrier (BBB); invasion of autoreactive T cells (primarily Th-1) and intrathecal B cells damage the CNS.
• Histological findings: Perivascular infiltration of leukocytes, parenchymal edema, loss of myelin and oligodendrocytes, widespread axonal damage, plasma cells, myelin-filled macrophages, hypertrophic astrocytes

Etiology

Unknown but various theories:

• Autoimmune theory: HLA linkage, hereditary pattern, immunocytes in plaques, changes in peripheral blood immunocytes
• Low vitamin D levels and limited sun exposure
• Combined theory: Autoimmune disorder triggered in genetically susceptible individuals as an infrequent response to environmental factors
• Viral or infective hypothesis: Epstein-Barr virus, human herpes virus 6, MS-related human endogenous retroviruses, and Chlamydophila pneumoniae (3)

Commonly Associated Conditions

• Optic neuritis: Unilateral eye pain, worse with movements: Scotoma (loss of mainly central vision); color desaturation; Marcus Gunn pupil (afferent pupillary defect)
• Internuclear ophthalmoplegia (INO): Horizontal nystagmus of abducting eye: Lost/delayed adduction
• Lhermitte phenomenon: Shocklike sensation with head and/or neck movement