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Multiple Sclerosis: Overview and Risk Factors

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). The pathological process involves white–matter inflammation in many areas of the CNS, along with demyelination, oligodendrocyte loss, glial scarring, and eventual axonal destruction. MS may shorten life span by 10 or more years, compared with national averages. The disease may present in several ways. The most common form is relapsing–remitting, often with incomplete remission and some accumulating disability. It may be progressive from the outset (primary progressive) or may later become progressive after a period of relapses and remissions (secondarily progressive). However, in a small minority of patients, the disease is benign with no or little evidence of accumulating disability.

It remains to be determined whether primary progressive MS has the same pathophysiology as the more common types.

Typical age of MS onset is the mid–to–late 20s for the relapsing–remitting type, and mid–to–late 30s for the primary–progressive type (although the age range is large). Persons with relapsing–remitting MS can convert to progressive MS, typically in their early 40s. The age of peak onset is 5 years earlier for women than for men, and women with MS typically outnumber men by 2 to 3 times.1,2

Symptoms and signs of the disease depend upon the part of the central nervous system affected. MRI studies show that most lesions are asymptomatic although the effect of lesions may be cumulative and the condition of some patients rapidly deteriorates.

Presenting symptoms in descending order of frequency are:

  • Sensory change in extremities.
  • Optic neuritis.
  • Motor symptoms including weakness, spasm, and paraplegia.
  • Diplopia or internuclear ophthalmoplegia.
  • Gait difficulties.
  • Bladder/bowel dysfunction, vertigo, or pain.

Other vague symptoms, such as fatigue or cognitive difficulty may become prominent with time and may correlate with the pathological progression.

Risk Factors

No exact list of risk factors has been identified for MS. However, the following demographic and other factors are relevant:

Race and ethnicity. Risk varies dramatically among racial and ethnic groups. Among affected individuals, whites outnumber blacks by a 9:1 ratio. The condition is particularly common among Palestinians, Parsis, and Sardinians, and rare among Chinese and Japanese individuals, African blacks, and certain other ethnic groups.3

Geography. Risk depends on place of residence during the prepubertal years, increasing with distance from the equator. However, this finding may represent genetic susceptibility or vitamin D activity.

Vitamin D. Supplementation of vitamin D is associated with reduced risk.4,5

Smoking. Smoking increases risk.6

Heredity. Monozygotic twins have a 20% to 39% risk when one twin has MS, as compared with a 3% to 5% risk in nontwin siblings or dizygotic twins.7 Maternal origin of a hereditary factor is suggested.8

Chlamydia pneumonia. This illness is associated with progressive MS.9

Viruses. MS is associated with viruses, especially Epstein Barr virus, but no definitive causal link to any particular virus has been established as yet.10

Vaccines. The role, if any, of vaccines as risk factors for MS has been controversial, and evidence for such a link is weak. For persons who have MS, vaccines are believed to be safe.11,12

Stress. Stressful life events have been found to be associated with exacerbations of MS.13,14


Multiple Sclerosis: Diagnosis >>