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Upon completion of the chapter, the reader will be able to:

  1. Identify risk factors for multiple sclerosis (MS).

  2. Describe pathophysiologic findings of MS.

  3. Distinguish between forms of MS based on patient presentation and disease course.

  4. Compare and contrast MS disease-modifying treatment choices for a given patient.

  5. Determine appropriate symptomatic treatment choices for a given patient.

  6. Develop a monitoring plan for a patient placed on specific medications.


Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), variable in symptoms and presentation. Multiple describes the number of CNS lesions, and sclerosis refers to the demyelinated lesions, today called plaques.



Approximately 2.3 million people worldwide have MS.1 Diagnosis usually occurs between 20 and 50 years, affecting twice as many women as men.1 Whites and people of northern European heritage are more likely to develop MS; prevalence decreases with decrease in latitude.1,2 Risk factors include family history of MS, autoimmune diseases, or migraine; personal history of autoimmune diseases or migraine; and, in women, cigarette smoke exposure.


Inheritance Theory

Family members of MS patients have a 5% risk; monozygotic twins have a concordance rate of 25% to 30%.2 Genetics cannot fully explain the etiology of MS because only a small proportion of patients report a family member with MS; however, genetic risks may explain up to 35% of cases.3

Environment Theory

Epstein-Barr virus is thought to be a possible infectious etiologic agent.3 Infection cannot fully explain MS because there is a high rate of seropositivity in the population, but MS is much less common. Other environmental theories involve decreased patient or maternal vitamin D serum concentrations or high sodium consumption.2,3


While the causative agent of MS is unclear, the result is the development of an autoimmune disorder with areas of CNS inflammation and degeneration.


An unknown antigen presented by the major histocompatibility complex (MHC) class II molecules causes T-cells to become autoreactive (Figure 30–1). Autoreactive T-cells enter lymphatic tissues to expand. Upon a signal involving sphingosine-1-phosphate, T-cells reenter the circulation.4 Once activated, T-cells attach to upregulated adhesion molecules and produce matrix metalloproteinases (MMP) that cause blood–brain barrier breakdown. In the CNS, T-cells come into contact with antigen-presenting cells and proliferate. The T-helper cells differentiate into proinflammatory T-helper-1 cells (Th1 cells) and anti-inflammatory T-helper-2 cells (Th2 cells).4 Th1 cells secrete cytokines that enhance macrophage and microglial cells that attack myelin.4

FIGURE 30–1.

Autoimmune theory of the pathogenesis of MS. In MS, the immunogenic cells tend to be more myelin-reactive, and these T-cells produce cytokines ...

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