Skip to Main Content

LEARNING OBJECTIVES

LEARNING OBJECTIVES

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

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

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

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

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

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

INTRODUCTION

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

EPIDEMIOLOGY AND ETIOLOGY

Epidemiology

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

Etiology

The cause of MS is unknown, but may be genetic, environmental, or both. Genetic risks may explain up to 35% of cases.2 Environmental theories involve infectious agents or decreased patient or maternal vitamin D serum concentrations or other infectious exposures.2,3

PATHOPHYSIOLOGY

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

Inflammation

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 cause blood–brain barrier breakdown and enter the CNS. These T-cells come into contact with antigen-presenting cells (APCs) and proliferate and differentiate. Th1 cells secrete cytokines that enhance macrophage and microglial cells that attack myelin.4

FIGURE 30–1.

Autoimmune theory of the pathogenesis of multiple sclerosis (MS). In MS, the immunogenic cells tend to be more myelin-reactive, and these T-cells produce cytokines mimicking a Th1-mediated proinflammatory reaction. T-helper cells (CD4+) appear to be key initiators of myelin destruction in MS. These autoreactive CD4+ cells, especially of the T-helper cell type 1 (Th1) subtype, are activated in the periphery, perhaps following a viral infection. The activation of T- and B-cells requires two signals. The first signal is the interaction between MHC and APC (macrophage, dendritic cell, and B-cell). The second signal consists of the binding between B7 on the APC and CD28 on the T-cell for T-cell activation. Similarly, CD40 expressed on APCs and CD40L expressed on T-cells interact to signal the proliferation of B-cells within the blood–brain barrier following the entry to T-cells. The ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.