Multiple Sclerosis: Pathogenesis, Symptoms, and Treatment

Introduction

Multiple sclerosis is an autoimmune disease caused by activated T cells that gain entry into the central nervous system. The injury results from inflammation and T cell destruction. There are typical symptoms that correlate with the area involved, along with remissions and relapses that can be triggered by certain factors. Diagnosis of the disease requires visualization of lesions in the central white matter on an MRI. Treatment is based on immunosuppressants and steroids to combat inflammation.

Pathogenesis

"Multiple sclerosis is an acute inflammatory disease that causes focal demyelination of the brain and spinal cord; it also causes axonal loss." (Poser, 2011)

In multiple sclerosis, activated T lymphocytes enter through the blood-brain barrier and initiate central nervous system inflammation by recognizing myelin-derived antigens as foreign on the surface of the central nervous system's antigen-presenting cells, the microglia. The resulting inflammation releases cytokines, which initiate destruction of the oligodendrocyte-myelin unit by macrophages.

Morphologically, the affected regions show multiple, well-circumscribed, slightly depressed, glassy, gray-tan, irregularly shaped lesions termed plaques. These characteristic lesions are inflammatory demyelinations that occur most commonly in the periventricular region, the optic nerves and chiasms, ascending and descending fiber tracts, the cerebellum, and the spinal cord. Initially, there is an accumulation of activated T lymphocytes and macrophages, often with prominent perivascular inflammation. After an acute attack, gliosis follows, leaving a shrunken gray scar.

The initial acute clinical signs and symptoms are due to the effects of inflammatory cytokines upon transmission of nervous impulses, and not due to the breakdown of myelin. This, along with the role of corticosteroids, may explain why recovery from acute deficits is prompt. However, when there is breakdown of myelin resulting from an acute attack, it affects the propagation of impulses or causes a complete block in conduction, lowering the efficiency of central nervous system functions. Moreover, acute inflammatory mediators, such as nitric oxide, also initiate axonal damage, which is a feature of the later stages of the disease.

In acute attacks of established multiple sclerosis, there is progressive axonal loss, possibly because of direct damage caused by inflammatory mediators and the subsequent loss of neurotrophic factors from oligodendrocytes. This axonal loss is responsible for the phase of the disease in which the patient becomes permanently and progressively disabled.

Etiology and Prevalence

The etiology of multiple sclerosis involves the role of both genetic and environmental factors. The disease is more likely to occur in northern Europeans and less common among other racial groups, decreasing in frequency in regions nearer to the equator. The lifetime risk of multiple sclerosis in northern Europe is one in eight hundred, increasing to one in fifty, one in twenty, and one in three for the offspring, siblings, and monozygotic twin partners of affected individuals, respectively. In other areas, such as New Zealand, Spain, and Africa, the disease occurs more frequently in those of Caucasian descent. (D.A, 1996)

Other than the already established candidate genes (DRB1.1501, DRB5.0101, DQA1.0102, and DQV2.0602), preliminary evidence also associates CD24 with multiple sclerosis as a factor modifying disease progression. These genes are not causative factors but play a role in modifying an individual's susceptibility to multiple sclerosis. (D.A, 1996)