Exam 50: Epidemiology of Multiple Sclerosis

Correct Answer:

Verified

Multiple sclerosis is characterized by disruptions in the blood-brain barrier, inflammatory gliosis, and demyelination and death of neurons.
Disruption of the blood-brain barrier has been found to precede the development of multiple sclerosis. The blood-brain barrier consists of tight junctions between the endothelial cells that line the capillaries and other blood vessels of the brain and spinal cord. Under normal conditions, these tight junctions prevent entrance of T cells into neurological tissues; however, many viruses and certain other infectious agents may compromise the blood-brain barrier and allow T cells to pass through. Upon clearance of the infection, the T cells are trapped inside the brain and may stimulate immunoreactivity and inflammation. Notably, dysregulation of the blood-brain barrier and transendothelial migration of activated leukocytes and their release of inflammatory cytokines and chemokines are among the earliest cerebrovascular abnormalities seen in multiple sclerosis brains.
Inflammation is a chief pathologic hallmark of relapsing-remitting multiple sclerosis. According to one model, T cells gain entrance into the brain through the blood-brain barrier and become immunoreactive, thereby stimulating a cascade of destructive inflammatory processes including axon transection, myelin degradation, and glial cell death.
Localized foci of demyelination are present in white and gray matter in the brains of multiple sclerosis patients. Imaging these lesions using MRI with gadolinium enhancement provides the most conclusive evidence for a diagnosis of relapsing-remitting multiple sclerosis. Lesions can be pathologically characterized as immunologically active or chronic by various degrees of microgliosis, astrocytosis, myelin vacuolation or loss, and axonal transection. Demyelinated lesions will undergo a reparative process whereby oligodendrocytes replace lost myelin with a thinner but still functional sheath. These repaired lesions are called shadow lesions and are of intense interest because they exhibit a natural mechanism whereby the brain replaces lost myelin.
Failure of remyelination by oligodendrocytes is thought to be largely responsible for sustained neurological symptoms in patients with progressive multiple sclerosis.
Axonal destruction appears early and accumulates with disease progression. Progressive multiple sclerosis fails to respond to current immunomodulatory therapies.