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A number of viruses share the unique tendency to primarily affect the human nervous system. Included in this group are the human immunodeficiency viruses (HIV-1 and HIV-2), herpes simplex viruses (HSV-1 and HSV-2), herpes zoster or varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), poliovirus, rabies, and several seasonal arthropod-borne viruses (Flaviviruses). Some of these are neurotropic, exhibiting an affinity for certain types of neurons: for example, poliomyelitis viruses and motor neurons, VZV and peripheral sensory neurons, and rabies virus and brainstem neurons. Yet others attack nonneuronal supporting cells; JC virus causing progressive multifocal leukoencephalopathy is the prime example. For many of the rest, the affinity is less selective in that all elements of the nervous system are involved. Herpes simplex, for example, may devastate the medial parts of the temporal lobes, destroying neurons, glia cells, myelinated nerve fibers, and blood vessels; and HIV, the cause of AIDS, may induce multiple foci of tissue necrosis throughout the cerebrum.

These relationships and many others, which are the subject matter of this chapter, are of wide interest in medicine. In some conditions, the systemic effects of the viral infection are negligible; it is the neurologic disorder that brings them to medical attention. In other words, the neural aspects of viral infection are disproportionate to the systemic illnesses. This aspect of neurology must therefore also be familiar to pediatricians and internists, who are likely to be the first to see such patients.

A detailed discussion of viral morphology and cell–virus interactions is beyond the scope of a textbook about neurology. Authoritative overviews of this subject can be found in the introductory chapters of R.T. Johnson’s monograph Viral Infections of the Nervous System.

Pathways of Infection

Viruses gain entrance to the body by one of several pathways. Mumps, measles, and VZV enter via the respiratory passages. Polioviruses and other enteroviruses enter by the oral–intestinal route, and HSV enters mainly via the oral or genital mucosal route. Other viruses are acquired by inoculation, as a result of the bites of animals (e.g., rabies) or mosquitoes (arthropod-borne or arbovirus infections). The fetus may be infected transplacentally by rubella virus, CMV, and HIV.

Following entry into the body, the virus multiplies locally and in secondary sites and usually gives rise to a viremia. Most viruses are prevented from entering central nervous system (CNS) tissues, presumably by the blood–brain barrier. Moreover, most antibodies and immunocompetent cells are excluded from the CNS as well, so that the same mechanism that limits the entry of viruses also deters their removal. Viral particles are cleared from the blood by the reticuloendothelial system; but if the viremia is massive or other conditions are favorable, they will invade the CNS probably via the cerebral capillaries and the choroid plexuses. Viruses cross into the nervous system both within migrating lymphocytes and directly through areas of glial and vascular regions that are permeable to ...

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