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A number of viruses share a predilection to primarily affect the human nervous system. The clinical presentations of these infections vary greatly, and while there is considerable overlap in the manifestations, there are also important features that help designate which infection is most likely in a particular scenario, often guiding appropriate diagnostic evaluation and treatment decisions. The systemic effects of the viral infection can vary; in some cases, the systemic features may be negligible, and it is the neurologic disorder that brings them to medical attention. Included in this group are the group of human herpes viruses including 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 exhibit 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 glial cells; John Cunningham (JC) virus causing progressive multifocal leukoencephalopathy (PML) 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 may induce multiple foci of tissue necrosis throughout the cerebrum.

Pathways of Infection

Viruses gain entrance to the body by various routes. 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), ticks, mites, or mosquitoes (arthropod-borne or arbovirus infections). The fetus may be infected transplacentally by rubella virus, CMV, and HIV. In all these cases, viremia is an intermediate step to seeding the brain or cerebrospinal fluid (CSF).

Another pathway of infection is along peripheral nerves; centripetal movement of the virus is accomplished by the retrograde axoplasmic transport system. HSV, VZV, and rabies virus utilize this peripheral nerve pathway, which explains why the initial symptoms of rabies occur locally, at a segmental level corresponding to the animal bite. HSV may spread to the central nervous system (CNS) via olfactory neurons, whose central processes of these cells pass through openings in the cribriform plate and synapse in the olfactory bulb. Another potential pathway is the trigeminal nerve and gasserian ganglion following primary infection of the nasopharynx. VZV resides in the sensory ganglia and becomes reactivated later in life, causing shingles decades after the primary infection that produces chicken pox. The JC virus also is latent in tissues, possibly the kidney and bone marrow, only to reemerge under conditions of immunosuppression to infect the brain.

Mechanisms of Viral Infections


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