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
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.
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 ...