The herpes family (herpes simplex I and II, cytomegalovirus, varicella zoster, Epstein-Barr) deserves special emphasis because of both the high rates of morbidity and mortality associated with these infections and the availability of effective pharmacotherapy for some. All herpes group viruses contain double-stranded DNA, and drugs of proven efficacy specifically target the viral encoded thymidine kinase enzyme that catalyzes viral DNA replication.
Herpes simplex encephalitis is the most common form of lethal non-epidemic encephalitis in the West, with an annual incidence between 1 and 2 per 500 000 persons. Without therapy, mortality exceeds 70 per cent and only about 10 per cent of survivors will regain normal neurological function. In children aged less than 6 months, adolescents, and adults, herpes simplex encephalitis is a focal brain infection, typically localized to one or both temporal lobes or somewhat less frequently the orbitofrontal and mesiofrontal (limbic) regions. In contrast with the neonatal form, which is commonly caused by herpes simplex type II, 'adult' herpes simplex encephalitis is almost always caused by herpes simplex type I and may be associated with primary infections or reactivations. In adults, herpes simplex virus type II central nervous system infections are generally seen in immunodepressed individuals and present as a viral meningitis or, less commonly, as an encephalomyelitis.
The pathogenesis of herpes simplex encephalitis remains illusive. It is generally agreed that the route of viral entry into the central nervous system is via neural structures, in particular the trigeminal ganglia and the olfactory bulbs after viral penetration of the nasal mucosa. However, encephalitis generally occurs on reactivation of the virus at a later time (approximately two-thirds of cases). Once established, the progression of herpes simplex encephalitis is usually rapid and necrotizing. Cerebrospinal fluid is frequently hemorrhagic and the pleocytosis is mild to moderate with a predominance of mononuclear forms. Recent experimental work with herpes simplex encephalitis has emphasized the capacity of herpes simplex I to suppress facets of T-cell activation essential for effective immune surveillance without interfering with the generalized inflammatory response to tissue necrosis. As the infection spreads, the parenchymal inflammation and associated brain swelling are generally severe. Brain swelling reflects a combination of cytotoxic and vasogenic edema and cerebral hyperemia (vascular engorgement).
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