Varicella-Zoster virus infections of the nervous system: clinical and pathologic correlates.
BACKGROUND
Diseases that present with protean manifestations are the diseases most likely to pose diagnostic challenges for both clinicians and pathologists. Among the most diverse disorders caused by a single known toxic, metabolic, neoplastic, or infectious agent are the central and peripheral nervous system complications of varicella-zoster virus (VZV).


METHODS
The pathologic correlates of the neurologic complications of VZV infection, as well as current methods for detecting viral infections, are discussed and presented in pictorial format for the practicing pathologist.


RESULTS
Varicella-zoster virus causes chickenpox (varicella), usually in childhood; most children manifest only mild neurologic sequelae. After chickenpox resolves, the virus becomes latent in neurons of cranial and spinal ganglia of nearly all individuals. In elderly and immunocompromised individuals, the virus may reactivate to produce shingles (zoster). After zoster resolves, many elderly patients experience postherpetic neuralgia. Uncommonly, VZV can spread to large cerebral arteries to cause a spectrum of large-vessel vascular damage, ranging from vasculopathy to vasculitis, with stroke. In immunocompromised individuals, especially those with cancer or acquired immunodeficiency syndrome, deeper tissue penetration of the virus may occur (as compared with immunocompetent individuals), with resultant myelitis, small-vessel vasculopathy, ventriculitis, and meningoencephalitis. Detection of the virus in neurons, oligodendrocytes, meningeal cells, ependymal cells, or the blood vessel wall often requires a combination of morphologic, immunohistochemical, in situ hybridization, and polymerase chain reaction (PCR) methods. The PCR analysis of cerebrospinal fluid remains the mainstay for diagnosing the neurologic complications of VZV during life.


CONCLUSIONS
Varicella-zoster virus infects a wide variety of cell types in the central and peripheral nervous system, explaining the diversity of clinical disorders associated with the virus.
Kleinschmidt-DeMasters
B K
BK
Department of Pathology, The University of Colorado Health Sciences Center, Denver, CO 80262, USA. BK.DeMasters@UCHSC.edu
Gilden
D H
DH
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000134:cerebrospinal fluid; D002490:Central Nervous System / Q000473:pathology / Q000821:virology; D002644:Chickenpox / Q000175:diagnosis* / Q000473:pathology; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006562:Herpes Zoster / Q000175:diagnosis* / Q000473:pathology; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007121:Immunocompetence; D016867:Immunocompromised Host; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000473:pathology; D009437:Neuralgia / Q000175:diagnosis / Q000473:pathology; D010525:Peripheral Nerves / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction
D000914:Antibodies, Viral