Varicella-zoster virus (VZV) encephalitis has become more prevalent in
the era of acquired immunodeficiency syndrome and other immunosuppres
sive diseases and poses diagnostic and therapeutic challenges for clin
icians, radiologists, and pathologists. Six cases studied at our insti
tutions shed light on the patterns and pathogenesis of the disease. VZ
V encephalitis is predominantly a vasculopathy, involving small and la
rge vessels, that generates seizures, mental changes, and focal defici
ts. Brain imaging reveals large and small ischemic or hemorrhagic infa
rcts, often both, of cortex and subcortical gray and white matter. Dee
p-seated white matter lesions often predominate and ate ischemic and/o
r demyelinative, depending on the size of blood vessels involved and t
he amount of additional demyelination caused by infection of oligodend
rocytes. The demyelinative lesions are smaller and less coalescent tha
n those seen in progressive multifocal leukoencephalopathy.