ABSTRACT
The role of brain biopsy in CNS viral diagnosis has diminished with widening availability of validated molecular and serologic assays to detect a variety of pathogens in cerebrospinal fluid and blood. In current practice guidelines, biopsy has no role in initial diagnostic procedures, and is generally considered only when suspected agents cannot be confirmed or when acceptable timeframes for diagnosis have lapsed. However, as new forms of CNS viral infection are recognized, biopsy has another role in delineating pathogenesis of emerging or atypical infections. Viral neuropathology is influenced by the route of CNS invasion, cellular viral tropism, relative permissiveness of CNS cell types to support the viral life cycle, and host immune response. CNS inflammation is a typical, albeit not universal, manifestation of infection, including lymphoid-predominant leptomeningitis, encephalitis, ventriculitis, and vasculitis, and monocyte and microglial responses ranging from compact and loose nodules to regions of prominent neuronophagia. Viral cytopathic effects such as inclusions and cytomegaly may or may not be diagnostic, and ancillary techniques such as immunohistochemistry and in situ hybridization for viral nucleic acids may be helpful in the neuropathologic workup.
