The Vasculopathy of Varicella-Zoster Virus Encephahtis Catherine Amlie-Lefond, MD,* Bette K. Kleinschmidt-DeMasters, MD,"? Ravi Mahalingam, PhD,* Larry E. Davis, MD,f and Donald H. Gilden, MD"5 ~ ~~ Varicella-zoster virus (VZV) encephalitis has become more prevalent in the era of acquired immunodeficiency syndrome and other immunosuppressive diseases and poses diagnostic and therapeutic challenges for clinicians, radiologists, and pathologists. Six cases studied at our institutions shed light on the patterns and pathogenesis of the disease. VZV encephalitis is predominantly a vasculopathy, involving small and large vessels, that generates seizures, mental changes, and focal deficits. Brain imaging reveals large and small ischemic or hemorrhagic infarcts, often both, of cortex and subcortical gray and white matter. Deep-seated white matter lesions often predominate and are ischemic andior demyelinative, depending on the size of blood vessels involved and the amount of additional demyelination caused by infection of oligodendrocytes. The demyelinative lesions are smaller and less coalescent than those seen in progressive multifocal leukoencephalopathy. Amlie-Lefond C, Kleinschmidt-DeMasters BK, Mahalingam R, Davis LE, Gilden DH. The vasculopathy of varicella-zoster virus encephalitis. Ann Neurol 1995;37:784-790 Diverse lesions develop after acute virus infection of the central nervous system (CNS) and depend in large part upon the cell type infected by virus. Necrosis follows infection of neurons by poliovirus, rabies, and togaviruses 11; fatal choriomeningitis develops after infection of choroid plexus, meninges, and ependyma by lymphocytic choriomeningitis virus [2}; demyelination occurs after lytic infection of oligodendrocytes by papovavirus 131; and a hemorrhagic encephalopathy is produced by parvovirus infection of endothelial cells [41. In varicella-zoster virus (VZV) encephalitis, the pathologic changes of vasculopathy leading to ischemiclhemorrhagic infarction and demyelination suggest that VZV is capable of infecting multiple cell types. To study the pathogenesis of disease, we combined clinical, radiologic, pathologic, and virologic studies of 6 patients with V Z V encephalitis. Case Histories Szcbject I A 54-year-old man with a 5-month history of Wegener's granulomatosis, Pneumocystis carinii infection, and renal insufficiency, taking cyclophosphamide (150 mgiday) and prednisone (80 mgiday), developed progressive leg weakness and numbness, difficulty urinating, and constipation over a month. He had experienced purpuric rash from HenochSchonlein disease. There was no history of zoster. Neurologic examination revealed spastic left leg weakness, a T12 From the Departments of 'Neurology, ?Pathology, and BMicrobiolom. Universitv of Colorado Health Sciences Center. Denver. CO: and $Neurology Service, Albuquerque VA Medical Center, and Deparrment of Neurology, University of New Mexico School Of Medicine, Albuquerque, NM.