Since its introduction to the United States in 1999, West Nile virus (WNV) has become endemic in North America and has emerged as the most common cause of epidemic meningoencephalitis in North America and the leading cause of arboviral encephalitis in the United States. West Nile virus is maintained in nature by cycling between mosquito vectors and bird hosts; humans are incidental hosts. Transmission to humans occurs predominantly after a bite from an infected mosquito but has also occurred via transfusion of blood products, via organ transplantation from infected donors, transplacentally, and percutaneously through occupational exposure. Approximately one of 150 patients develops central nervous system manifestations, including meningitis, encephalitis, and acute flaccid paralysis/poliomyelitis. Risk factors for neuroinvasive disease include older age and immunosuppression. Imaging findings are nonspecific, and cerebrospinal fluid findings include pleocytosis, elevated protein, and normal to decreased glucose. The diagnosis is made in most patients on serological examination. Reverse transcription polymerase chain reaction tests are useful to screen blood products and for surveillance of birds and mosquitoes. The pathological findings are typical of a viral meningoencephalitis and include microglial nodules, perivascular chronic inflammation, and variable neuronal loss with necrosis or neuronophagia. Treatment is largely supportive, and control of the mosquito vectors may reduce the incidence of human infections.

Rare cases of West Nile virus (WNV)-associated inflammation outside the central nervous system (CNS) have been reported. We evaluated the systemic distribution of WNV in postmortem tissues during encephalitis in six patients using immunohistochemistry. WNV antigens were detected in neurons of CNS (all 6 cases), kidney (4 cases), lungs (2 cases), pancreas (2 cases), thyroid (2 cases), intestine (2 cases), stomach (1 case), esophagus (1 case), bile duct (1 case), skin (1 case), prostate (1 case) and testis (1 case). In systemic organs epithelial cells were infected. In none of the six cases were viral antigens identified in hepatocytes, heart, adrenal gland, nerves, skeletal muscles, bone, vessels and fat. All cases in which viral antigens were identified in systemic organs in addition to CNS were severely immunocompromised transplant recipients. With the exception of testis and brain, most foci of infection were not associated with inflammation. While the absence of inflammation may in part be due to patient immunosuppression or to possible transient nature of any host response, compartmentalization of viral antigen to the luminal region of epithelial cells may sequester WNV from immune recognition. Comparison of our findings with previous reports suggests that patients with WNV encephalitis can have widespread systemic infection.

Childhood ataxia with diffuse central nervous system hypomyelination syndrome (CACH) is a recently described leukodystrophy of unknown etiology. To characterize the neuropathological features and gain insight as to the pathogenesis of this disorder, we studied cerebral tissue from six patients with the CACH syndrome. Evaluation of toluidine blue-stained, semithin sections of white matter from CACH patients disclosed unusual cells with "foamy" cytoplasm, small round nuclei and fine chromatin. Electron microscopy (EM) revealed cells in the white matter with abundant cytoplasm containing many mitochondria and loosely clustered, membranous structures, but lacking the lysosomal structures seen in macrophages. Further analysis of tissue sections with antibodies and special stains demonstrated that the abnormal cells with abundant cytoplasm labeled with oligodendroglial markers, but did not react with macrophage or astrocytic markers. Double immunolabeling with macrophage and oligodendroglial markers clearly distinguished macrophages from the "foamy" oligodendroglial cells (FODCs). Proteolipid protein (PLP) mRNA in situ hybridization demonstrated PLP mRNA transcripts in a high proportion of oligodendrocytes in CACH patients compared to control patients, and PLP mRNA transcript signal in cells, morphologically consistent with FODCs. Normal and pathological brain control tissues did not contain FODCs. These neuropathological findings will be useful pathological identifiers of CACH, and may provide clues to the pathogenesis of this disorder.

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We report the case of a 47-year-old man who developed progressive multifocal leukoencephalopathy (PML) after receiving immuno-suppressive therapy for renal transplantation. The patient presented with a focal seizure and cognitive changes 5 months posttransplantation. He was found to have enhancing lesions in the parietal lobe and typical findings of PML in a brain biopsy. Immunosuppression was discontinued and the neurological symptoms gradually resolved over a period of 4 weeks. The patient is free of any neurological symptoms 36 months after the diagnosis of PML and imaging studies demonstrate resolution of the PML lesions. The patient returned to hemodialysis 3 months after immunosuppression was discontinued. We also present a review of the literature on PML in renal transplant recipients.