Fatal Fulminant Pan‐Meningo‐Polioencephalitis Due to West Nile Virus

Abstract

We report a case of fatal fulminant West Nile virus (WNV) meningoencephalitis in an 87‐year‐old white male gardener. The Pennsylvania patient presented with a 3‐day history of flu‐like symptoms. His hospital course was gravely precipitous with onset of coma, ventilator dependence, loss of cortical and brainstem functions within ten days of admission. Acute serum and cerebrospinal fluid samples revealed elevated levels of WNV IgM antibodies by ELISA as well as elevated CSF white blood cells, protein and glucose. A complete autopsy revealed a multifocal lymphocytic myocarditis and severe chronic tubulointerstitial nephritis. Viral culture and PCR analysis of post‐mortem samples of the spleen, kidney and brain were positive for WNV. Histological sections from all regions of the brain and spinal cord demonstrated a severe, non‐necrotizing, subacute, polio‐meningoencephalitis. While both gray and white matter were inflamed, gray matter was much more severely involved. Many gray matter nuclei showed severe neuronal loss with residual dying neurons surrounded by activated microglia. Immunohistochemical stains revealed profuse infiltration of the meninges and cerebral parenchyma by CD8 T‐lymphocytes and perivascular B‐lympho‐cytes. Electron micrographs revealed diffuse intracellular and extracellular edema but no viral particles were identified. Immunohistochemical and immunofluorescent staining for WNV filled the cytoplasm of residual neurons. West Nile virus mediates a predominantly polioencephalitis secondary to direct infection of neurons.

Flavivirus Encephalitis

“…103 The pathological changes that occur in peripheral tissues infected with WNV remain incompletely characterized. In human cases, WNV has been detected in renal and splenic tissues, with cell culture and reverse transcriptase polymerase chain reaction; 85 in renal tubular epithelium of an AIDS patient, with IHC; 39 in testis of a transplant recipient, with electron microscopy; 110 and in macrophages, intravascular mononuclear cells, and vascular endothelia of the skin, stomach, lung, liver, kidney, spleen, and bone marrow, with IHC. 86 Systemic distribution of WNV in severely immunocompromised transplant recipients has been reported in whom the epithelial cells of the lung, pancreas, thyroid, intestine, stomach, esophagus, bile duct, skin, prostate, and testes were positive for viral antigen, based on IHC.…”

“…105 Mice that succumb to infection develop CNS pathology similar to that observed in human WNV cases. 29,85 Mouse lesions described in the literature include necrosis of neurons, perivascular mononuclear infiltrates mainly composed of macrophages and lymphocytes, glial/microglial nodules, neuronal satellitosis, and neuronophagia in the brainstem, cerebral cortex, hippocampus, cerebellum, and spinal cord. 13,31,106 Many studies recently performed on the pathogenesis of North American WNV isolates used the C57BL/6 mouse strain and genetically engineered immunocompromised mice in the C57BL/6 background.…”

Chemokines and Viral Infections of the CNS

“…The virus continues to replicate in the spleen, kidney, and epithelial tissues before it enters the CNS (Chung et al, 2007). After entering the CNS, through both retrograde axonal transport and hematogenous dissemination Hunsperger & Roehrig, 2006), WNV typically infects the brain stem, hippocampal, and spinal cord neurons (Eldadah & Nathanson, 1967;Omalu et al, 2003;Shrestha et al, 2003;Fratkin et al, 2004). Following infection of the CNS, CD4 + and CD8 + T cells, as well as NK cells and infiltrating monocytes/macrophages accumulate in the CNS and localize primarily in the vicinity of WNV-infected neurons.…”

Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

“…It is a condition that has been reported in WNV infected human [108,109,207], birds [110][111][112][113]238], dogs [239,240] and horses [49]. Associated cardiac arrhythmia, as described in some human case reports [108], may contribute to the overall morbidity of mice.…”

“…In fact, CD3+ T cells infiltration into the CNS was a common observation in human, NHP, and equine WNV infections [49,207,307]. Furthermore, upregulated IFNγ gene transcription in nucleated cells isolated from CSF samples of WNV-infected horses has been reported [23].…”