Histopathologically Proven Poliomyelitis with Quadriplegia and Loss of Brainstem Function Due to West Nile Virus Infection

Doron, Shira; Dashe, John F.; Adelman, Lester S.; Brown, William F.; Werner, Barbara G.; Hadley, Susan

doi:10.1086/377177

Cited by 68 publications

(57 citation statements)

References 18 publications

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“…It has been assumed that respiratory failure in neuroinvasive disease due to WNV infection is caused by respiratory muscle weakness including both diaphragm and intercostal muscles, similar to that in poliomyelitis [30,31]. Pathological inspection of the spinal cord of patients who had died from respiratory failure in WNV infection revealed gliosis, neuronal loss and inflammation in the anterior horns of the cervical spinal cord and brainstem [32].…”

Section: Discussionmentioning

confidence: 99%

Outbreak of West Nile virus infection among humans in Serbia, August to October 2012

Popović¹,

Milošević

Urošević³

et al. 2013

Eurosurveillance

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We describe the first reported outbreak of West Nile virus (WNV) infection in humans in Serbia in August to October 2012 and examine the association of various variables with encephalitis and fatal outcome. Enzyme-linked immunosorbent assay (ELISA) was used for detection of WNV-specific IgM and IgG antibodies in sera and cerebrospinal fluid. A total of 58 patients (mean age: 61 years; standard deviation: 15) were analysed: 44 were from Belgrade and its suburbs; 52 had neuroinvasive disease, of whom 8 had meningitis, while 44 had encephalitis. Acute flaccid paralysis developed in 13 of the patients with encephalitis. Age over 60 years and immunosuppression (including diabetes) were independently associated with the development of encephalitis in a multivariate analysis: odds ratio (OR): 44.8 (95% confidence interval (CI): 4.93-408.59); p=0.001 (age over 60 years); OR: 10.76 (95% CI: 1.06-109.65); p=0.045 (immunosuppression including diabetes). Respiratory failure requiring mechanical ventilation developed in 13 patients with encephalitis. A total of 35 patients had completely recovered by the time they were discharged; nine patients died. The presence of acute flaccid paralysis, consciousness impairment, respiratory failure and immunosuppression (without diabetes) were found to be associated with death in hospital in a univariate analysis (p<0.001, p=0.007, p<0.001 and p=0.010, respectively).

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Section: Discussionmentioning

confidence: 99%

Outbreak of West Nile virus infection among humans in Serbia, August to October 2012

Popović¹,

Milošević

Urošević³

et al. 2013

Eurosurveillance

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“…␣-Motor neurons, large motor neurons in the anterior horn of the spinal cord (ventral horn in horizontal animals), are one of the primary targets in ALS (5), poliovirus (21), and for WNV (24). More specifically, WNV has been described as causing poliomyelitis-like disease, since it infects motor neurons in the anterior horn of the spinal cord (10,24). Since MUNE provides a sensitive marker for the progression of ALS (5) and polio (3), we anticipated correctly that it would also be a sensitive marker for West Nile neuroinvasive disease in the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation

Siddharthan

Wang

Motter

et al. 2009

J Virol

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To investigate the hypothesis that neurological sequelae are associated with persistent West Nile virus (WNV) and neuropathology, we developed an electrophysiological motor unit number estimation (MUNE) assay to measure the health of motor neurons temporally in hamsters. The MUNE assay was successful in identifying chronic neuropathology in the spinal cords of infected hamsters. MUNE was suppressed at days 9 to 92 in hamsters injected subcutaneously with WNV, thereby establishing that a long-term neurological sequela does occur in the hamster model. MUNE suppression at day 10 correlated with the loss of neuronal function as indicated by reduced choline acetyltransferase staining (R 2 ‫؍‬ 0.91). Between days 10 and 26, some ␣-motor neurons had died, but further neuronal death was not detected beyond day 26. MUNE correlated with disease phenotype, because the lowest MUNE values were detected in paralyzed limbs. Persistent WNV RNA and foci of WNV envelope-positive cells were identified in the central nervous systems of all hamsters tested from 28 to 86 days. WNV-positive staining colocalized with the neuropathology, which suggested that persistent WNV or its products contributed to neuropathogenesis. These results established that persistent WNV product or its proteins cause dysfunction, that WNV is associated with chronic neuropathological lesions, and that this neurological sequela is effectively detected by MUNE. Inasmuch as WNV-infected humans can also experience a poliomyelitis-like disease where motor neurons are damaged, MUNE may also be a sensitive clinical or therapeutic marker for those patients.

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“…West Nile virus (WNV), a flavivirus that cycles between mosquitoes and birds with humans and other mammals as incidental hosts, can cause severe, potentially fatal neurologic disease, including encephalitis, meningitis, paralysis, and anterior myelitis (12). Although neurons are the primary target of WNV infection, a hallmark of WNV encephalitis is the accumulation of inflammatory infiltrates extending from the meninges into the brain parenchyma that vary in severity between brain regions and consist predominantly of lymphocytes and macrophages (19).…”

mentioning

confidence: 99%

Neuronal CXCL10 Directs CD8⁺T-Cell Recruitment and Control of West Nile Virus Encephalitis

Klein

Lin

Zhang

et al. 2005

J Virol

388

455

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The activation and entry of antigen-specific CD8؉ T cells into the central nervous system is an essential step towards clearance of West Nile virus (WNV) from infected neurons. The molecular signals responsible for the directed migration of virus-specific T cells and their cellular sources are presently unknown. Here we demonstrate that in response to WNV infection, neurons secrete the chemokine CXCL10, which recruits effector T cells via the chemokine receptor CXCR3. Neutralization or a genetic deficiency of CXCL10 leads to a decrease in CXCR3؉ CD8 ؉ T-cell trafficking, an increase in viral burden in the brain, and enhanced morbidity and mortality. These data support a new paradigm in chemokine neurobiology, as neurons are not generally considered to generate antiviral immune responses, and CXCL10 may represent a novel neuroprotective agent in response to WNV infection in the central nervous system.

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Histopathologically Proven Poliomyelitis with Quadriplegia and Loss of Brainstem Function Due to West Nile Virus Infection

Cited by 68 publications

References 18 publications

Outbreak of West Nile virus infection among humans in Serbia, August to October 2012

Outbreak of West Nile virus infection among humans in Serbia, August to October 2012

Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation

Neuronal CXCL10 Directs CD8⁺T-Cell Recruitment and Control of West Nile Virus Encephalitis

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Histopathologically Proven Poliomyelitis with Quadriplegia and Loss of Brainstem Function Due to West Nile Virus Infection

Cited by 68 publications

References 18 publications

Outbreak of West Nile virus infection among humans in Serbia, August to October 2012

Outbreak of West Nile virus infection among humans in Serbia, August to October 2012

Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation

Neuronal CXCL10 Directs CD8+T-Cell Recruitment and Control of West Nile Virus Encephalitis

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Product

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Neuronal CXCL10 Directs CD8⁺T-Cell Recruitment and Control of West Nile Virus Encephalitis