A Poliomyelitis-like Syndrome from West Nile Virus Infection

Leis, A. Arturo; Stokić, Dobrivoje S.; Polk, Jo Lynn; Dostrow, Victor; Winkelmann, Michael

doi:10.1056/nejm2002c021587

Cited by 160 publications

(93 citation statements)

References 5 publications

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“…In the current study we extend previous observations that propose the presence of bystander neuronal death (Nargi-Aizenman et al, 2004), and we find that excitotoxic motor neuron injury is a critical determinant of NSV pathogenesis. It is interesting that related RNA viruses, most notably West Nile virus, have been shown to induce a flaccid paralysis characterized by spinal motor neuron death in animals (Kelley et al, 2003) and in a proportion of human cases (Leis et al, 2002). It is possible, therefore, that non-cell-autonomous excitotoxic death of motor neurons may be triggered by a variety of infectious agents and that strategies that target this process may be of therapeutic value.…”

Section: Introductionmentioning

confidence: 99%

Viral-Induced Spinal Motor Neuron Death Is Non-Cell-Autonomous and Involves Glutamate Excitotoxicity

Darman¹,

Backovic²,

Dike³

et al. 2004

J. Neurosci.

107

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Neuroadapted Sindbis virus (NSV) is a neurotropic virus capable of inducing the death of spinal motor neurons in mice and rats. In this study we investigated the mechanisms that underlie NSV-induced motor neuron death. We found that many degenerating spinal motor neurons were not infected directly with NSV, suggesting that bystander cell death occurs. An excitotoxic mechanism was confirmed when blockade of calcium-permeable AMPA receptors attenuated motor neuron death both in vitro and in vivo. Blockade of astroglial glutamate reuptake potentiated NSV-induced motor neuron loss in vivo, suggesting that astrocyte-mediated removal of perisynaptic glutamate is important in limiting NSV-induced excitotoxic injury. Astroglial glutamate transport was reduced markedly in the spinal cord during NSV infection, in advance of motor neuron injury in susceptible mice. In contrast, we found 5.6-fold elevated glutamate uptake in the spinal cords of mice resistant to NSV-induced paralysis. Likewise, minocycline markedly increased spinal cord glutamate transport and protected mice from NSV-induced motor neuron death. These studies suggest that NSV infection triggers a cascade of events in the spinal cord resulting in impaired astrocytic glutamate transport and excitotoxic injury of motor neurons mediated via calciumpermeable AMPA receptors. Similar changes may occur in other motor neuron disorders such as amyotrophic lateral sclerosis or West Nile Virus-induced poliomyelitis, suggesting a common tissue injury pathway.

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Section: Introductionmentioning

confidence: 99%

Viral-Induced Spinal Motor Neuron Death Is Non-Cell-Autonomous and Involves Glutamate Excitotoxicity

Darman¹,

Backovic²,

Dike³

et al. 2004

J. Neurosci.

107

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“…1-3 West Nile virus meningitis and encephalitis are often associated with favorable outcomes, 2 but when infection results in spinal anterior horn cell destruction it can cause an irreversible acute flaccid paralysis or poliomyelitis-like syndrome. [4][5][6][7][8][9][10][11] Movement disorders including parkinsonism, tremor and myoclonus have also been described. 2,[12][13][14] We present the clinical and neuropathologic findings in a ABSTRACT: Background: Patients infected with West Nile virus (WNV) may develop acute neurologic disease, which can be severe or even fatal, including WNV meningitis, encephalitis, and an irreversible acute flaccid paralysis or poliomyelitis-like syndrome.…”

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confidence: 99%

West Nile Virus Encephalomyelitis with Polio-like Paralysis & Nigral Degeneration

Schafernak

Bigio

2006

Can. j. neurol. sci.

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West Nile virus (WNV) is a mosquito-borne RNA virus in the genus Flavivirus (family Flaviviridae), and a member of the Japanese encephalitis serological group which comprises eight virus species including Japanese encephalitis virus (JEV) and St. Louis encephalitis virus (SLEV), and two subtype viruses. 1 Although most cases of WNV infection are subclinical or result in a mild, self-limited febrile illness known as West Nile fever, a minority of patients (<1%) develop acute neurologic disease, which can be severe and even fatal. 1-3 West Nile virus meningitis and encephalitis are often associated with favorable outcomes, 2 but when infection results in spinal anterior horn cell destruction it can cause an irreversible acute flaccid paralysis or poliomyelitis-like syndrome. [4][5][6][7][8][9][10][11] Movement disorders including parkinsonism, tremor and myoclonus have also been described. 2,[12][13][14] We present the clinical and neuropathologic findings in a ABSTRACT: Background: Patients infected with West Nile virus (WNV) may develop acute neurologic disease, which can be severe or even fatal, including WNV meningitis, encephalitis, and an irreversible acute flaccid paralysis or poliomyelitis-like syndrome. Movement disorders have also been described. Report: We report combined neuronal loss, gliosis, and neurofibrillary tangle formation in the substantia nigra of a 41-year-old man with a history of WNV encephalomyelitis and poliomyelitis-like paralysis. Conclusions: Clinically our patient did not display parkinsonism, however, it is interesting to speculate whether, in the absence of the residual subacute poliomyelitis-like syndrome, the neuropathologic findings could have eventually evolved clinically into WNV-associated postencephalitic parkinsonism. RÉSUMÉ: Encéphalomyélite due au virus du

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“…46 In addition to encephalitis, West Nile infection can result in myelitis, causing a poliolike illness. 47,48 Imaging abnormalities in the spine can include spinal cord or nerve T2 hyperintensity or enhancement. 46 Equine encephalitis viruses, of which there are 3 major types in the Western hemisphere, have been of special interest for biowarfare.…”

Section: Viruses: Encephalitis and Hemorrhagic Feversmentioning

confidence: 99%

Armies of Pestilence: CNS Infections as Potential Weapons of Mass Destruction

Hart

Ketai

2014

AJNR Am J Neuroradiol

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SUMMARY:Infectious agents have been investigated, developed, and used by both governments and terrorist groups as weapons of mass destruction. CNS infections, though traditionally considered less often than respiratory diseases in this scenario, may be very important. Viruses responsible for encephalitides can be highly infectious in aerosol form. CNS involvement in anthrax is ominous but should change treatment. Brucellosis, plague, Q fever, and other bacteria can uncommonly manifest with meningoencephalitis and other findings. Emerging diseases may also pose threats. We review infectious agents of particular concern for purposes of biowarfare with respect to CNS manifestations and imaging features. God omnipotent is mustering in his clouds on our behalf armies of pestilence.Richard II, Act 3, Scene 3 S hakespeare had Richard II threaten his enemies with "armies of pestilence" from the clouds-a prospect that seems more plausible in our time when incidents involving anthrax, smallpox, and hemorrhagic fevers continue to make headlines. Many infectious agents have been developed during the past century for potential military use. By their nature, these are unconventional weapons more effective against unprotected, civilian targets than against soldiers; this attribute may make them attractive to terrorists. Among those organisms, some target the central nervous system. For others more commonly considered pulmonary or systemic agents, significant CNS effects may still result. Below, we review the historical background, some of the organisms considered at high risk for potential biowarfare or bioterrorism with a focus on neurologic implications, and potential future threats.

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A Poliomyelitis-like Syndrome from West Nile Virus Infection

Cited by 160 publications

References 5 publications

Viral-Induced Spinal Motor Neuron Death Is Non-Cell-Autonomous and Involves Glutamate Excitotoxicity

Viral-Induced Spinal Motor Neuron Death Is Non-Cell-Autonomous and Involves Glutamate Excitotoxicity

West Nile Virus Encephalomyelitis with Polio-like Paralysis & Nigral Degeneration

Armies of Pestilence: CNS Infections as Potential Weapons of Mass Destruction

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