Sequelae of Western Equine Encephalitis

Mulder, Donuld W.; Parrott, Muriel; Thaler, Margaret

doi:10.1212/wnl.1.7-8.318

Cited by 52 publications

(23 citation statements)

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“…Western equine encephalitis and other encephalitides can also produce a chronic parkinsonian state, occasionally with delayed progression. 14,22 Most of the non-von Economo's cases did not have the oculogyric crises, dystonia, personality changes, or L-dopa responsiveness that occurred in most post-von-Economo's patients but not in ours.…”

Section: Postencephalitic Parkinsonism?mentioning

confidence: 68%

Woman with a 26‐year history of parkinsonism, supranuclear ophthalmoplegia, and loss of postural reflexes

et al. 2004

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Section: Postencephalitic Parkinsonism?mentioning

confidence: 68%

Woman with a 26‐year history of parkinsonism, supranuclear ophthalmoplegia, and loss of postural reflexes

et al. 2004

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“…Several reports suggested that WEEV infections of humans were associated with Parkinsonism following encephalitis recovery (4,30). Residual neurological effects can occur long after the WEEV infection has subsided and include tremor, intellectual deterioration, and cogwheel rigidity.…”

Section: Discussionmentioning

confidence: 99%

“…Outbreaks have led to significant rates of morbidity and mortality. Survivors can suffer from debilitating and sometimes progressive neurological sequelae (4). Aspects of alphavirus-induced CNS disease remain to be fully characterized, including the specific sites of virus entry into the CNS.…”

mentioning

confidence: 99%

Entry Sites of Venezuelan and Western Equine Encephalitis Viruses in the Mouse Central Nervous System following Peripheral Infection

Phillips

Rico

Stauft

et al. 2016

J Virol

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Venezuelan and western equine encephalitis viruses (VEEV and WEEV; Alphavirus; Togaviridae) are mosquito-borne pathogens causing central nervous system (CNS) disease in humans and equids. Adult CD-1 mice also develop CNS disease after infection with VEEV and WEEV. Adult CD-1 mice infected by the intranasal (i.n.) route, showed that VEEV and WEEV enter the brain through olfactory sensory neurons (OSNs). In this study, we injected the mouse footpad with recombinant WEEV (McMillan) or VEEV (subtype IC strain 3908) expressing firefly luciferase (fLUC) to simulate mosquito infection and examined alphavirus entry in the CNS. Luciferase expression served as a marker of infection detected as bioluminescence (BLM) by in vivo and ex vivo imaging. BLM imaging detected WEEV and VEEV at 12 h postinoculation (hpi) at the injection site (footpad) and as early as 72 hpi in the brain. BLM from WEEV.McM-fLUC and VEEV.3908-fLUC injections was initially detected in the brain's circumventricular organs (CVOs). No BLM activity was detected in the olfactory neuroepithelium or OSNs. Mice were also injected in the footpad with WEEV.McM expressing DsRed (Discosoma sp.) and imaged by confocal fluorescence microscopy. DsRed imaging supported our BLM findings by detecting WEEV in the CVOs prior to spreading along the neuronal axis to other brain regions. Taken together, these findings support our hypothesis that peripherally injected alphaviruses enter the CNS by hematogenous seeding of the CVOs followed by centripetal spread along the neuronal axis. IMPORTANCEVEEV and WEEV are mosquito-borne viruses causing sporadic epidemics in the Americas. Both viruses are associated with CNS disease in horses, humans, and mouse infection models. In this study, we injected VEEV or WEEV, engineered to express bioluminescent or fluorescent reporters (fLUC and DsRed, respectively), into the footpads of outbred CD-1 mice to simulate transmission by a mosquito. Reporter expression serves as detectable bioluminescent and fluorescent markers of VEEV and WEEV replication and infection. Bioluminescence imaging, histological examination, and confocal fluorescence microscopy were used to identify early entry sites of these alphaviruses in the CNS. We observed that specific areas of the brain (circumventricular organs [CVOs]) consistently showed the earliest signs of infection with VEEV and WEEV. Histological examination supported VEEV and WEEV entering the brain of mice at specific sites where the blood-brain barrier is naturally absent. E astern, Venezuelan, and western equine encephalitis viruses (EEEV, VEEV, and WEEV; Alphavirus; Togaviridae) are mosquito-borne viruses in the Americas causing central nervous system (CNS) disease in humans and equids (1). EEEV, VEEV, and WEEV are maintained in nature via transmission cycles between vertebrate hosts and specific mosquito species (2). Historically, these alphaviruses have caused sporadic epizootics and epidemics in horses and humans, respectively (1, 3). Outbreaks have led to significant rates of morbidity...

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“…The incidence of Parkinsonism in other forms of encephalitis is far less common, although it has been documented after western equine (Mulder et al, 1951). Coxsackie B (Walters, 1960), Japanese B (Richter and Shimojyo, 1961), measles (Meyer, 1943), and possibly polio virus encephalitis (Duvoisin and Yahr, 1965).…”

Section: Discussionmentioning

confidence: 99%

Oligoclonal banding in the cerebrospinal fluid of patients with postencephalitic Parkinsonism.

Williams¹,

Houff²,

Lees³

et al. 1979

Journal of Neurology, Neurosurgery & Psychiatry

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Sequelae of Western Equine Encephalitis

Cited by 52 publications

References 0 publications

Woman with a 26‐year history of parkinsonism, supranuclear ophthalmoplegia, and loss of postural reflexes

Woman with a 26‐year history of parkinsonism, supranuclear ophthalmoplegia, and loss of postural reflexes

Entry Sites of Venezuelan and Western Equine Encephalitis Viruses in the Mouse Central Nervous System following Peripheral Infection

Oligoclonal banding in the cerebrospinal fluid of patients with postencephalitic Parkinsonism.

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