Electrodiagnostic findings in acute flaccid myelitis related to enterovirus D68

Hovden, Inger Anette Hynås; Pfeiffer, Helle Cecilie Viekilde

doi:10.1002/mus.24738

Cited by 26 publications

(27 citation statements)

References 7 publications

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“…6,7,20 Consistent with neuroimaging findings, electrophysiological changes were most commonly observed in the C5 to C7 levels in the upper extremity. Electromyographical changes were also observed in muscle groups and limbs that were clinically unaffected.…”

Section: Reviewsupporting

confidence: 74%

Acute flaccid myelitis: A clinical review of US cases 2012–2015

Messacar

Schreiner

Haren

et al. 2016

Annals of Neurology

199

301

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This review highlights clinical features of the increasing cases of acute flaccid paralysis associated with anterior myelitis noted in the United States from 2012 to 2015. Acute flaccid myelitis refers to acute flaccid limb weakness with spinal cord gray matter lesions on imaging or evidence of spinal cord motor neuron injury on electrodiagnostic testing. Although some individuals demonstrated improvement in motor weakness and functional deficits, most have residual weakness a year or more after onset. Epidemiological evidence and biological plausibility support an association between enterovirus D68 and the recent increase in acute flaccid myelitis cases in the United States.

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Section: Reviewsupporting

confidence: 74%

Acute flaccid myelitis: A clinical review of US cases 2012–2015

Messacar

Schreiner

Haren

et al. 2016

Annals of Neurology

199

301

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show abstract

“…EV-D68 appears to have strong in vivo tropism for motor neurons, as opposed to neurons in general. Human AFM patients present with inflammation and the loss of motor neurons in the brain stem and spinal cord but do not show signs of generalized encephalitis (7,10). Consistent with this observation, studies with mouse models developed by several independent research groups have shown that infection by contemporary EV-D68 strains results in minimal replication within the brains of infected animals but robust replication in spinal cord and muscle tissue (17,41,42).…”

Section: Discussionmentioning

confidence: 76%

“…Since 2014, recently evolved lineages of EV-D68, particularly those from subclade B1, have been implicated as a cause of acute flaccid myelitis (AFM), a polio-like paralytic condition that results due to viral infection and injury to the lower motor neurons of the spinal cord (6,7). Patients present with a viral prodrome typically consisting of fever and upper respiratory symptoms, followed days later by the development of progressive motor weakness with evidence for damage and loss of motor innervation on magnetic resonance imaging (MRI) and electromyography (EMG) (7)(8)(9)(10). EV-D68 is predominantly a respiratory pathogen, and the mechanism by which it travels from its initial site of replication in the upper respiratory tract to the spinal cord remains unclear.…”

mentioning

confidence: 99%

Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

Hixon

Clarke²,

Tyler

2019

J Virol

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Enterovirus D68 (EV-D68) is an emerging virus that has been identified as a cause of recent outbreaks of acute flaccid myelitis (AFM), a poliomyelitis-like spinal cord syndrome that can result in permanent paralysis and disability. In experimental mouse models, EV-D68 spreads to, infects, and kills spinal motor neurons following infection by various routes of inoculation. The topography of virus-induced motor neuron loss correlates with the pattern of paralysis. The mechanism(s) by which EV-D68 spreads to target motor neurons remains unclear. We sought to determine the capacity of EV-D68 to spread by the neuronal route and to determine the role of known EV-D68 receptors, sialic acid and intracellular adhesion molecule 5 (ICAM-5), in neuronal infection. To do this, we utilized a microfluidic chamber culture system in which human induced pluripotent stem cell (iPSC) motor neuron cell bodies and axons can be compartmentalized for independent experimental manipulation. We found that EV-D68 can infect motor neurons via their distal axons and spread by retrograde axonal transport to the neuronal cell bodies. Virus was not released from the axons via anterograde axonal transport after infection of the cell bodies. Prototypic strains of EV-D68 depended on sialic acid for axonal infection and transport, while contemporary circulating strains isolated during the 2014 EV-D68 outbreak did not. The pattern of infection did not correspond with the ICAM-5 distribution and expression in either human tissue, the mouse model, or the iPSC motor neurons. IMPORTANCE Enterovirus D68 (EV-D68) infections are on the rise worldwide. Since 2014, the United States has experienced biennial spikes in EV-D68-associated acute flaccid myelitis (AFM) that have left hundreds of children paralyzed. Much remains to be learned about the pathogenesis of EV-D68 in the central nervous system (CNS). Herein we investigated the mechanisms of EV-D68 CNS invasion through neuronal pathways. A better understanding of EV-D68 infection in experimental models may allow for better prevention and treatment strategies of EV-D68 CNS disease.

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“…EV-D68 infected cases associated with neurological symptoms were also reported in other countries such as in France, United Kingdom, Italy, Norway and Australia262728293031. However, the authors of these studies either only submitted partial sequences of VP1 (207–861bp), or did not provide the sequences.…”

Section: Discussionmentioning

confidence: 99%

Genetic divergence of enterovirus D68 in China and the United States

Zou

Xie

Liu

et al. 2016

Sci Rep

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The largest outbreak of human enterovirus 68 (EV-D68) infections associated with severe respiratory illness and neurological complications emerged from the United States in 2014. China reported the circulation of EV-D68 since 2006, but these cases were sporadic and did not display neurological symptoms. Yet viral determinants responsible for the difference in prevalence between China and the U.S. were not clear. We analyzed the genome of 64 reported Chinese EV-D68 strains and found that genogroup replacement has occurred in China since 2006. The six coding mutations (M291T, V341A, T860N, D927N, S1108G and R2005K) associated with neurovirulence reported in American strains were not found in Chinese strains. Moreover, 2014 Chinese strains had a unique R220A mutation in the puff region of VP2 while R220E mutation occurred in other strains. Like other enteroviruses, the loop sequences of the domain X and Y in the 3′-UTR of the Chinese strains are complementary. However, the X loop sequences of the 2014 American strains were not complementary but identical to Y loop sequences. These results indicate that different EV-D68 strains circulated in China and America and the mutations might be responsible for different prevalence. Our findings also provide new evidence for the sequence diversity of EV-D68.

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Electrodiagnostic findings in acute flaccid myelitis related to enterovirus D68

Cited by 26 publications

References 7 publications

Acute flaccid myelitis: A clinical review of US cases 2012–2015

Acute flaccid myelitis: A clinical review of US cases 2012–2015

Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

Genetic divergence of enterovirus D68 in China and the United States

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