Is it possible for enterovirus to be the next acute flaccid myelitis?

Bacteria

Enterovirus D68 has historically been a rare sporadic disease-causing occasional small outbreaks and a generally mild infection. Mostly these were respiratory in nature like a runny nose, cough and muscle aches. Recently the illness and caused more severe disease and has been focusing more in children. The first large-scale outbreak of EVD68 was reported in the US and Canada. From August 2014 to January 2015 a total of 1153 cases in 49 states with 10.4% cases of acute flaccid myelitis in the US and five cases of EVD68 in Canada. Several clusters of acute flaccid myelitis have been noted in recent years associated with EVD68 and EVA71. further investigation into the relationship is important because of the severity of acute flaccid myelitis and because there currently is no treatment for acute flaccid myelitis related to EVD68 or vaccines to prevent it (Dyda et al, 2018).

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Does acute flaccid myelitis encompass subgroups with distinct clinical presentations and possible alternative diagnosis?
Looking at 45 patients who met the CDC definitions of acute flaccid myelitis, 24% had a definable alternative neurological diagnosis. Clinical characteristics were found that distinguished between a homogenous group of patients with acute flaccid myelitis and a subgroup of children with a definable alternative diagnosis that fulfills the broader acute flaccid myelitis definition.

Acute flaccid myelitis is an emerging polio-like illness affecting children with a clinical spectrum and associated pathogens that are only partially known. It is felt that acute flaccid myelitis most likely involves multiple neurologic diagnoses. It is thought there could even be an overlapping of symptoms thus further research is very important to discover the actual cause. The study found alternate diagnosis like transverse myelitis, spinal cord stroke, Guillain-Barré syndrome, Chiari myelopath and meningitis to name a few that further complicates the search for an actual cause of acute flaccid myelitis and prompting a great need for better diagnosis, treatment, and prevention of further cases (Elrick et al, 2018).

What is this disease?
Acute Flaccid Myelitis has been defined as an acute onset of weakness in any limb in a person of any age and either MRI indicating spinal lesions largely restricted to the grey matter and spanning more than one vertebral segment or cerebral spinal fluid with a white blood cell count of more than five cells/mm³. enterovirus D68 and A71 have both been detected in 10 confirmed cases of acute flaccid myelinitis. The median patient age was six years with seven male and three female. Median interval from onset of respiratory symptoms t the onset of neurological was two days. For nine patients fever was reported in the four weeks before the onset of limb weakness. All patients initially had acute onset of weakness in one or more limbs among this cluster of ten patients but no common etiology or source of exposure was identified. Clinicians’ specifically pediatric neurologists should maintain vigilance for acute flaccid myelitis. They are encouraged to report cases as soon as possible to state and local health departments to add to information regarding clinical signs, severity and illness prognosis (Bonwitt et al, 2017).

And yet this is not poliomyelitis
As of the writing of this study, poliomyelitis has been almost eradicated worldwide. In spite of this cases of a polio-like disease with asymmetrical flaccid paralysis of variable severity have been repeatedly seen in recent years. Against this background since 2012 an increasing number of severe cases with flaccid paralysis have been observed in various countries. The scary thing for most parents is that in some cases the disorder presents to health care workers very similar to poliomyelitis did when it was common.

And unlike Guillain-Barré Syndrome, there was no evidence of demyelization so typical of this condition. Acute flaccid myelitis only appears to affect sensory or motor function. Spinal MRI found 84% involvement of cervical cord with 80% thoracic and 47% medullary involvement noted. Polio-like causes of acute encephalitis with flaccid paralysis in children have been noted in many European countries and the US in recent years. It has been indicated that some of these illnesses have been caused by enterovirus D68 but while it has been found in stool or respiratory samples-there has been very little direct causation found; more studies and clinical reporting needs to be done (Hübner et al, 2017).

Just how common is this disorder?
Until 2013 enterovirus D68 was considered rare and only caused sporadic cases and minor outbreaks of respiratory infections. Since 2014 EV-D68 has gained epidemiological and clear relevance due to a large-scale outbreak of severe respiratory infections mostly in children, in the US and Canada. After that there were other countries affected as well. In the US there was a decrease in respiratory disease from EV-D68 but instead of an increase in severe neurological disease-mainly acute flaccid myelitis. And while D68 was not noted in the spinal fluid there is still a possibility of it causing a polio-like disease was still considered. Other enterovirus, EV-A71 in particular, is known to be neurotropic or localized selectively in nerve tissue and can cause aseptic meningitis, meningoencephalitis and acute flaccid myelitis. And while the children do recover from this it has had evidence of residual weakness after up to one month of treatment. Outbreaks of D68 have not shown more than respiratory elements however recent outbreaks have shown to be due to D68 leading to the suggestion it has now become neurotropic in nature much like A71 (Esposito et al, 2017).

Just this past summer
In May 2018 Colorado Department of Public Health and Environment was notified of an increase in cases of meningitis and encephalitis in children that tested positive for enterovirus. In a five year period 2013-2017 thera e was documented 2.75-fold increase in encephalitis of unknown cause and three-fold rise in enterovirus/rhinovirus detection during the same period. In August 2018 enterovirus A71 was detected in 34 children with a neurologic disease. Of those patients with A71 central nervous system infections onset of symptoms occurred two to five months prior to admission. Of these 12 had meningitis, nine encephalitis, and three had acute flaccid myelitis. Severe A71 infection can cause brainstem encephalitis leading to cardiopulmonary collapse and polio-like acute flaccid myelitis. It is important that health care providers need to consider A71 as a causative agent when patients present with fever also show involuntary muscle jerks, lack of muscle control or coordination of voluntary movements. This can include trouble with speech, eye movement, swallowing difficulties as well as routine acute flaccid myelitis surveillance (Messacar et al, 2018).

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Conclusion
Enteroviruses are thought to have existed with humanity for thousands of years. One of the oldest records of enterovirus is an Egyptian carving thought to illustrate a priest with a withered limb. The causative agent of poliomyelitis was not discovered until 1908. It was one of the first enterovirus discovered. After President Franklin Roosevelt became paralyzed by poliomyelitis the National Foundation for Infantile Paralysis was formed to find a vaccine for it. In 1955 Dr. Jonas Salk developed the first inactivated injectable vaccine. Then in 1961 Dr. Albert Sabin developed the first oral form of the vaccine.

In the majority of patients, D68 only causes mild respiratory illness. Recently D68 has started to show an increase in severity of both respiratory disease but also in causing a polio-like paralysis known as acute flaccid myelitis. It had also started to focus primarily on children. Further outbreaks of D68 should be expected with acute flaccid myelitis cases increasing. And just like poliomyelitis before it, there is a great need for further testing to be done in an effort to develop a vaccine to limit the chances of more children to be stricken with acute flaccid myelitis (Cassidy et al, 2018).

Works cited
Bonwitt, J. et al. (2017). Acute flaccid myelitis among children-Washington, September to November 2016. MMWR, 66(31).

Cassidy, H. et al. (2018). Enterovirus D68-the new polio? Frontiers in Microbiology

Dyde, A. et al. (2018). The association between acute flaccid myelitis and enterovirus D68-what is evidence for causation. Eurosurveillance, 23(3).

Elrick, M. J. et al. (2018). Clinical subpopulations in a sample of North American children diagnosed with acute flaccid myelitis, 2012-2016. JAMA Pediatrics.

Esposito, S. et al. (2017). Acute flaccid myelitis associated with enterovirus-D68 infection in an otherwise healthy child. BMC Virology Journal, 14(4).

Hübner, J. et al. 2017). Acute flaccind myelitis in German children in 2016-the return of Polio? Deutches Ärzteblatt International.

Messacar, K. et al. (2018). Enterovirus A71 neurologic disease in children-Colorado 2018. MMWR, 67(36).

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