To parents and the press, the “new” disease that is paralyzing kids is a mystery. Media coverage of acute flaccid myelitis (AFM), which causes sudden limb weakness and paralysis in children, has given families the impression that health care providers and public health officials are sitting quietly and helplessly, flummoxed in the face of a disease that threatens children’s health.
That just isn’t so.
Parents have a right to be concerned about this illness. But they should also know that AFM is rare, a one-in-a-million event. It does not spread within families, hospitals, or towns. Although a virus called enterovirus D68, along with other viruses that cause respiratory and diarrheal illness, has been linked to the disease, a single definitive cause hasn’t yet been identified. This isn’t because we aren’t looking: Physicians, scientists, and public health officials are working tirelessly to find answers and the best treatments.
Progress has been made on multiple fronts since 2014, when acute flaccid myelitis first emerged in news headlines and the public consciousness. In the clinical arena, multidisciplinary and multicenter collaborations have been tapping the collective wisdom of experts in infectious disease, neurology, neuroradiology, and rehabilitation, leading to the development of best practices for clinical care. Epidemiologic and research data on the disease are being shared across centers to optimize and standardize the approach to how children afflicted with this condition are cared for at any center across the country.
At Children’s National Health System in Washington, D.C., where we work, specialized programs have long been in place to combat emerging infections and neuroinflammatory disorders. Both of these are relevant to acute flaccid myelitis due to its association with viruses and the nerve inflammation it causes. Thanks to our program and similar programs in place at other pediatric medical centers, evidence-based, standardized clinical pathways now guide the evaluation and treatment of every child suspected to have acute flaccid myelitis.
As with other types of brain and spinal cord injury, the best results often come with early mobilization, so rehabilitation begins early, sometimes even while a child with AFM is in the intensive care unit. Pediatric physical therapists are trained to make children with weak limbs feel like they are champions, whether they are infants, toddlers, or older children.
On the epidemiologic and public health fronts, the Centers for Disease Control and Prevention has standardized and publicized case definitions so children with AFM can be identified. And the CDC recently announced a new task force on acute flaccid myelitis. Its work, which will be coordinated by the Office of the Director, aims to make its first report public in early December.
Multiple medical centers and surveillance networks have begun more intense and broad efforts to look at patterns of specific respiratory and diarrhea virus circulation in communities and have initiated targeted viral surveillance to detect spikes in frequency that might be associated with a subsequent spike in AFM cases.
On the scientific front, investigators have applied advanced molecular techniques, including whole exome genetic sequencing, to better understand enterovirus D68, as well as to exclude other agents that might contribute to AFM.
Investigators have also successfully developed laboratory and animal models of acute flaccid myelitis that closely mimic the human disease. These preclinical models provide a deeper understanding of how AFM injures the spinal cord and have helped identify possible treatment targets. Researchers are also screening off-the-shelf drugs and compounds that might work for these targets, and have already tested and reported on the safety and effectiveness of promising treatments.
Our health system has established a research biobank for blood and spinal fluid samples from children with neuroinflammatory diseases. Studying these specimens could lead to discoveries about AFM and new insights into how it affects individuals. Children’s National is one of the few pediatric hospitals that engineers antiviral treatments tailored to the individual patient that target the exact virus he or she has been infected with. That approach can be potentially lifesaving for the treatment of devastating viral infections that affect patients with defects in their immune system.
The first polio epidemic in the U.S. began in 1894; Franklin Delano Roosevelt got polio in 1921; Dr. Jonas Salk gave his vaccine to his family in 1953; and the vaccine developed by Dr. Albert Sabin was licensed in 1960. That’s a span of 66 years. Sabin’s highly effective and routinely used polio vaccine is often underappreciated for its essential role in safeguarding health and preventing a disease that paralyzed up to 20,000 children a year in the pre-vaccination era.
With modern techniques and multi-center collaborations, we hope that the time frame to solve acute flaccid myelitis will be much shorter than it was for polio. But it won’t occur overnight. Physicians and scientists need public and governmental support to speed progress. To effectively contend with AFM — and the next emerging infectious disease — the nation needs to enhance and intensify existing surveillance networks for viral diseases, expand laboratory investigation models to determine how disease occurs and how to treat it, and help major pediatric hospital networks share data, conduct clinical trials, and optimize care.
Even while all of that is happening, clinicians in our program and similar ones at other pediatric centers across the country apply continually updated information to guide a standardized approach to evaluate and treat children with acute flaccid myelitis and help them achieve the best possible chance of full recovery.
Roberta L. DeBiasi M.D., is chief of the Division of Pediatric Infectious Diseases, Elizabeth M. Wells, M.D., is medical director of the neurosciences unit, and Jessica Carpenter, M.D., is associate professor of pediatrics and neurology, all at Children’s National Health System in Washington, D.C.
Editor’s note: This article was updated to more accurately reflect the Children’s National/NIAID research partnership.
If not already being done, could be worth checking for specific presence of Coxsackie A10 and anti-aquaporin antibodies, based on references below from limb weakness case findings linked to this specific virus strain.
Note virus titer in first case dropped significantly within 4 weeks.
A case of poliomyelitis-like syndrome.
Brain Dev. 1998 Oct;20(7):540-2.
The authors report the case of a boy aged 4 years who had sudden abdominal pain and inability to walk on the day before admission to hospital and who developed abdominal distention and difficulty urinating. On admission, the abdominal skin reflexes, knee jerks, cremaster and anal reflexes were absent and power in the lower extremities was reduced….the titer of Coxsackie virus antibody type A10 was 128 in the acute phase and only 32 in the recovery phase 4 weeks later. ”
Neuromyelitis optica preceded by hyperCKemia and a possible association with coxsackie virus group A10 infection.
Intern Med. 2013;52(23):2665-8.
“The patient initially showed general fatigue with fever. Laboratory findings showed hyperCKemia and subsequently she developed a slight weakness of both lower limbs and reduced vision. Autoantibodies against aquaporin 4 were found in her serum, and a retrospective examination of viral titers indicated a possible coxsackie virus group A10 infection. “
I keep thinking about the possibility of a virus particle , still not traceable , that is able to join the Polio and Cocksakie B viruses. Seem to be with the sting of the beer or to a key that would cling to the mentioned viruses…..May be .
As for the previus text the translation was so bad that even I could not understand.
And this is a serious matter.
Perhaps the difficulty in finding the suspected virus is related to insufficient sampling of CD19+ B lymphocytes, which are known to harbor enteroviruses and poliovirus, as described below. Maybe these infected lymphocytes are present in CSF in amounts statistically too low to enable detection of the carried virus without cell sorter selection and/or a concentration procedure for the sample prep. In addition, continuing carriage of such a virus by immune cells for potential delivery to neuromuscular sites could also help to explain the very lengthy recovery period for AFM, not truly starting until all such infected B cell clones are eliminated.
“Moreover, CVB3 also infects immune cells like CD19+ B lymphocytes, but the viral uptake mechanism into these cells is not well understood.” Antibody-dependent enhancement of coxsackievirus B3 infection of primary CD19+ B lymphocytes.
Viral Immunol. 2010 Aug;23(4):369-76.
“However, recent studies show that Type B coxsackievirus (CVB) infects B lymphocytes soon after infection, suggesting the possibility that these cells may play some role in virus dissemination and/or that the virus may be able to modulate the host immune response.”
The role of B lymphocytes in coxsackievirus B3 infection.
Am J Pathol. 1999 Oct;155(4):1205-15.
“CVB3 replicated effectively in leukocytes of B-cell, T-cell, and monocyte origin, CVA24 in leukocytes of B-cell and monocyte origin…These findings suggest that the susceptibility of human leukocytes to non-polio EVs may be responsible for virus transport during the viremic phase, particularly to secondary target organs, and that active replication of CVB3 in all human leukocyte lineages leads to greater dissemination, in agreement with the ability of CVB to cause systemic diseases.”
Characterization of infections of human leukocytes by non-polio enteroviruses.
“Furthermore, in peritoneal lavage, poliovirus was also present in CD19(+) B cells, but not in dendritic or T cells.”
Pathogenesis of poliovirus infection in PVRTg mice
J Gen Virol. 2003 Oct;84(Pt 10):2819-28.
Perhaps the mechanism for AFM is actually a “2-hit” process as seen in the clear pattern in the thematically consistent abstracts below. It is based on injury to skeletal muscle that facilitates access for a strain of enterovirus (polio, EV68, EV71) to motor neurons.
Hence, the development of AFM could arise from First having exposure to a strain of enterovirus virus, followed by muscular injury caused by an intramuscular injection or instead perhaps an injury such as a physical fall or stick poke.
One interesting observation is that an induced enterovirus infection didn’t cause paralysis withOUT an accompanying muscle injury.
An interesting avenue to consider is whether children are receiving flu or any other IM vaccines shortly after contracting and then supposedly “clearing” an enterovirus infection, but with some remaining viable enterovirus actually still in circulation or tissue.
Mechanism of injury-provoked poliomyelitis.
J Virol. 1998 Jun;72(6):5056-60.
Gromeier M1, Wimmer E.
Skeletal muscle injury is known to predispose its sufferers to neurological complications of concurrent poliovirus infections. This phenomenon, labeled “provocation poliomyelitis,” continues to cause numerous cases of childhood paralysis due to the administration of unnecessary injections to children in areas where poliovirus is endemic. Recently, it has been reported that intramuscular injections may also increase the likelihood of vaccine-associated paralytic poliomyelitis in recipients of live attenuated poliovirus vaccines. We have studied this important risk factor for paralytic polio in an animal system for poliomyelitis and have determined the pathogenic mechanism linking intramuscular injections and provocation poliomyelitis. Skeletal muscle injury induces retrograde axonal transport of poliovirus and thereby facilitates viral invasion of the central nervous system and the progression of spinal cord damage. The pathogenic mechanism of provocation poliomyelitis may differ from that of polio acquired in the absence of predisposing factors.
PMID: 9573275 PMCID: PMC110068
A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice.
Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13636-41.
Dufresne AT1, Gromeier M.
Coxsackievirus A21 (CAV21) is classified within the species Human enterovirus C (HEV-C) of the Enterovirus genus of picornaviruses. HEV-C share striking homology with the polioviruses (PV), their closest kin among the enteroviruses. Despite a high level of sequence identity, CAV21 and PV cause distinct clinical disease typically attributed to their differential use of host receptors. PV cause poliomyelitis, whereas CAV21 shares a receptor and a propensity to cause upper respiratory tract infections with the major group rhinoviruses. As a model for CAV21 infection, we have developed transgenic mice that express human intercellular adhesion molecule 1, the cell-surface receptor for CAV21. Surprisingly, CAV21 administered to these mice via the intramuscular route causes a paralytic condition consistent with poliomyelitis. The virus appears to invade the CNS by retrograde axonal transport, as has been demonstrated to occur in analogous PV infections. We detected human intercellular adhesion molecule 1 expression on both transgenic mouse and human spinal cord anterior horn motor neurons, indicating that members of HEV-C may share PV’s potential to elicit poliomyelitis in humans.
PMID: 15353596 PMCID: PMC518806
Provocation of poliomyelitis by multiple injections.
Trans R Soc Trop Med Hyg. 1985;79(3):355-8.
Injections of vaccines provoked paralytic poliomyelitis in children in the UK and elsewhere. The effect of multiple injections has not been recognized previously but could be important in the tropics where children receive many injections. A number of epidemics of poliomyelitis between 1914 and 1962 are related to children with congenital syphilis or yaws under treatment with arsenicals or penicillin. Rates of 25% of children with paralysis occurred in epidemics while in non-epidemic periods the increase in susceptibility was about 25 fold. Other possible cases of provocation are discussed. Although in the tropics injections before paralysis may be causal, it will be difficult to prove that they are not coincident. The very high rate of paralysis following multiple injections is powerful evidence that injections in the tropics are often causal.
Poliomyelitis in developing countries: lower limb paralysis and injections.
Trans R Soc Trop Med Hyg. 1989 Jul-Aug;83(4):545-9.
The distribution of muscle paralysis due to poliomyelitis is different in temperate and tropical countries. In temperate countries, 49% of children with paralysis were affected only in the legs compared with 85% in developing countries, 79% and 89% respectively had affected legs with other paralysis. This suggests that correction for lameness surveys is unnecessary. Muscles frequently injected and those with adjacent motor neurone tracts in the central nervous system were much more frequently affected in Nigerian than in UK children, whereas paralysis in other muscles was less frequent than in the UK children. This and other evidence points to a major causal role for injections in the high prevalence of polio in developing countries. Proof may however be impossible to obtain because less than 0.5% of all injections are followed by paralysis. There may also be damage to motor neurones, without paralysis, which may lead to later disabilities. Injections should be given to young children only when absolutely necessary.
Unnecessary injections given to children under five years.
Indian J Pediatr. 1993 May-Jun;60(3):451-4.
Ashwath D1, Latha C, Soudarssanane MB, Wyatt HV.
Adults accompanying 64 children attending a hospital out-patient clinic were questioned about treatment and injections given for illnesses in the previous month. Half the children had received injections, almost all given by private doctors: we consider most of these injections to have been unnecessary. Three girls were paralysed by aggravation poliomyelitis after unnecessary injections. Adults approved of injections although they did not know what was injected.
Unnecessary injections and poliomyelitis. [Indian J Pediatr. 1993]
No. Most of our kids did not have any injuries around onset. Next to none had a recent vaccine.
Don’t just come up with random a&&a theories.
Escrevo em Portugues porque o assunto é complexo e minha leitura em inglês é bem melhor e mais complexa que minha escrita !!
Quando li , pela primeira vez sobre o assunto, me assustou a proporção de casos ( os primeiros relatados ) e pensei que seria possivel um vírus pólio-resistente ,ou a Pólio-like ser um HTLV mais diferenciado. Ainda acho possivel estas duas situações, ainda mais que tenho como quase certo, por mais que não hajam grandes evidencias exceto as que li em Revista de Neurologia da Dinamarca ou Suécia ( não estou bem certa qual destes paises ) sobre a suspeita de alteração da Vit. D e a presença do HTLV em casos de doenças musculares e de Escleros Múltipla. Foi um artigo que apenas tocava nestas possibilidades, mas lembrando que o clima destas regiões são bem diferentes e a incidencia do Sol também é baixa.
Pois bem, tentei buscar o numero de casos de Paralisia Flácida Aguda em regiões Norte – Americanas de pouco sol .Ou com um aumento de casos de depressão ( ligados à pouca exposição ao sol e baixa de Vit D ) e não achei uma constante : Os casos acontecem em diversas regiões, algumas com periodo solar bem grande e intenso , e sem as comorbidades da diminuição da Vitamina D ( Hipovitaminose D ).
Já os casos de HTLV foram procurados por voces e algumas crianças apresentam presença do vírus, mas outras não , o mesmo acontecendo com o vírus da diarreia infecciosa mais comum , o enterovírus D 68.
Isto sem falar da presença de Viroses respiratórias primárias ( ou não ) com ou sem a presença de D 68 mas acompanhadas da Paralisia Flácida Aguda.
Mas desde a primeira leitura também ocorreu-me que haveria possibilidade de uma partícula víral, ainda não detectada , ou detectável , associar-se a alguns destes vírus, aumentando a letalidade e causando um acesso ao SNC de forma ainda não bem entendida.
Não tenho laboratório para estudar esta possibilidade , e a idéia de partículas virais , que se aproximem de diversos vírus que não necessariamente sejam de uma mesma familia, levando – o a produzir determinado sintoma me tem fascinado há mais de quatro anos . Talvez apenas um fascinio de um novo campo …
Porém ,quando li sobre o Ébola que surgiu na África e onde se intensifica a campanha para a erradicação da Pólio novamente ocorreu -me a possibilidade desta chamada partícula viral ser mais real do que apenas uma fascinação com um novo termo ou com um novo campo submicrocópico a ser estudado.
É a Mielite Flácida Aguda de Causa Indeterminada , hoje , uma incógnita e um caminho longo a percorrer, concordo.
Quanto à conduta : A fisioterapia precoce -melhorando o resultado final -não demonstra que o esforço da musculatura, gerando componentes químicos constantes da contração e relaxamento musculares seriam capazes de desativa-lo, ou diminuir seu potencial lesional ?
Assim a possibilidade das substancias como sódio, potássio,cálcio , creatinina, prostaglandinas e outras interferir e fragilizar esta partícula, talvez tornando sua ligação mais lenta ou até desativa-la seria uma pesquisa mais rápida , o que é a necessidade dos pacientes tendo em vista que urge uma medicação ou atuação vacinal mais específica.
Agradeço se os pesquisadores me respondessem.Tenho tradutor neste link , pode ser em ingles.
It would be interesting to know if big data, like IBM’s Watson, could analyze patient records to look for commonalities in the cases we might not be seeing. Theoretically, this would be a faster way to identify the causative agent, which may or may not be viral.
To whom this may concern,
I am a parent of a child with AFM. She was hit with this devastating disease back in September of 2016. I would like to mention that we as the parents are not pointing fingers at physicians across this country, or our communities public officials, but rather devastated by the lack of urgency of creating awareness for this “life threatening disease” by the CDC. Meanwhile the CDC was a direct cause by empeeding you physicians by not offering updated protocols, by not getting proper literature to emergency rooms, and by not creating a sense of urgency when it comes to this life threatening disease. And trust me when I say life threatening, there have been 2 deaths this year and I literally watched my child die multiple times – within 15 hours her diaphragm paralyzed. (Unfortunately about 40% of children have Acute Respiratory Failure & that’s a fact) Once the virus mutates you only have hours to try and gain some sort of control because it replicates in frequency so in other words it’s fast moving and there wasn’t much we could have done, however, that all said it speaks to the TIMING of treatments. We should start by understanding this disease should be considered Nationally Notifiable.
After personally meeting with Principal Deputy Director Anne Schuchat and having her acknowledge all that I’ve mentioned above and she ultimately advised that Yes there has been a disconnect on every level and that they plan to change this effective immediately, by strengthening their processes moving forward. I’m proud to say today that things are moving in the right direction. And Now we the Parents move forward in meeting with Congress in February in the hopes AFM gets the funding it needs, so we can look forward to cohort studies, collecting proper data for updated treatments, money for education, such as public announcements and hopefully one day find a cure. I write to you in the hopes that you more clearly understand where we the parents are coming from.
Please know all your help in finding answers, your research, your wisdom is considered of great value to all of us.
Gina is right that the causative agent may not be viral, and that a broader look is needed for commonalities among the cases. But as a toxicologist, I think the problem is less what “we might not be seeing” than what AFM experts clearly see but nevertheless do not recognize.
All the symptoms of AFM reported by CDC, for example, are also reported in the medical literature on carbon monoxide poisoning, and CO also is well known to commonly have a flu-like onset. But CDC and others studying AFM don’t mention this possibility and don’t recommend CO testing, even though the levels of CO diffusing from arteries, veins and tissues can be easily measured non-invasively via exhaled breath, and many treatments are available.
CO poisoning may be the result of inhaled exogenous (external) exposures and/or higher than normal endogenous (internal) exposures. All humans make CO 24/7 via an enzyme called heme oxygenase and moreso in response to stressors of any kind, including spinal injuries and infections of all kinds. So people can get CO poisoning even without inhaling any CO.
The article shows too much focus on viruses. The cause could be environmental or idiopathic. When you don’t know the cause, you should not bet everything on one vector.
Science has clear evidence this disease is entrovirus. (99% sure)
Don’t make up random theories without actually having data to back you up, Barry. The CDC has data that shows a virus in most cases (often viral tests aren’t done in time) and a fever in 99% of cases. Fever from a virus.
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