Earlier this month, the CDC issued a warning for parents, caregivers, and pediatric professionals to be on the lookout for children developing weakness and paralysis. As I’ll explain shortly, we are due for a surge in cases of a relatively new polio-like illness over the next few months. Adding to these concerns, we don’t know how the novel coronavirus pandemic will impact the incidence or the timeliness of diagnosis of these cases.
Acute flaccid myelitis, a new version of a classic disease
In 2012, although there were perhaps a few cases as early as 2009, the first clusters of what would come to be known as acute flaccid myelitis (AFM) emerged in the United States and Europe. These cases primarily involved early school-aged children developing sudden weakness, and in many cases the loss of the use of one or more of their extremities following a mild viral infection. Many of these children even lost the ability to breathe on their own. If this sounds familiar, it’s because that is the exact description of the clinical presentation of infection with the poliovirus.
As with poliomyelitis, more commonly known simply as polio, patients suffering from AFM present with dysfunction or death of anterior horn cells within the gray matter of the spinal cord which can be seen on MRI of the spine. These lower motor neurons innervate skeletal muscle, which become weak or flaccid as the disease progresses, often resulting in paralysis of the involved limbs. Historically, this clinical presentation has been labeled acute flaccid paralysis (AFP), which prior to the development of a safe and effective vaccine was almost universally caused by the poliovirus. AFM is the term now used to specifically designate these modern cases and to differentiate them from polio and from other rare infectious and non-infectious causes.
Most patients eventually diagnosed with AFM have a prodromal viral upper respiratory infection, vomiting, and/or diarrhea in the week or so prior to the onset of weakness. Once a child begins to have difficulty moving one or more of their extremities, progression of neurologic symptoms tends to occur relatively quickly. Hours to days, not weeks or months. Many have additional neurological concerns, such as incontinence or the loss of cranial nerve function. Virtually all patients require hospitalization and a third end up needing to be placed on a ventilator as the weakness progresses to involve respiratory muscles or the muscles of the mouth and throat. Not all patients survive.
A pattern emerges and the culprit is discovered
Cases of AFM continued to be reported after 2012, and a pattern of late summer and early fall predominance was established. A Colorado outbreak in 2014 led to the development of a national surveillance program run by the CDC and significant spikes were again seen in 2016 and 2018. The numbers have remained relatively low, but there has been a consistent increase in yearly totals with each biennial bump. There were 120, 153, and 236 proven cases in 2014, 2016, and 2018 respectively, with many more suspected but unproven cases. In the intervening years, case totals have dropped dramatically, with each having less than 50 proven cases.
Since those early reports, we have learned that the cause of almost all cases of AFM is enterovirus D68 (EV-D68), although there are other infectious agents to blame for some. One thing that has been conclusively proven is that none of these cases have been caused by the poliovirus, which does also happen to be an enterovirus. Enteroviruses are incredibly common and varied. In addition to the poliovirus (an enterovirus C species), another well-known example comes from the enterovirus A species, although it is better known as a coxsackievirus and the cause of hand, foot, and mouth disease.
There are non-polio enteroviruses known to cause a similar presentation as AFM. There are even non-enterovirus viral pathogens, such as the flavivirus that causes West Nile fever and at least one adenovirus, that can cause paralysis in children. There are also autoimmune conditions that are very rare. Only the poliovirus, EV-D68, and EV-A71 have been associated with endemic and epidemic cases of paralysis, however. EV-D68 was first isolated in California in 1962 and was a rare cause of illness until the last decade. Unlike the poliovirus, it behaves more like a respiratory virus with fewer of the gastrointestinal symptoms that are commonly experienced with polio.
It hasn’t been easy to prove a causal link between AFM and EV-D68. As with the poliovirus, it is difficult to culture or even find DNA fragments in spinal fluid, even using modern PCR technology. With polio, stool samples provided the most reliable source for diagnosis, but this isn’t true with EV-D68 infections. Researchers have had to rely on more creative and indirect means, such as the measurement of anti-enteroviral antibody synthesis in spinal fluid. EV-D68 has also frequently been found in respiratory samples from AFM patients, which again is indirect evidence but there has been no other candidate pathogen identified in these samples with any consistency. The biennial spikes also coincide with surges in EV-D68 circulation.
The search for an effective treatment continues
Sadly, there is no proven effective treatment for AFM. Supportive care, such as providing respiratory assistance when needed, and interventions aimed at limiting damage to the spinal cord are key aspects of acute management. Rehabilitation, starting as early as possible, is very important for improving long-term outcomes. Numerous immune-modulating pharmaceutical interventions have been tried, such as steroids and immune globulin, as well as various antiviral medications, but nothing has been shown to be helpful thus far. There really is no clear guidance for physicians caring for these patients.
Unfortunately, most children with AFM still have residual neurologic limitations despite aggressive rehabilitation when followed up a year or so after diagnosis. Not that there isn’t room for hope. The data is limited and this condition is still fairly new. It does appear that slow progress occurs, so we don’t really know how these patients will be doing in the more distant future.
Conclusion: Acute flaccid myelitis in the setting of the coronavirus pandemic
The bottom line is that we don’t know how the ongoing pandemic will change the course of this year’s predicted spike in AFM cases. It is possible, perhaps even likely, that we will see many fewer cases than expected if continued social distancing and the use of masks reduce the risk of spreading EV-D68. We have certainly seen fewer cases of just about every other communicable pediatric infectious disease over the past few months. Easily 75% of my non-newborn admissions since March have been mental health related, but that’s a topic for another day perhaps.
We might also see a delay in the timely diagnosis of AFM when it does occur. This might happen because of hesitance out of concerns for exposure to the novel coronavirus and fear of developing COVID-19. I’m not really worried that any children with blatant paralysis won’t be brought in for evaluation, although I suppose that it is possible. The problem is that a caregiver might not seek care when a child has the milder weakness typically seen earlier in the course. This might make a difference in that child’s prognosis. We just don’t have enough data yet to really know what, if anything, might improve outcomes, and we don’t know if earlier treatment prior to the development of frank paralysis makes a difference either.
So, spread the word and be on the lookout for young kids with weak arms or legs. There have been 16 cases so far in 2020, which is on track with previous years prior to the biennial fall surges. As summer draws to a close, we are going to know how this is going to go pretty soon.