by Dan Hurley
First seen in California, then in Colorado, cases of acute flaccid myelitis marked by strikingly consistent MRI evidence of gray matter damage in the spinal cord are now believed to be affecting children in multiple states across the United States, according to neurologists tracking the outbreak. The reports have provoked grave concern among some specialists that the syndrome could affect even more patients next year.
To date, there are numerous unknowns surrounding this quickly evolving outbreak. Neurologists are not sure what causes it, but an emerging theory holds that it is likely linked to the summer’s nationwide outbreak of upper respiratory infections caused by enterovirus 68, even though the virus has not yet been isolated from any cerebrospinal fluid or central nervous system tissue studied in the past year.
No one is sure how long the symptoms will last, but some neurologists say that, so far, short-term recovery has been minimal to moderate. They said they know of no significantly beneficial therapy, but some believe that treatment with steroids may be unhelpful and perhaps even detrimental. Perhaps most tellingly, they do not yet agree on what to call the condition, or how to define it.
Some neurologists even question whether the cases seen so far represent a significant increase over background rates of prior years, given the paucity of earlier surveillance data.
The polio vaccine. Image via Wikimedia Commons.
The size of the current outbreak in the United States led the Centers for Disease Control and Prevention (CDC) to issue a request on Sept. 26 to all physicians to look for and report cases of what is being called acute flaccid myelitis, or “polio-like syndrome,” to their state health departments. By Oct. 15, the agency had already verified 37 cases in 16 states.
The CDC case definition used in its Sept. 26 announcement requires that a patient meet four criteria: the patient must be no older than 21 years of age and show an acute onset of focal limb weakness, with an MRI showing a spinal cord lesion largely restricted to gray matter. Cases must also have occurred on or after Aug. 1, 2014.
“Anecdotally, it does seem as if there are an unusually large number of these cases,” James J. Sejvar, MD, a neuroepidemiologist leading the CDC’s response to the outbreak, told Neurology Today. “We know there is a large outbreak of enterovirus 68 in children. We’ve also seen this cluster of polio-like syndrome in Colorado, and we’re hearing of additional reports of polio-like syndrome in other parts of the country. It’s premature to say at this point that the polio-like cases are caused by enterovirus 68, but certainly that’s one of our leading hypotheses.”
The only report definitively linking an infection with enterovirus 68 with a neurologic disorder came from New Hampshire in 2011, in which a case of fatal meningomyeloencephalitis occurred in a 5-year-old boy.
Although the CDC has not yet issued any recommendations or guidelines on treating the condition, Dr. Sejvar said, “We will indeed eventually come out with guidelines.”
IS THIS A NEW SYNDROME?
The California neurologists who used the term “polio-like syndrome” in a series of five cases reported at the 2014 AAN Annual Meeting published a report in the Morbidity and Mortality Weekly Report (MMWR) on Oct. 10, in which they called the condition “acute flaccid paralysis with anterior myelitis.” The paper identified 35 cases seen in California between June of 2012 and June of 2014. By the publication date, however, the terminology had already changed again.
“We’ve stopped using ‘anterior’ because not all the cases we’ve been seeing are anterior,” said Keith Van Haren, MD, a pediatric neurologist at Stanford University School of Medicine. “The term we are now using is acute flaccid myelitis.”
Just one week after the MMWR publication, he added, “We’ve seen several more cases that look just like it.” Nationally, he estimated, “If we’re talking about 50 states, I think the number of cases in the past few months is going to be in the neighborhood of 100 or more.”
While the numbers are far from clear at this point, most of the neurologists interviewed by Neurology Today said the cases are so remarkably distinct and unusual that they represent a sharp increase from whatever the background rate was previously.
IS IT A POLIO-LIKE SYNDROME?
“What we’re looking at is a disease indistinguishable in most respects from traditional polio, in terms of its symptoms,” Dr. Van Haren said. “Until now it was a really rare bird. Before 2012, we saw maybe one case every five years that wasn’t attributable to West Nile. Since 2012, we’ve seen many more cases. And since just this summer, we’ve seen even more.”
Jayne M. Ness, MD, PhD, an associate professor in the division of pediatric neurology at the University of Alabama at Birmingham, said that three cases have been seen at Children’s of Alabama since August, as well as one case earlier in the year.
“The three cases since August really look like each other. They have severe arm flaccidity and no mental status changes. All of them have similar spine MRIs showing gray matter involvement. You could lay all three MRIs on top of each other and they look almost the same. It’s pretty striking.”
In three of the four cases, the flaccidity was limited to one arm, reminding Dr. Ness of a peripheral nerve injury.
“They cannot move the arm at all,” she said. “It you lift the arm up, it literally drops. Sensation is usually intact. There might be slightly decreased sensation in the other arm, but these are younger kids, so they’re not always so cooperative in giving you a good sensory exam.”
In Kansas City, Jean-Baptiste Le Pichon, MD, PhD, a child neurologist at Children’s Mercy Hospital, said that three cases had been seen since August, plus a possible fourth case that was seen recently.
Dr. Le Pichon said that when cases of severe upper respiratory infections associated with enterovirus 68 were identified earlier this past summer in Kansas City, “I was thinking that we would see some type of neurologic pathology. I queried the Child Neurology Listserv for anyone having seen neurological complications associated with EV68, and sure enough, two weeks later we had our first case.
“It takes a day or two to make a diagnosis,” he said. “We have to eliminate transverse myelitis or Guillain-Barré. We need a good history and the MRI.”
The presentation, he said, is “virtually identical” to polio.
“The sudden onset of flaccid paralysis in single or multiple limbs with absolutely no sensory findings, the MRIs all showing uniformly a signal increase in the ventral horns of the spinal cord — this is exactly the same region of the spinal cord affected in polio,” Dr. Le Pichon said.
“Almost all of the patients have an increase in their white-blood cells in the cerebrospinal fluid. Some of the patients have brainstem findings and cranial-nerve findings. This is all the same as what polio does. None of us has ever seen anything like this before, with few exceptions.”
The largest cluster of cases is in Colorado. Teri L. Schreiner, MD, MPH, a pediatric neurologist at Children’s Hospital Colorado in Denver, said that she knows of 29 cases so far, including 12 since August.
“I would have a high degree of suspicion in any patient who has had a prior respiratory illness or cranial nerve dysfunction, who presents with flaccid weakness of one or more limbs,” said Dr. Schreiner. “In any patient who presents with those criteria, I would strongly encourage the provider to get an MRI of the brain as well as the spinal cord. We have also been performing nerve conduction studies, and are seeing evidence of acute denervation as soon as one or two weeks from onset of weakness.”
“We ran a report using similar ICD9 codes for the prior five years,” Dr. Schreiner said. “What we are seeing this year is many times greater. We are seeing a distinct outbreak with very stereotyped MRI findings and a clinical presentation that is atypical from anything else we have ever seen.”
Despite the comparisons to classic polio, the current outbreak of acute flaccid myelitis does in fact have unique differences, said Avindra Nath, MD, chief of the Section of Infections of the Nervous System and clinical director of the National Institute of Neurological Disorders and Stroke.
“The poliovirus is transmitted through water or food. It has an oro-fecal transmission, and sometimes causes gastrointestinal symptoms. But enterovirus D68, which is the presumptive agent here, is spread through the air and can be isolated from the nasal passages. It’s going to affect muscles supplied by the cervical spinal cord and the brainstem.”
Look for the full article and discussion in the Nov. 16 issue of Neurology Today. For more coverage of the outbreak, browse our archives at http://bit.ly/1pwNJh1.
To report a case of acute flaccid myelitis to your state health department, or to see updated information from the CDC, go to http://bit.ly/entero-cdc. Some neurologists are sharing their observations on a child neurology listserv at http://bit.ly/listserv-cn.
Neurologists may also invite families to participate in an online registry and data repository organized by University of Texas Southwestern Medical Center. To find out more, families can send an email to firstname.lastname@example.org.