ARTICLE IN BRIEF
California researchers describe five cases involving children in California who appear to have a polio-like syndrome.
In 1979, after a successful national vaccination campaign, the US finally declared an end to the periodic polio epidemics that had caused severe illness in thousands of people each year. But recent reports of a mysterious “polio-like” illness in California serve as an important reminder of why polio should remain on the list of differential diagnoses for acute flaccid paralysis.
As many as 25 cases of this illness have been reported in California over the past 18 months; most of them in children. It is unclear whether additional cases have been seen in other states. Emmanuelle Waubant, MD, PhD, FAAN, professor of clinical neurology and pediatrics at the University of California-San Francisco School of Medicine, told Neurology Today that she first saw a patient with polio-like presentation in 2012, but could not identify the virus involved. The patient had been vaccinated against polio, and the “usual suspects” — West Nile virus, Herpes Simplex virus, Lyme disease, and others — were ruled out. When Dr. Waubant discussed the perplexing case with her pediatric neurology colleague, Keith Van Haren, MD, at Stanford, she discovered that he had just seen a child with similar symptoms. That child had also experienced upper respiratory symptoms just before the onset of the flaccid paralysis.
So began the search for a cause. “A third case showed up, so we started to think we needed to increase the awareness of the community because the cases were being misdiagnosed as transverse myelitis,” she told Neurology Today.
Led by Drs. Waubant and Van Haren, California investigators compiled data for an abstract for the AAN Annual Meeting in order to increase the visibility of these cases, ensure earlier diagnosis, and possibly identify additional cases seen by other physicians. The abstract is based on case reports of five California children, two of whom tested positive for enterovirus-68, a relatively uncommon virus that has been associated with respiratory infections in the past. A single case of encephalomyelitis was reported a few years ago with enterovirus-68. The exact etiology of the California cases of polio-like symptoms, however, remains unknown.
“Most of US practicing neurologists have never seen an acute case of polio because polio has been eradicated for many, many years in the Western world, and other infections associated with polio-like presentations are very rare. We have seen patients with chronic symptoms related to polio, but we never saw these patients in the acute phase.”
The investigators hope that increasing awareness will allow them to identify whether there has been an outbreak of cases, or if this is “business as usual.” Polio-like cases in the US are not a reportable condition, thus making it difficult to confirm an increase in incidence, she said.
What do these polio-like symptoms look like and how do they differ from transverse myelitis (TM)? Both TM and the polio-like illness have a rapid onset, said Dr. Waubant, with the maximum motor weakness occurring within 48 hours, and often less. However, there are some distinct differences, she added. Unlike TM, most of the time there are no other neurological symptoms such as sensory changes in patients with polio-like illness.
“With most cases of TM, you'll see an increase in the deep tendon reflexes. With our cases, because it's affecting the anterior horn, those reflexes are decreased or absent. Additionally, the motor deficit in our cases is predominantly proximal. So, it's a total paralysis of proximal muscles and the distal muscles are not as severely involved,” she added. “Also, unlike in TM cases, our cases remain flaccid over time; for example, they do not develop any spasticity or other pyramidal findings.”
Spinal MRI scans of the patients revealed non-enhancing T2 bright changes in the spinal cord, mostly of the central gray matter, she said. In the children who had an EMG, anterior horn involvement was confirmed. The patients also had mild pleocytosis, or increased cell count, with lymphocyte predominance in the cerebral spinal fluid. It is possible that some of the other cases reported may have had a normal cord MRI but instead had thickened roots on MR neurogram, Dr. Waubant explained.
The physical recovery of the five patients with polio-like illness was very poor — “from zero to marginal at best,” Dr. Waubant noted, despite aggressive initial treatment with pulse steroids, IVIG, and plasma exchange.
It is still unclear whether enterovirus-68 — found on nasopharyngeal swabs of two children — is related to the polio-like presentation, she said. “Unfortunately, a number of our cases were brought to our attention after several weeks and thus samples for viral studies may not have been contributive, especially in those receiving IVIG and plasma exchange,” she explained. “Also, enterovirus-68 is extremely difficult to identify in infected patients even in the acute phase.”
The investigators are working with the California Department of Public Health to learn more about the cases. “We are also working with the medical community to increase the awareness about these cases so they can be diagnosed earlier and appropriate samples (nasopharyngeal and mouth swabs, spinal fluid, serum, stool) can be sent promptly to Dr. Carol Glaser [chief of encephalitis and the special investigations section in the California Department of Public Health] for identification of the causal agent.” The goal is to understand whether a single virus is at fault in these cases, or whether there are several agents.
Importantly, said Dr. Waubant, there is no evidence of an epidemic because there has not been a rapid increase in the number of cases in the past 18 months.
The public is largely unfamiliar with the different clinical illnesses that cause acute flaccid paralysis, said Mark A. Pallansch, PhD, director of the Division of Viral Diseases at the Centers for Disease Control and Prevention (CDC) in Atlanta “so I think that the term ‘polio-like’ provides a reference point. But it may also have intensified the media's reaction to these reports in California.”
Acute flaccid paralysis (AFP) is a rare condition that occurs globally at a background rate of roughly one case per 100,000 children under the age of 15 with an etiology that is not well characterized in most situations, Dr. Pallansch said. If poliomyelitis (or the isolation of poliovirus from any clinical condition) is suspected, then that is reportable to the CDC. There are many countries that also report on non-polio AFP in support of the global polio eradication efforts, but the US and other developed countries largely do not.
Because cases of AFP are not recorded routinely, it is very probable that similar cases — at similar incidence rates — have been present in California (and other states) in the past, but we just do not have a definitive record, Dr. Pallansch explained.
One major challenge with central nervous system disease is the ability to collect appropriate specimens at appropriate times, he said. In order to fully test for polio in a patient who is suspected to have the disease, clinicians should look for anterior horn disease and residual paralysis after 60 days. It is also necessary to obtain two stool samples from the patient within two days of each other — ideally within the first two weeks of illness, Dr. Pallansch told Neurology Today.
The virus that was found in two of the California children, enterovirus-68, is not a new entity. “We've known about it for many decades. In the last 10 years, it appears to have had an increased incidence. It is almost exclusively associated with respiratory disease, including some severe lower respiratory disease in children, but there is no etiologic association with paralytic disease and enterovirus-68,” Dr. Pallansch said.
Based on the current evidence, the CDC cannot make any recommendations for preventative measures. For neurologists who see a case of flaccid paralysis with clear anterior horn cell involvement, he said, “polio should at least be considered in the differential.” But, Dr. Pallansch does not see a reason for alarm at this point.
Moving forward, said Dr. Pallansch, “there should be more etiologic studies into the different types of AFP. Some of them, like Guillain-Barré, are considered to be post-infectious but there are other types of AFP for which etiology is not established routinely and so there is an opportunity to do studies, but it's not going to be simple given the rare occurrence of these conditions.
“We're still working with the state of California to try to understand these cases better, so that is a work in progress.” The CDC has also received and is investigating additional case reports from other states at this time.
CALIFORNIA'S SURVEILLANCE OF ACUTE FLACCID PARALYSIS
The California Department of Public Health (CDPH) is currently conducting enhanced viral testing and surveillance for patients with acute flaccid paralysis. They are seeking information and specimens on patients meeting the following case definition:
Acute flaccid paralysis, including absent or significantly diminished reflexes in one or more limbs AND
* MRI showing grey matter involvement of the spinal cord OR
* EMG showing anterior horn cell disease
* With or without accompanying mental status changes
* Without a confirmed traumatic, neoplastic, arboviral, or vascular etiology
To optimize laboratory testing, the CDPH is requesting the following sample types, collected as close to onset date as possible:
* CSF (2–3cc, if available)
* Acute phase serum, collected prior to treatment with IVIG (2–3cc in red or tiger top tube)
* Nasopharynx swab (in viral transport media)
* Throat swab (in viral transport media)
* Two stool samples collected > 24 hours apart (quarter-sized amount in sterile wide-mouth container). Rectal swab in virus transport media acceptable if stool is unavailable
If you are aware of a case meeting the above definition, or you are interested in submitting patient samples, please contact Heather Sheriff (firstname.lastname@example.org; 510-307-8608) or Patrick Ayscue (email@example.com; 510-620-5847).
Source: California Department of Public Health: http://bit.ly/1iUBkmd
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