Update on the Cluster of Children with Unexplained Paralysis Identified During an Enterovirus D68 Outbreak in Colorado

At IDWeek 2014, one of the physicians from the admitting hospital reviewed the facts of the case, outlined the testing strategy utilized during the epidemiologic investigation into the causes of the paralysis, discussed possible factors suggesting an association with EV-D68, and provided an update on the prognosis of the affected children.

As previously reported on HCPLive, several children were admitted to Children’s Hospital Colorado in Denver, CO, in August and September with limb weakness and paralysis. When news hit that several of the children also tested positive for enterovirus D68 (EV-D68), clinicians and public health efforts began investigating a possible link between the virus and these new neurological symptoms. The Centers for Disease Control and Prevention (CDC) issued an official advisory though its Health Alert Network asking physicians and others to report any such cases to state and local authorities, or to the CDC.

With interest in these cases still running high, Kevin Messacar, MD, Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, delivered an update to a packed room Friday at IDWeek 2014 in Philadelphia, PA.

Messacar began his presentation, titled “Cluster of Acute Flaccid Paralysis and Cranial Nerve Dysfunction in Children Temporally Associated with an Enterovirus D-68 Outbreak in Colorado,” by reviewing the recent history of outbreaks of enterovirus D68. Noting that since 2008, EV-D68 “has been an increasingly recognized cause of respiratory disease outbreaks in Asia, Europe, and the US,” with large outbreaks of respiratory illness confirmed in August 2014 in Missouri and Illinois, followed soon thereafter by reports of cases across the country.

Messacar said that 19 of 25 respiratory rhinovirus/enterovirus specimens from patients admitted to the pediatric intensive care unit at his hospital were typed as EV-D68 by reverse transcription—polymerase chain reaction (RT-PCR).

Then, on August 19, the first child with acute neurologic illness characterized by extremity weakness was admitted to Children's Hospital Colorado (CHC). Over the next month, this index case was followed by six additional children admitted to the hospital with “acute flaccid paralysis (AFP) and/or cranial nerve dysfunction with distinctive imaging abnormalities,” said Messacar. After notifying state health authorities and the CDC, the staff at Children's Hospital Colorado began an epidemiologic investigation.

For the purposes of the investigation, the team tested all children admitted to CHC in August and September with acute flaccid paralysis and/or cranial nerve dysfunction and “spinal cord lesions predominantly affecting the gray matter and/or brainstem lesions on MRI.” The team collected cerebrospinal fluid, blood, nasopharyngeal specimens, throat cultures, and rectal swabs/stool samples.

A total of 10 children met the case definition during the outbreak period. Messacar said the youngest patient was 13 months old and the oldest was 18, with a median age of 9 years. There were 7 male patients and 3 females, with 9 of the kids living in the Denver metro area. Nine of 10 were up to date on immunizations, 2 had a history of asthma, 1 was a heart transplant recipient, and 2 had recently been prescribed steroid medications.

All patients had preceding febrile illness, and 9 had upper respiratory symptoms, occurring 3—16 days (median = 6.5 days) before onset of neurologic illness. Messacar said 8 patients exhibited “meningeal signs” (stiff neck, headache, photophobia).

Eight of 10 children presented with flaccid limb weakness that in most cases was asymmetric and hyporeflexic, with intact sensation. Nine children had cranial nerve dysfunction with 5 showing bulbar symptoms (hypophonia, dysarthria, and/or dysphagia). Several children experienced dysfunction at cranial nerve 6 and 7. No patient had seizure or encephalopathy.

Magnetic resonance imaging revealed 9 children had central gray matter lesions (most often in the cervical spinal cord) with predominant anterior horn involvement that were “confluent and longitudinally extensive,” said Messacar. Nine children had brainstem lesions.

Nine patients had cerebrospinal fluid pleocytosis with a median white blood cell count of 55 and “normal to mildly elevated” CSF. Nasopharyngeal specimens from 7 of 9 patients were positive for rhinovirus/enterovirus, including 4 cases of EV-D68 and one of rhinovirus (RV-A24).

In terms of treatment, Messacar said that the patienst had exhibited minimal to no clinical response to therapy, including IV immunoglobulin, IV methylprednisolone, plasmapharesis, and pocapavir. Four patients required “prolonged inpatient rehabilitation,” said Messacar, and all 9 have “residual deficits to date, with unknown long-term prognosis.”

Summarizing his talk, Messacar said there were several factors suggesting a connection between the neurological symptoms and EV-D68, including the timing of the cases, the fact that nearly every child had preceding febrile respiratory illness, and that half of nasopharyngeal specimens were positive for EV-D68. He also noted that “neurologic exam, neuroimaging, and EMG suggest a tropism for motor neurons similar to EV-A71 and poliovirus.”

He also noted several factors pointing away from an association with EV-D68, including the fact that, again, only half of nasopharyngeal specimens were positive, and that the “virus was not identified in CSF, serum, throat, rectal swab/stool,” said Messacar.

In his concluding remarks, Messacar said this was “the first geographic and temporal cluster of acute flaccid paralysis and cranial nerve dysfunction associated with an outbreak of EV-D68 respiratory disease,” and that the epidemiologic investigation is ongoing. He recommended early testing of suspected cases with nasopharyngeal specimens, in addition to the other tests conducted in this case. All cases should be reported to state health authorities and the CDC.