Neurologic Deficits in Children Preceded by Febrile Illness

Association Raises Specter of Possible Enterovirus D-68 Involvement

October 13, 2014 12:15 pm Chris Crawford

On Sept. 12, the Colorado Department of Public Health and Environment (CDPHE) notified the CDC that a cluster of nine children being evaluated at Children's Hospital Colorado were exhibiting acute neurologic illness characterized by extremity weakness, cranial nerve dysfunction (e.g., diplopia, facial droop, dysphagia or dysarthria), or both, according to an early release Morbidity and Mortality Weekly Report (MMWR)( posted on Oct. 3. These neurologic illnesses occurred from Aug. 8 to Sept. 15 in children ages 1-18 years.

[Young girl laying in hospital bed with oxygen]

Children from a dozen states have exhibited signs of acute neurologic illness. A number of the children have tested positive for enterovirus D-68, leading CDC officials to consider the possibility of a link between the two ailments.

Although the precise etiology of the illness remains unidentified, in each case, patients had experienced febrile illness, often associated with upper respiratory symptoms, within three to 16 days before the onset of neurologic symptoms.

On Sept. 19, the CDPHE issued a health alert informing Colorado clinicians of this cluster and requesting reports of similar cases. One additional case with similar neurologic findings was reported and is currently under investigation, the MMWR report said.

As of Oct. 8, there have been two additional cases of acute myelitis, for a total of 11 cases at Children's Hospital Colorado, said AAFP Board Chair Jeff Cain, M.D., who is chief of family medicine at the Denver hospital.

Similar to the current outbreak of enterovirus D68 (EV-D68) infection, which has spread far beyond its origins in the Midwest, these neurologic incidents are not unique to Colorado, and the possibility of a link between the two ailments is currently being examined by the CDC.

Story highlights
  • According to the CDC, 17 cases of acute neurologic illness have been verified in children in 12 states as of Oct. 8.
  • In each case, patients had experienced febrile illness, often associated with upper respiratory symptoms, within three to 16 days before the onset of neurologic symptoms.
  • Patients with the symptoms described should be referred immediately to a pediatric neurologist and/or a pediatric infectious disease specialist.

During a CDC Clinical Outreach and Communication Activity call( on Oct. 3, one after another, doctors around the country described the same neurologic illness with limb weakness that has been seen in Colorado.

According to an investigation update( from the National Center for Immunization and Respiratory Diseases, the CDC had verified reports of 17 cases in 12 states that meet the case definition of the illness as of Oct. 8.

To meet the case definition of the illness, a patient must satisfy all of the following criteria:

  • be age 21 or younger,
  • experience acute onset of focal limb weakness,
  • have symptoms that occurred on or after Aug. 1, and
  • have an MRI showing a spinal cord lesion largely restricted to gray matter.

Physicians with patients who meet the case definition should contact their state and local health departments, according to the CDC.

Description of Findings

According to the MMWR report, many of the patients with neurologic illness at Children's Hospital Colorado presented with neck, back or extremity pain, but otherwise had normal sensation in their limbs.

Seven of eight patients who had an MRI of the spinal cord displayed nonenhancing lesions of the gray matter that spanned multiple levels, and seven of nine who had an MRI of the brain had nonenhancing brainstem lesions (most commonly the dorsal pons).

Two of five patients who had an MRI of the lumbosacral region had gadolinium enhancement of the ventral nerve roots of the cauda equina. Eight patients demonstrated a mild to moderate cerebrospinal fluid (CSF) pleocytosis that was predominantly lymphocytic, which would be consistent with an inflammatory or infectious process, the report said.

Six of eight initial nasopharyngeal specimens obtained from the children were positive for rhinovirus/enterovirus and were typed: four were identified as EV-D68, one as rhinovirus A24 and one was not EV-D68 but has not been typed further. The specimen positive for rhinovirus A24 also was positive for adenovirus.

In previous studies on EV-D68, including a report in a 2006 MMWR Surveillance Summary,( there have been only two reported cases connecting the virus to neurologic illness (acute flaccid paralysis and encephalomyelitis) through detection in CSF, according to the Oct. 3 MMWR report.

"However, given the current suspected widespread circulation of EV-D68 respiratory infections in Colorado and the antecedent respiratory illness in most of these children, the detection of EV-D68 in nonsterile, upper respiratory tract specimens in those with neurologic illness might be coincidental," the report said. The agency is continuing its epidemiologic and laboratory investigations of these cases.

Course of Action

Patients with the described symptoms (acute viral syndrome followed by unexplained motor deficits) should be referred immediately to a pediatric neurologist and/or a pediatric infectious disease specialist, Cain said.

"These children will need an MRI and possibly an electromyogram," he said. "Supportive care with physical therapy and/or rehabilitation therapy is important for the best outcomes, as well."

After the child's initial care and subsequent referral to a specialist, it's important for family physicians to alert their local and/or state health departments of the potential case so that the information can, in turn, be reported to the CDC.

To facilitate that process, the agency is offering an online patient form( that the physician or the health department can fill out and send to

Clinicians should understand that myelitis stemming from EV-D68 is still a relatively rare occurrence and that there are other, more common causes of myelitis, Cain noted.

"For the vast majority of children, enterovirus D68 presents with common viral symptoms that are cleared within days by their normal immune response," he said. "The most common adverse outcome of EV-D68 continues to be respiratory complications with patients that have a history of asthma or chronic lung disease."

Related AAFP News Coverage
Growing Enterovirus Outbreak Ensnaring Children, Teens
Patients With Underlying Respiratory Problems Most at Risk, FP Expert Warns


Additional Resource
CDC: Unexplained Paralysis Hospitalizes Children(