Neurologic Complications of Flu in Kids May Be Up This Year

MedPage Today story.

Public health officials are looking into reports of a small potential uptick in neurologic complications of influenza in children -- particularly a rapidly progressing and dangerous condition called acute necrotizing encephalopathy (ANE).

Adrienne Randolph, MD, MSc, of Boston Children's Hospital, said she reported about 12 potential cases of flu-associated ANE to CDC's National Center for Immunization and Respiratory Diseases (NCIRD) in the past few weeks.

Randolph's position as the leader of the Pediatric Intensive Care Influenza Network gives her particular insight into what's happening with influenza complications in children across the country.

"There's not a study going on to say that these cases are all really acute necrotizing encephalopathy," Randolph told MedPage Today, urging caution about making preliminary conclusions. "That's why I informed the CDC about potential cases across the U.S. that I was made aware of. They can investigate."

She noted that ANE can be a complicated diagnosis to make, requiring certain clinical features as well as imaging findings. That's why "whatever is done needs to be done in a systematic way, where cases get looked at carefully by experts," she said.

Nonetheless, Randolph said she didn't recall any investigators from her sites observing any flu-related ANE cases last year.

A spokesperson for the CDC told MedPage Today that the agency "is aware of anecdotal reports" of influenza A-associated ANE in children. "We do not have active surveillance for ANE, but we are looking into the situation and will provide updates."

Randolph said her NCIRD contacts "asked me smart questions, and I sent them more information, and that's pretty much it."

A physician at one U.S. center told MedPage Today that their facility had a baby die of flu-associated ANE this year. "It progressed really rapidly and she [went into a coma] and passed away because of the complications of that," said the source, whose name and location have been withheld to protect patient privacy. The baby had been previously healthy.

Andrew Silverman, MD, MHS, and Keith Van Haren, MD, of Stanford Medicine in California, said they are aware of at least 10 cases of flu-associated ANE in their state alone over last year's and this year's influenza seasons.

"Although ANE is not a specifically reportable condition, this appears to be a true increase in the number of cases," Silverman told MedPage Today. Last year, they treated a child for flu-related ANE at Lucile Packard Children's Hospital Stanford, and published a case report in Neurology.

That case was followed by "an unusual cluster of additional cases within the next few weeks, prompting interest in a larger case series," Van Haren told MedPage Today.

Silverman and Van Haren are collecting cases of flu-associated ANE, and recently issued a request on the International Society of Infectious Diseases' ProMED email listserv. Silverman said that with the help of the California Department of Public Health, they also are requesting enhanced surveillance recommendations for the condition.

Symptoms of ANE can include seizures and altered mental status, and patients can become comatose, said Sue Hong Routson, MD, a pediatric neurointensivist at Johns Hopkins Children's Center in Baltimore.

"It's this type of fulminant cerebral edema where the brain swells so rapidly within a really short timeframe," Routson told MedPage Today. "A kid can walk into the hospital, and a day or two later, the brain is swollen so severely that they lose all their brain function. It's a pretty terrifying entity in that it feels once the dominoes start tipping, it's really hard to come back from it."

Classic imaging findings for ANE include bilateral thalamic involvement, deep gray matter involvement, and sometimes brain stem involvement, she said.

Routson said her facility has had one case of ANE this year, along with four other cases of children with neurologic complications from influenza that didn't have the classic ANE findings on MRI or the clinical progression.

Typically, she said she sees maybe one case of influenza with neurologic complications each year: "It does feel like we're seeing a lot more brain-related issues this year than I've seen in the past," she said.

She noted that it's "been a very active flu season" with "a lot of flu-related [intensive care unit] admissions" happening right now.

Indeed, CDC data show influenza is at an all-time high, surpassing even the H1N1 pandemic season of 2009-2010, a CDC source who requested anonymity told MedPage Today. "The percentage of outpatient visits that influenza-like illness comprises as of the week ending Feb. 1 is the highest it has ever been, including higher than the 2009 H1N1 pandemic," the source said.

It's not clear if an overall surge in influenza could be driving an increased number of rare complications, experts said. There's also the possibility of less vaccination, or perhaps less immunity as children may have been less exposed to influenza during the COVID-19 pandemic.

Last year, however, Italian researchers reported a flu outbreak with ANE at Meyer Children's Hospital in Florence, Italy. Seven children developed the condition, ranging from milder encephalopathy to ANE with coma and multiorgan failure, they detailed in the European CDC's journal, Eurosurveillance.

One of the children died and another was left in a minimally conscious state, while the rest did make a good or full recovery.

All of the children tested positive for the 2009 pandemic strain of H1N1, the authors reported, though it wasn't clear exactly what caused the cluster of cases.

Clinicians have been on the alert as H5N1 avian influenza spreads across dairy herds and poultry flocks throughout the U.S., with human cases reaching a total of 68, according to the latest CDC data.

However, Randolph noted that any potential increase in neurologic complications of flu this year does not seem to be tied to H5N1. Several of the 12 cases she reported to CDC did have subtyping, and they turned out to be the 2009 H1N1 pandemic strain, she said.

Nonetheless, sources at CDC said they feel like they're in the dark on influenza surveillance, as they have not been allowed to communicate with key partners such as medical organizations.

"Normally we would have communicated quite a bit with our clinical and other partners right now, but we can't talk to any of them because we have been ordered to stand down by the new executive branch administration," the source said.

When it comes to H5N1 in particular, the source said the CDC isn't getting sufficient information about testing or subtyping, "and therefore we don't understand the situation well."

Randolph and Routson said the treatment for ANE, since it's thought to be an overreaction of the immune system, includes steroids, intravenous immunoglobulin, and other immune modulators like anakinra (Kineret) and tocilizumab (Actemra).

They noted that getting the word out about a potential uptick in cases might help community physicians better identify and treat the condition.