Encephalopathy in Children Who Died of Influenza, 2010–2025

By Amara Fazal, Katie Reinhart, Stacy Huang, Krista Kniss, Samantha M. Olson, Vivien G. Dugan, Sascha Ellington, Alicia P. Budd, Carrie Reed, Timothy M. Uyeki and Shikha Garg, Influenza Division, CDC

At a glance

• What prompted this: in late January 2025, public health partners told CDC of critically ill children with influenza-associated encephalopathy or encephalitis (IAE), including several deaths from acute necrotizing encephalopathy (ANE), its most severe form.
• What CDC found: among child flu deaths from the 2010–11 through 2024–25 seasons, a median of 9% had IAE. In 2024–25 (through February 8, 2025), it was 13% — nine of 68 — including four with ANE.
• What it can't say: with no national surveillance for IAE, nobody knows whether this season's cases are more than expected.
• What to do: clinicians should consider IAE in children with flu and abnormal neurologic signs. Flu vaccination is recommended for everyone 6 months and older while flu viruses circulate.

What IAE is

Children of all ages — especially those under 5 with certain medical conditions — can suffer severe or fatal complications of flu, including pneumonia, myocarditis, pericarditis and neurologic complications (1).

• IAE is a range of neurologic syndromes set off by flu infection of the respiratory tract. The body's inflammatory response goes awry, causing varying degrees of brain dysfunction, inflammation, or both (2,3).
• ANE is one of the most severe forms of encephalopathy. It can follow flu and other viruses, including SARS-CoV-2 and human herpesvirus 6 (3). It is diagnosed from symmetric lesions in both thalami and other parts of the brain on a CT or MRI scan, in a child with a fever before or during the onset of neurologic symptoms and rapid neurologic decline.

How CDC looked

Influenza-associated deaths in children — under 18, with lab-confirmed flu and a compatible illness, and no complete recovery before death — have been nationally notifiable since 2004. Health departments report each to CDC's Influenza-Associated Pediatric Mortality Surveillance System on a standard form covering demographics, lab results, underlying conditions, clinical course, complications and vaccination.

• IAE: counted wherever the form's encephalopathy or encephalitis checkbox was marked.
• ANE: the form does not ask about it, so for 2024–25 CDC contacted state health departments to learn whether any child flu death with IAE had also been diagnosed with ANE.

What CDC found

Every season since 2010–11

Of 1,840 child flu deaths, 166 (9%) had IAE — from 0% (2020–21, when there was 1 death, as flu activity was historically low during the COVID-19 pandemic) to 14% (2011–12).

By age: IAE was most common among children 2–4 years (34 of 334, 10%) and least common among infants under 6 months (8 of 148, 5%).

The 166 children with IAE

• Age: median 6 years (IQR 2.5–10.5); 52% girls.
• Race and ethnicity: 40% non-Hispanic White, 28% Hispanic or Latino, 13% Black, 12% Asian or Pacific Islander.
• Virus: 72% influenza A, 28% influenza B. Of 73 A viruses subtyped, 56% were A(H1N1)pdm09 and 44% A(H3N2).
• Health: 54% had no underlying medical conditions.
• Vaccination: only 20% had received at least one dose of that season's flu vaccine more than 2 weeks before falling ill.
• Treatment: 73% received flu antivirals; 93% needed mechanical ventilation.
• Other complications: acute respiratory distress syndrome (34%), pneumonia (33%), sepsis (28%).
• Where they died: 96% in the hospital, 2% in the emergency department, 2% outside a hospital.

The four ANE deaths of 2024–25

• Reported: two by state health departments on their own; two more found when CDC contacted the states.
• All four: under 5, with lab-confirmed A(H1N1)pdm09, and all on mechanical ventilation.
• One had underlying medical conditions.
• Two had been vaccinated more than 2 weeks before falling ill; the other two had not been vaccinated that season.
• Two received oseltamivir; two had seizures in the hospital.

What it means

Is this season unusual? It can't be told. On February 24, 2025, CDC posted a national call on the Epidemic Information Exchange (Epi-X) for possible cases of child IAE this season (October 1, 2024, through May 30, 2025). Clinicians can start reporting at severeflu@cdc.gov — without sending any case details or protected health information by email.

Elsewhere: in Japan, where encephalopathy and encephalitis from infection are notifiable, 64 to 105 cases a season were reported in 2010–2015 across all ages; 74% were under 18, and 8% of those children died (4).

Kinds of IAE

1. ANE — the most severe, with high rates of death and lasting neurologic damage.
2. Acute encephalopathy with biphasic seizures and late reduced diffusion — an MRI finding that usually means tissue damage.
3. Clinically mild encephalitis or encephalopathy with a reversible splenial lesion (2).

Less often: acute encephalopathy with refractory partial seizures, and posterior reversible encephalopathy syndrome (2). There is no standard case definition for IAE yet, though consensus definitions for infection-triggered encephalopathy have recently been published (3).

Signs that point to IAE

Useful for surveillance or diagnosis, with clinical judgment (3–5):

1. age under 18;
2. lab-confirmed flu;
3. diagnosed encephalopathy or encephalitis, or neurologic signs lasting more than 24 hours — seizures, altered mental status, delirium, reduced consciousness, lethargy, hallucinations or personality changes;
4. brain imaging changes — swelling, inflammation or lesions — or an abnormal EEG (not always present);

with no other known cause.

Treatment

IAE can progress to severe impairment and death quickly after flu symptoms begin, so prompt recognition and care are crucial — including neurocritical care for raised pressure in the skull and management of multiorgan failure.

• Antivirals: recommended early for children at higher risk of flu complications, though whether they help in IAE is unknown. One study linked oseltamivir to a lower risk of neuropsychiatric events in flu patients (6).
• Other treatments used, without international evidence-based guidelines: high-dose pulse methylprednisolone, plasma exchange, therapeutic hypothermia, and immune therapy such as gamma globulin, anakinra and tocilizumab (6–8).
• A caution: in one study, the anti-inflammatory diclofenac sodium — but not acetaminophen — was linked to higher mortality in IAE (5).

More research is needed on how best to treat it.

Limitations

1. IAE was taken from a checkbox, which may over- or underestimate it.
2. The 2024–25 numbers are preliminary and small.
3. Deaths are not representative of all child IAE, especially milder cases.
4. Without established surveillance, it could not be said whether this season's reports are within or above the expected range.

For clinicians

• Consider IAE in children with fever and neurologic signs lasting more than 24 hours; consider ANE when there is also rapid decline and imaging shows symmetric lesions of both thalami.
• Test for flu and other viruses; get brain imaging.
• Start antivirals early if flu is confirmed or suspected — don't wait for lab confirmation.
• Provide supportive critical care as needed.
• Report possible cases to severeflu@cdc.gov. Standard criteria and a reporting route would show how common and serious IAE really is.
• Recommend vaccination strongly: flu activity is elevated and may continue into spring. Everyone eligible 6 months and older not yet vaccinated this season should be (9).

Sources

Based on Amara Fazal, Katie Reinhart, Stacy Huang, Krista Kniss, Samantha M. Olson, Vivien G. Dugan, Sascha Ellington, Alicia P. Budd, Carrie Reed, Timothy M. Uyeki and Shikha Garg, "Reports of Encephalopathy Among Children with Influenza-Associated Mortality — United States, 2010–11 Through 2024–25 Influenza Seasons," MMWR, Centers for Disease Control and Prevention; a work of the United States government in the public domain. Numbers in parentheses refer to the report's references.