Influenza A-Associated Acute Necrotizing Encephalitis With Complete Recovery in 19-Month-Old

Researchers describe a case of a previously healthy 19-month-old female who experienced rapid neurological deterioration following infection with influenza A (H1N1) and was found to have neuroimaging features characteristic of acute necrotizing encephalitis (ANE), including bilateral thalamic involvement and additional multifocal, symmetric gray- and white-matter lesions. Despite an unfavorable ANE severity score of 6, historically associated with high mortality, the patient demonstrated a complete neurological recovery following multimodal immunomodulatory therapy.

The patient, from Minnesota, was up to date on routine childhood immunizations with the exception of influenza and COVID-19 vaccines. Several days prior to admission, she developed respiratory symptoms concurrent with multiple family members who tested positive for influenza, and she did not receive any antiviral treatment. On the day prior to admission, she developed a new fever and associated fatigue. On the morning of admission, she experienced a witnessed seizure characterized by stiffening, arching movements, and subsequent unresponsiveness. Initial examination revealed a Glasgow Coma Scale score of 3 with ongoing seizure-like activity, and she was determined to have been in status epilepticus for at least an hour prior to arrival. She was hypoxemic (O2 saturation 84%) and febrile to 108 °F (rectal). She was intubated for airway protection, external cooling was initiated, and she received a loading dose of levetiracetam. Blood and urine cultures were obtained, and empiric therapy with ceftriaxone and vancomycin was initiated for possible bacterial meningitis. A blood HSV polymerase chain reaction was ultimately negative, and empiric acyclovir was started.

In the pediatric intensive care unit, the patient was treated in a stepwise manner with multimodal immunomodulatory therapy, including intravenous immunoglobulin (days 1-2), corticosteroids (start day 1), IL-1 receptor antagonist anakinra (start day 2), and plasma exchange (start day 3). Blood cytokine levels declined rapidly with initiation of immunomodulatory therapy. At initial presentation, multiple proinflammatory cytokines were markedly elevated in the peripheral blood; IL-6 and IL-8 levels were substantially higher in cerebrospinal fluid (590 and 1330 pg/ml, respectively) than in serum (118 and 68.2 pg/ml, respectively), providing insights into disease pathogenesis and central nervous system-specific immune activation.

The case was identified in the setting of heightened awareness following a CDC alert. In January 2025, the Centers for Disease Control and Prevention received reports of nine deaths in children due to severe influenza-associated encephalopathy and requested clinician and health department reporting of similar cases on February 28, 2025. The authors highlight the importance of early recognition of ANE in young children with recent influenza infection, the need for prompt multidisciplinary management, consideration of targeted immunomodulatory therapy, and further investigation of cytokine profiling as a tool to improve diagnosis and guide treatment.