Influenza A-Associated Acute Necrotizing Encephalitis With Complete Recovery Following Early Immunomodulatory Therapy

We 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. At initial presentation, multiple proinflammatory cytokines were markedly elevated in the peripheral blood. Interestingly, while multiple cytokines were also elevated in cerebrospinal fluid (CSF), interleukin-6 (IL-6) and IL-8 levels were substantially higher in CSF (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 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. She demonstrated a favorable clinical response with complete neurological recovery, despite an unfavorable ANE severity score of 6 that has historically been associated with high mortality. This case highlights 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.