Influenza-Associated Acute Necrotizing Encephalopathy: An Illustrative Case Amidst the Severe United States 2024-25 Influenza Season

Acute necrotizing encephalopathy (ANE) is a rare, fulminant encephalopathy associated with viral infections, such as influenza, characterized by multifocal symmetric brain lesions and cytokine-mediated neuroinflammation. A 6-year-old previously healthy female, fully vaccinated except for the seasonal influenza vaccine, presented with fever, sore throat, cough, and worsening altered mental status. Neurological examination revealed a Glasgow Coma Scale (GCS) of 6, abnormal brainstem reflexes, and subsequent seizure activity, ultimately necessitating intubation. Initial laboratory findings were notable for hyperglycemia, ketonuria, and elevated cerebrospinal fluid (CSF) protein, while brain magnetic resonance imaging (MRI) demonstrated characteristic bilateral thalamic, brainstem, and cerebellar lesions. Continuous electroencephalography (EEG) showed diffuse slowing without epileptiform discharges. Empirical treatment included broad-spectrum antibiotics, antiviral therapy (oseltamivir), high-dose corticosteroids, and intravenous immunoglobulin (IVIg). The patient required prolonged ventilatory support and experienced significant motor dysfunction, hypertonicity, and disorder of consciousness for approximately one month. A follow-up MRI showed evolving encephalomalacia and atrophy, particularly in the frontal lobes, hippocampi, and basal ganglia. After a subsequent month of inpatient rehabilitation, she demonstrated substantial functional improvement, regaining the ability to walk short distances with assistance, communicate verbally, and resume oral feeding. However, persistent deficits in cognitive processing speed, problem-solving, vision, and motor control remained. This case highlights the severity of influenza-associated ANE and its potential for lasting neurological impairment. Although no standardized treatment protocol exists, immunomodulatory therapies such as corticosteroids and IVIg are widely used based on the presumed role of cytokine dysregulation. Early recognition and aggressive supportive care are critical in ANE management. Intensive neurorehabilitation plays a key role in optimizing functional outcomes, though long-term deficits may persist. This case brings up key and timely questions about the importance of influenza vaccination in preventing severe neurological complications. Notably, anecdotal reports indicate increased cases of influenza-associated encephalopathy in recent flu seasons, emphasizing the need for heightened clinical awareness and further research into prognostic markers and treatment strategies.