Acute necrotizing encephalitis as a catastrophic manifestation of influenza A in an immunocompetent adult

Influenza-associated neurological complications range from mild confusion to severe encephalopathy. Acute necrotizing encephalopathy, though rare, is increasingly reported in adults. Reviews estimate its incidence at ~0.21% in children with influenza, with adult cases underrecognized and associated with high morbidity and mortality.(¹,²) Thalamic lesions are most frequent (91%), and the adult case fatality rate reaches 32%.(¹) Several therapeutic strategies have been reported, including antivirals, corticosteroids, immunoglobulins, plasmapheresis, and interleukin (IL) 6 inhibitors such as tocilizumab.(¹) We report a rare neurological complication of influenza A in an adult, underscoring its diagnostic and therapeutic complexity.

A 52-year-old woman with asthma and allergic rhinitis presented with 3 days of flu-like symptoms, followed by sudden behavioral changes, altered speech, and gait instability. Neurological findings included obnubilation, ophthalmoparesis, bulbar dysfunction, ataxia, dystonia, spasticity, and hyperreflexia. She developed respiratory failure, requiring intensive care unit (ICU) admission. Her Simplified Acute Physiology Score (SAPS) II and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were 61 and 25, respectively. Brain magnetic resonance imaging showed findings compatible with rhombencephalitis (Figure 1). A nasal swab tested positive for influenza A.

Figure 1
Brain magnetic resonance imaging performed 7 days after admission to the neurointensive care unit (8 days after onset of neurological symptoms), with follow-upscans at 2 weeks and 1 month.

Lumbar puncture revealed raised opening pressure, high protein (226mg/dL), normal cell counts and no glucose consumption (glucose 60% of serum level). Cerebrospinal fluid bacterial culture, polymerase chain reaction (PCR) for influenza A and B, and anti-neuronal antibody testing were all negative. HIV, HBV, and HCV serologies were negative. Multiplex PCR for pathogens including Listeria monocytogenes, Borrelia burgdorferi, and Toxoplasma gondii was also negative. Protein electrophoresis showed a monoclonal gamma peak, likely related to prior intravenous immunoglobulin. Autoimmune testing revealed antinuclear antibody 1:160 (mottled), anti-Sjögren's-syndrome-related antigen A autoantibodies, and anti-Ro52 positivity; the remaining autoimmune encephalitis panel, including anti-N-methyl-D-aspartate receptor, was negative.

Acute necrotizing rhombencephalitis, likely autoimmune mediated in the context of post-viral inflammation, was assumed.

Due to intracranial hypertension, she was transferred to a neurocritical ICU. Treatment included a 5-day course of oseltamivir 150mg twice daily, methylprednisolone 1g, and intravenous immunoglobulin 60g, for 3 days. No further lumbar punctures were performed due to clinical stability and the absence of invasive intracranial pressure monitoring. After nine plasmapheresis sessions (membrane-based, using 1L of 5% albumin and 1.5L of fresh frozen plasma, without complications), no neurological improvement was observed. A multidisciplinary team initiated off-label tocilizumab 400mg single dose. Gradually, she improved clinically and radiologically (Figure 1). IL-6 levels, measured 26 days post-administration, were elevated (48.1pg/mL; ref < 6.4pg/mL), but normalized after 2 months (4.1pg/mL); no baseline value was available. She was discharged to a high-dependency unit after 72 ICU days. Despite complications (bacteremia from nosocomial pneumonia, oral candidiasis, and tracheobronchitis) no other organ dysfunctions occurred.

Influenza may cause complications ranging from mild illness to severe neurological involvement. Acute necrotizing encephalopathy, though rare, is among the most severe, and increasingly recognized in adults.(¹)

Acute necrotizing encephalopathy was first described by Mizuguchi in 1995(³) and is characterized by rapid neurological decline, seizures, coma. Lesions typically affect the thalami, brainstem, and cerebellum bylaterally.(⁴) Although direct viral invasion has been proposed, most evidence supports a cytokine-mediated mechanism involving blood-brain barrier disruption, vasogenic and cytotoxic edema, and in some cases, hemorrhage or necrosis.(⁵) Cerebrospinal fluid findings are usually non-specific, with elevated protein and normal or mildly elevated cell counts.(³,⁶) Elevated IL-6 levels have been reported and are proposed as a potential therapeutic biomarker.(¹,⁷)

In our case, neuroimaging revealed T2/FLAIR hyperintensities affecting the brainstem and thalami, with associated hemorrhagic and cytotoxic components, consistent with necrotizing rhombencephalitis. Influenza A was detected in a nasal swab, while cerebrospinal fluid PCR was negative - consistent with previous reports,(⁸,⁹) suggesting a para-infectious, immune-mediated mechanism rather than direct viral invasion. Despite its atypical presentation, we believe this case represents an autoimmune-mediated necrotizing rhombencephalitis secondary to influenza A.

Management of acute necrotizing encephalopathy remains challenging. While supportive care is essential, early immunomodulatory treatment is increasingly advocated. Our patient received a combination of high-dose oseltamivir (150mg twice daily), intravenous methylprednisolone, intravenous immunoglobulin, plasmapheresis,(¹⁰) and ultimately, tocilizumab. High-dose oseltamivir is used in severe cases, despite limited supporting evidence.(⁶,⁸) Tocilizumab, an IL-6 receptor antagonist, is a promising alternative in isolated reports, especially in patients with elevated IL-6 and poor response to first-line therapies.(¹,¹¹) Her improvement was likely multifactorial, reflecting the combined effect of antiviral and sequential immunotherapies. Acute necrotizing encephalopathy prognosis is variable, with adult mortality reaching 30 - 40%. Early diagnosis and timely, multimodal treatment may improve outcomes.

• Publisher's note
• ETHICS COMMITTEE APPROVAL
  Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos (N° 0030/CES/JAS).

AVAILABILITY OF DATA AND MATERIALS

The contents underlying the research text are included in the manuscript.

REFERENCES

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Edited by

• Responsible Editor:
  Thiago Costa Lisboa https://orcid.org/0000-0003-4306-2212

Publication Dates

• Publication in this collection
  12 Dec 2025
• Date of issue
  2025

History

• Received
  01 Feb 2025
• Accepted
  10 July 2025