Influenza Virus-Associated Fatal Acute Necrotizing Encephalopathy: Role of Nonpermissive Viral Infection?

Mungaomklang, Anek; Chomcheoy, Jiraruj; Wacharapluesadee, Supaporn; Joyjinda, Yutthana; Jittmittraphap, Akanitt; Rodpan, Apaporn; Ghai, Siriporn; Saraya, Abhinbhen; Hemachudha, Thiravat

doi:10.4137/ccrep.s40610

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…We proposed that the extremely high IL-6 level might be responsible for the formation of ANE without the involvement of the respiratory symptoms. This has been reported in 6-year-old-boy of influenza virus associated ANE without pulmonary involvement in Thailand which resembles what we found in our case [ 10 ].…”

Section: Discussionsupporting

confidence: 91%

COVID-19 related acute necrotizing encephalopathy with extremely high interleukin-6 and RANBP2 mutation in a patient with recently immunized inactivated virus vaccine and no pulmonary involvement

et al. 2022

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Background We report the first case of COVID-19 associated acute necrotizing encephalopathy (ANE) without pulmonary disease in a patient with an extremely high interleukin-6 (IL-6) level and Ran Binding Protein 2 (RANBP2) mutation. Case presentation A 29-year-old woman recently immunized with inactivated viral vaccine—BBIBP32-CorV (Sinopharm) presented with alteration of consciousness. Her body temperature was 37° Celsius, blood pressure 42/31 mmHg, heart rate 130 bpm, respiratory rate 20 per minute, and oxygen saturation 98%. Respiratory examination was unremarkable. Neurological examination revealed stupor but preserved brainstem reflexes. Non-contrast computerized tomography of the brain showed symmetrical hypodense lesions involving bilateral thalami and cerebellar hemispheres characteristic of ANE. No pulmonary infiltration was found on chest radiograph. SARS-CoV-2 was detected by PCR; whole genome sequencing later confirmed the Delta variant. RANBP2 gene analysis revealed heterozygous Thr585Met mutation. Serum IL-6 was 7390 pg/mL. Urine examination showed pyelonephritis. Her clinical course was complicated by seizure, septic shock, acute kidney injury, and acute hepatic failure. She later developed coma and passed away in 6 days. Conclusions ANE is caused by cytokine storm leading to necrosis and hemorrhage of the brain. IL-6 was deemed as a prognostic factor and a potential treatment target of ANE in previous studies. RANBP2 missense mutation strongly predisposes this condition by affecting mitochondrial function, viral entry, cytokine signaling, immune response, and blood–brain barrier maintenance. Also, inactivated vaccine has been reported to precipitate massive production of cytokines by antibody dependent enhancement (ADE). The true incidence of COVID-19 associated ANE is not known as were the predictors of its development. We proposed these potential two factors (RANBP2 mutation and ADE) that could participate in the pathogenesis of ANE in COVID-19 apart from SARS-CoV2 infection by itself. Further study is needed to confirm this hypothesis, specifically in the post-vaccination period. Role of RANBP2 mutation and its application in COVID-19 and ANE should be further elaborated.

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Section: Discussionsupporting

confidence: 91%

COVID-19 related acute necrotizing encephalopathy with extremely high interleukin-6 and RANBP2 mutation in a patient with recently immunized inactivated virus vaccine and no pulmonary involvement

et al. 2022

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“…12 The prevalence of the influenza A virus could explain the occurrence of acute necrotizing encephalopathy in influenza outbreak seasons, which was contributed by the role of nonpermissive infection as an alternative pathogenetic mechanism of the influenza virus. 14 In our case cohort, there was 1 case of acute necrotizing encephalopathy associated with the parainfluenza type 1 virus, which is rare, with 1 reported case in Korea 15 and 1 reported case in Hong Kong. 8 The laboratory abnormalities were diverse, and they usually peaked on the second day of presentation.…”

Section: Laboratory and Neuroimaging Findingsmentioning

confidence: 63%

Presentation and Outcome of Acute Necrotizing Encephalopathy of Childhood: A 10-Year Single-Center Retrospective Study From Hong Kong

Chow

2020

J Child Neurol

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Acute necrotizing encephalopathy (ANE) is a rare disease in childhood. We reviewed the 10-year data from a local pediatric department, reported the clinical characteristics, laboratory tests, neuroimaging findings, and outcome of the acute necrotizing encephalopathy cases and identified the potential factors affecting the outcome. Eight episodes of acute necrotizing encephalopathy among 7 patients were recorded, in which all of them had an initial presentation of fever and seizure. We identified that acute necrotizing encephalopathy patients with a severe score of Glasgow Coma Scale (GCS) on presentation, brainstem involvement in magnetic resonance imaging (MRI) of the brain, and higher MR imaging scores were associated with worse outcome. Association of outcome with acute necrotizing encephalopathy severity score, platelet count, and serum alanine aminotransferase level did not reach a statistically significant level. These results highlight the importance of combined clinical, laboratory, and neuroimaging findings in determining the prognostic outcome of acute necrotizing encephalopathy patients.

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“…ANE seems to develop secondary to a variety of different viruses including influenza virus and human herpesvirus 6 19202122232425. Etiologic agents in this study include novel influenza A (H1N1), Coxsackie virus A16, Mycoplasma pneumoniae, and herpes simplex virus (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Acute Necrotizing Encephalopathy in Children: a Long Way to Go

2019

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Background Acute necrotizing encephalopathy (ANE) is a rare, but potentially life threatening neurological condition in children. This study aimed to investigate its clinical spectrum, diagnostic and therapeutic dilemma, and prognosis. Methods Twelve children with ANE were included in the study. The diagnosis was made by clinical and radiological characteristics from January 1999 to December 2017 and their clinical data were retrospectively analyzed. Results A total of 12 children aged 6 to 93 months at onset (5 male: 7 female) were evaluated. The etiology was found in 4 of them (influenza A, H1N1; coxsackie A 16; herpes simplex virus; and RANBP2 gene/mycoplasma). The most common initial presentations were seizures (67%) and altered mental status (58%). The majority of the subjects showed elevation of aspartate aminotransferase/alanine aminotransferase with normal ammonia and increased cerebrospinal fluid protein without pleocytosis. Magnetic resonance imaging revealed increased T2 signal density in bilateral thalami in all patients, but the majority of the subjects (67%) also had lesions in other areas including tegmentum and white matter. Despite the aggressive immunomodulatory treatments, the long-term outcome was variable. One child and two sisters with genetic predisposition passed away. Conclusion ANE is a distinctive type of acute encephalopathy with diverse clinical spectrum. Even though the diagnostic criteria are available, they might not be watertight. In addition, treatment options are still limited. Further studies for better outcome are needed.

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Influenza Virus-Associated Fatal Acute Necrotizing Encephalopathy: Role of Nonpermissive Viral Infection?

Cited by 4 publications

References 17 publications

COVID-19 related acute necrotizing encephalopathy with extremely high interleukin-6 and RANBP2 mutation in a patient with recently immunized inactivated virus vaccine and no pulmonary involvement

COVID-19 related acute necrotizing encephalopathy with extremely high interleukin-6 and RANBP2 mutation in a patient with recently immunized inactivated virus vaccine and no pulmonary involvement

Presentation and Outcome of Acute Necrotizing Encephalopathy of Childhood: A 10-Year Single-Center Retrospective Study From Hong Kong

Acute Necrotizing Encephalopathy in Children: a Long Way to Go

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