Pathogenesis and Management of Acute Necrotizing Encephalopathy

Qin, Ningxiang; Wang, Jing; Peng, Xi; Wang, Liang

doi:10.1080/14737175.2023.2224503

Cited by 11 publications

(6 citation statements)

References 90 publications

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“…Numerous studies have indicated that infection is a common triggering factor for ANEC. Various pathogens, like influenza viruses, human herpesviruses, and enteroviruses, have been found in ANEC patients and are associated with the onset of ANEC ( 2 ). Infection can activate the body’s immune system, leading to an excessive inflammatory response and neuronal damage.…”

Section: Discussionmentioning

confidence: 99%

“…ANEC primarily occurs in previously healthy children and causes progressive systemic inflammation and brain tissue necrosis. The pathogenesis of ANEC remains unclear; however, current theories suggest that viral infections, overactive immune response following infection, and genetic susceptibility may contribute to ANEC development ( 2 ). However, due to its rarity and the complexity of its pathogenesis, the understanding of ANEC is still limited internationally.…”

Section: Introductionmentioning

confidence: 99%

“…Typical symptoms include high fever, headache, altered consciousness, seizures, hypomyotonia, and brainstem dysfunction. According to case reports, most ANEC patients have three stages: prodromal infection, acute encephalopathy, and recovery ( 2 , 3 ). Children commonly have fever and acute respiratory or gastrointestinal symptoms in the prodromal stage, like cough, vomiting, and diarrhea.…”

Section: Introductionmentioning

confidence: 99%

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Clinical characteristics and prognostic analysis of acute necrotizing encephalopathy of childhood: a retrospective study at a single center in China over 3 years

Fang,

Gao,

Jin

et al. 2023

Front. Neurol.

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ObjectiveAcute Necrotizing Encephalopathy of Childhood (ANEC) is a rare, fulminant neurological disease in children with unknown mechanisms and etiology. This study summarized the clinical characteristics, treatment, and prognosis of ANEC through a retrospective analysis, providing insights into the ANEC early diagnosis and prognosis assessment.MethodsClinical data of children diagnosed with ANEC at the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University from July 1, 2020, to June 30, 2023, were retrospectively analyzed.ResultsThere were 25 cases, 14 males and 11 females, with a median age of 3 years. Hospital admissions were mainly in the winter (14/25, 56%) and spring (9/25, 36%). All patients presented with varying degrees of fever and altered consciousness, with 92% (23/25) experiencing high body temperatures (>39.1°C) and 88% (22/25) having a Glasgow coma scale (GCS) score of ≤8. Seizures were observed in 88% (22/25) of patients. Laboratory findings indicated 100% B lymphocyte activation (14/14), and 78% (14/18) of patients showed cytokine storm (interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-α). Neuroimaging showed symmetrical thalamus involvement, commonly involving basal ganglia and brainstem regions. Viral infection (23/24, 96%) was the predominant etiological finding, with 42% (10/24) of cases due to SARS-CoV-2 infection and 42% (10/24) to influenza A virus infection. Multi-organ dysfunction occurred in 68% (17/25) of patients, and 52% (13/25) died. Correlation analysis revealed the death group exhibited higher proportion of male, lower GCS scores, higher IL-6 level and a greater likelihood of associated brainstem impairment (p < 0.05).ConclusionANEC is more prevalent in the winter and spring, and its etiology may be associated with B lymphocyte activation and cytokine storm following viral infections. Clinical manifestations lack specific features, with fever, consciousness disturbances, and seizures being the main presentations, particularly in cases of high fever and hyperpyrexia. ANEC progresses rapidly and has a high mortality rate. The child’s gender, GCS score, IL-6 levels, and the presence of brainstem involvement can serve as important risk factors for assessing the risk of mortality.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical characteristics and prognostic analysis of acute necrotizing encephalopathy of childhood: a retrospective study at a single center in China over 3 years

Fang,

Gao,

Jin

et al. 2023

Front. Neurol.

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“…Although various hypotheses have been proposed, such as genetic susceptibility, direct invasiveness, dependent enhancement of vaccine‐related antibodies, and cytokine storm, the exact mechanisms are unclear. 28 Interestingly, recent studies found that SARS‐CoV‐2 affects the gene expression and function of RANBP2, 29 , 30 which might be involved in the pathogenesis of COVID‐19‐related ANE in patients with RANBP2 gene mutations. There is no evidence to support that SARS‐CoV‐2 is more likely to induce ANE than other viruses in RANBP2 mutation‐positive individuals.…”

Section: Discussionmentioning

confidence: 99%

Recurrent infection triggered encephalopathy syndrome in a pediatric patient with RANBP2 mutation and severe acute respiratory syndrome coronavirus 2 infection

Li,

Huo,

Wang

et al. 2023

Pediatric Investigation

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IntroductionAcute necrotizing encephalopathy (ANE), a fatal subtype of infection‐triggered encephalopathy syndrome (ITES), can be triggered by many systemic infections. RANBP2 gene mutations were associated with recurrent ANE.Case presentationHere we report a 1‐year‐old girl with recurrent ITES and RANBP2 mutation. She was diagnosed with influenza‐associated encephalopathy and made a full recovery on the first episode. After severe acute respiratory syndrome coronavirus 2 infection, the patient presented with seizures and deteriorating mental status. Brain magnetic resonance imaging revealed necrotic lesions in bilateral thalami and pons. Methylprednisolone, immunoglobulin, and interleukin 6 inhibitors were administered. Her consciousness level was improved at discharge. Nineteen cases of 2019 coronavirus disease‐related ANE have been reported, of which 22.2% of patients died and 61.1% had neurologic disabilities. RANBP2 gene mutation was found in five patients, two of whom developed recurrent ITES.ConclusionPatients with RANBP2 mutations are at risk for recurrent ITES, may develop ANE, and have a poor prognosis after relapse.

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“…The diagnostic criteria for ANE as originally established by Mizuguchi in 1995 remain unamended to date ( 5 ). We used the definition of ANE in this study as defined by Mizuguchi et al as follows: acute noninflammatory encephalopathy with an alteration in the level of consciousness; the demonstration by head computed tomography (CT) or magnetic resonance imaging (MRI) of bilateral symmetric thalamic lesions, other regions such as periventricular white matter, inner capsule, putamen, upper brainstem tegmentum, and cerebellar medulla can be involved; serum transaminase elevation but no hyperammonemia; CSF leucocyte count 8/mm 3 or less and the absence of any other reasonable explanation for the cerebral abnormalities ( 3 6 ).…”

Section: Methodsmentioning

confidence: 99%

Cytokine Storm Related to CD4⁺ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy

Wang,

Wang

et al. 2024

Immune Netw

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Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virus-associated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients’ CD4 + T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4 + T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.

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Pathogenesis and Management of Acute Necrotizing Encephalopathy

Cited by 11 publications

References 90 publications

Clinical characteristics and prognostic analysis of acute necrotizing encephalopathy of childhood: a retrospective study at a single center in China over 3 years

Clinical characteristics and prognostic analysis of acute necrotizing encephalopathy of childhood: a retrospective study at a single center in China over 3 years

Recurrent infection triggered encephalopathy syndrome in a pediatric patient with RANBP2 mutation and severe acute respiratory syndrome coronavirus 2 infection

Cytokine Storm Related to CD4⁺ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy

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Pathogenesis and Management of Acute Necrotizing Encephalopathy

Cited by 11 publications

References 90 publications

Clinical characteristics and prognostic analysis of acute necrotizing encephalopathy of childhood: a retrospective study at a single center in China over 3 years

Clinical characteristics and prognostic analysis of acute necrotizing encephalopathy of childhood: a retrospective study at a single center in China over 3 years

Recurrent infection triggered encephalopathy syndrome in a pediatric patient with RANBP2 mutation and severe acute respiratory syndrome coronavirus 2 infection

Cytokine Storm Related to CD4+ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy

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Cytokine Storm Related to CD4⁺ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy