Respiratory viral triggers and pediatric acute necrotizing encephalopathy: a systematic review and meta-analysis of risk, clinical phenotype, and outcomes.

Authors

Zhou Liang, Fei Long, Fengli Zheng, Zhi Jun Tan

Published in

Frontiers in neurology. Volume 17. Pages 1839145. Epub Oct 16, 2026.

Abstract

Acute necrotizing encephalopathy is a rare but severe pediatric neurological disorder characterized by rapid neurological deterioration and characteristic bilateral thalamic lesions on neuroimaging. Increasing evidence suggests that respiratory viral infections, particularly influenza viruses and SARS-CoV-2, play a major role in triggering ANE. However, clinical evidence remains fragmented due to the rarity of the disease. This study aimed to systematically synthesize current evidence on respiratory viral triggers, clinical presentation, neuroimaging features, treatment strategies, and outcomes of pediatric ANE.
A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. Electronic databases including PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched for studies published between January 1, 2015, and March 31, 2026 involving pediatric patients (<18 years) diagnosed with ANE associated with respiratory viral infections. Observational studies, case series, and case reports with extractable clinical data were included. Pooled descriptive analyses were performed to summarize demographic characteristics, viral triggers, clinical features, neuroimaging findings, therapeutic interventions, and outcomes.
Fifteen studies comprising 138 pediatric ANE cases were included. Most patients were previously healthy children, predominantly in early childhood. The most common viral triggers were influenza viruses (46.0%) and SARS-CoV-2 (42.3%), accounting for nearly 90% of cases. Clinically, fever (93.4%), altered consciousness (94.9%), and seizures (68.6%) were the most frequent manifestations. Neuroimaging consistently showed bilateral thalamic lesions (94.2%), often accompanied by brainstem (33.6%) or basal ganglia involvement (28.5%). Treatment commonly involved corticosteroids (75.9%) and intravenous immunoglobulin (51.8%), with some patients receiving targeted immunomodulatory therapies such as tocilizumab. Despite aggressive treatment, mortality remained substantial, with 54 deaths among 138 reported cases (39.1%). The random-effects pooled mortality estimate was 39.1% (95% CI: 29.8-49.8%).
Respiratory viral infections-particularly influenza and SARS-CoV-2 are major triggers of pediatric ANE. The disorder is characterized by rapid neurological decline and characteristic bilateral thalamic lesions, with substantial mortality and long-term neurological morbidity. Further multicenter prospective studies are needed to clarify immunopathogenesis and establish standardized therapeutic strategies to improve outcomes.

PMID:
42964027
Bibliographic data and abstract were imported from PubMed on 31 Oct 2026.

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