OBJECTIVE(S): Infection Triggered Encephalopathy Syndrome (ITES) is a rare but potentially severe complication of infections in children. ITES is a syndrome of acute encephalopathy that occurs in the context of a febrile illness and hypothesised to result from a cytokine mediated infection-triggered cytotoxicity in the central nervous system (CNS) without parenchymal inflammatory cell infiltration. ITES is considered distinct from infectious and immune-mediated encephalitis. We aimed to describe the demographics, associated pathogens, clinical spectrum and outcomes of ITES in Australian children from May 2013 until June 2024.
STUDY DESIGN: We extracted and analysed data from the prospective, multicentre Australian Childhood Encephalitis (ACE) study. Cases of ITES aged ≤14 years were reviewed and categorised by a multidisciplinary expert panel. We estimated the incidence for specific sub-types of ITES.
RESULTS: Of 1160 cases of Australian children with suspected encephalitis, 220 met criteria for ITES. In 83% (n=183) an associated pathogen was detected of which influenza (50%; n=109), enterovirus (8%; n=18), SARS-CoV-2 (COVID-19) (7%; n=15), and adenovirus (6%; n=13) were most common. The median age of affected children was 4.3 years (IQR 2-8.1). Of sub-types of ITES, the most frequent was Acute Necrotising Encephalopathy (ANE) (n=28, 13%), followed by Acute Encephalopathy with biphasic Seizures and late reduced Diffusion (AESD) (n=20, 9%), then Mild Encephalopathy with Reversible Splenial lesion (MERS) (n=21, 10%), although most children did not have a specific sub-type (n=135, 61%). For ITES sub-types, incidence was highest for ANE (0.82 per 1,000,000), and lowest for Febrile Infection Related Epilepsy Syndrome (FIRES, 0.23 per 1,000,000). Most children with ITES (60%; n=132) recovered fully. Poorer outcomes were seen in children diagnosed with ITES sub-types including ANE, AESD, and Acute Fulminant Cerebral Edema (AFCE).
CONCLUSION(S): ITES is an uncommon complication of common infections in Australian children. Influenza was the most frequently associated pathogen, with ANE the most frequent specific ITES sub-type. Outcomes are variable, but concerningly poor for some ITES sub-types including ANE.