National study on pediatric acute encephalopathy in Japan (April 2020 to October 2023): Insights from the third study

Previous national studies of acute encephalopathy in Japan were conducted in 2007-2010 and 2014-2017. In this third study (April 1, 2020-October 31, 2023), spanning the coronavirus disease 2019 (COVID-19) outbreak, we compared results to assess trends in pediatric viral infections and therapeutic practices.

Questionnaires were sent to 430 hospitals of the Japanese Pediatric Society, yielding 241 responses and 1197 cases. A secondary survey to 151 facilities received 110 responses (72.8 %), identifying 622 eligible patients (604 for treatment, 544 for outcome analysis). Data on patient background, syndrome classification, causative virus, treatment, and prognosis were collected.

Among 622 cases (54.6 % boys), the highest incidence was in 1-year-olds, with case numbers peaking during COVID-19 and influenza outbreaks. The frequency of clinical syndromes was: acute encephalopathy with biphasic seizures and late reduced diffusion, 35.1 %; clinically mild encephalitis/encephalopathy with a reversible splenial lesion, 17.8 %; hemorrhagic shock and encephalopathy syndrome (HSES), 6.9 %; acute encephalitis with refractory, repetitive partial seizures, 3.7 %; acute fulminant cerebral edema (AFCE), 2.2 %; acute necrotizing encephalopathy, 1.6 %; and unclassifiable, 31.4 %. Notably, the combined HSES/AFCE rate increased from 1.9 % in the 2014-2017 survey to 9.1 %, likely due to enhanced diagnosis and COVID-19 impact. Pathogens were exanthem subitum (16.1 %), severe acute respiratory syndrome coronavirus 2 (15.9 %), and influenza (7.7 %). Treatments included steroid pulse therapy (68.9 %), mitochondrial cocktails (42.5 %), and targeted temperature management (31.0 %).

This study provides a comprehensive overview of pediatric acute encephalopathy during COVID-19 outbreaks, shows increases in the incidence of HSES/AFCE, and presents current treatment.