High-dose methylprednisolone and tocilizumab improve
survival of patients with high-risk pediatric acute
necrotizing encephalopathy

Fan, Chaonan; Li, Fei; Li, Kechun; Li, Zheng; Mao, Yiyang; Wang, Lijuan; Liu, Gang; Liu, Yingchao; Wang, Quan; Qian, Suyun

doi:.0.0.0

Original Article

DOI: https://doi.org/10.3345/cep.2025.01431 [Accepted]
Published online October 22, 2025.

High-dose methylprednisolone and tocilizumab improve survival of patients with high-risk pediatric acute necrotizing encephalopathy

Chaonan Fan

Department of Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China

Correspondence:
Suyun Qian, Email: syqian2020@163.com

Received: 27 June 2025 • Revised: 28 July 2025 • Accepted: 6 August 2025

Abstract

Background
Acute necrotizing encephalopathy (ANE) is a rare but devastating neurological disorder in children that is typically triggered by viral infections such as influenza, sudden acute respiratory syndrome coronavirus 2, and human herpesvirus-6. ANE is characterized by cytokine storm and associated with high mortality; however, optimal immunomodulatory strategies remain undefined.
Purpose
To evaluate the effectiveness of multiple immunomodulatory strategies, including high-dose methylprednisolone (MP), plasma exchange (PLEX), and tocilizumab, at reducing short-term mortality among pediatric patients with ANE stratified by disease severity using the ANE severity score (ANE-SS).
Methods
We retrospectively reviewed 65 pediatric patients (median age, 4.8 years; interquartile range, 2.8–7.7 years) diagnosed with ANE at Beijing Children’s Hospital from 2016 to 2024. Patients were stratified by ANE-SS at admission into low- to medium-risk (ANE-SS<5) and highrisk (ANE-SS≥5) groups. Immunomodulatory treatments included different doses of MP, intravenous immunoglobulin, PLEX, and tocilizumab. The primary outcome was the 28-day postdischarge mortality. Multivariate logistic regression was used to identify the treatment strategies that were independently associated with improved survival.
Results
The overall 28-day postdischarge mortality rate was 45.9%, significantly higher in patients with ANE-SS ≥5 (65.7%) than in those with ANE-SS<5 (16.7%; P<0.001). A notable decline in mortality has been observed since 2022, coinciding with the increased use of high-dose MP (20 and 30 mg/kg/day) and tocilizumab. The annual mortality rate will drop to 38.9% in 2022, 36.8% in 2023, and 16.7% in 2024. In low- to medium-risk patients (ANE-SS<5), both 20- mg/kg/day and 30-mg/kg/day MP were associated with improved outcomes. In high-risk patients (ANE-SS≥5), the combination of 30-mg/kg/day MP and tocilizumab provided the greatest survival benefit. Multivariable logistic regression analysis identified that this combined therapy was independently associated with reduced mortality (odds ratio, 0.04; 95% confidence interval, 0.01–0.18; P< 0.001). No significant survival benefit was observed following PLEX treatment.
Conclusion
In low- to moderate-risk patients, the 20- and 30-mg/kg/day MP regimens were effective. In highrisk patients with ANE, high-dose MP (30 mg/kg/day), particularly when combined with tocilizumab, may improve survival and possibly long-term neurological recovery. These findings support the use of a severity-based immunotherapy strategy for pediatric patients with ANE.

Key Words: Acute necrotizing encephalopathy, Immunotherapy, Tocilizumab, Methylprednisolone, Mortality, Children