Higher-dose methylprednisolone improves neurologic outcomes in ANE

Neurological outcomes are significantly improved by a combination of tocilizumab and 30 mg/kg/d) methylprednisolone (MP) vs 20 mg/kg/d) in pediatric acute necrotizing encephalopathy (ANE), according to a recent study published in Pediatric Investigation.¹

Traditionally, high-dose corticosteroids such as MP, intravenous immunoglobulin (IVIG), and tocilizumab are used to treat ANE.² However, the effectiveness of this treatment may vary based on the corticosteroid dosing, with limited data comparing 30 mg/kg/d vs 20 mg/kg/d.

“There are no studies directly comparing the high doses of MP to clinical outcomes in children with ANE, and the dosing remains unstandardized. Thus, our study may inform standardized immunotherapy protocols for this life-threatening condition,” said Suyun Qian, MD, honorary director of Beijing Children’s Hospital’s pediatric intensive care unit (PICU).²

Study design and patient population

The retrospective cohort study was conducted from January 2023 to January 2025 at Beijing Children’s Hospital.¹ Participants included pediatric patients aged 29 days to 18 years diagnosed with ANE and receiving combination therapy with high-dose MP pulse and tocilizumab.

ANE was diagnosed based on neuroradiological findings and criteria from Mizuguchi et al. Patients in the PICU for less than 24 hours were excluded from the analysis. Participants were stratified into a 20-mg/kg/d group and a 30-mg/kg/d group.¹

Investigators obtained data on participant demographics, clinical manifestations, laboratory examination results, therapeutic schedules, and clinical outcomes. Laboratory examination results were collected at PICU admission and 3 days after treatment. Additionally, investigators performed cranial imaging and etiological tests.¹

Treatment protocol and monitoring

Conventional treatments, organ support, and immunomodulation were included in immunization schedules. Patients received MP therapy for 3 days, followed by 7 to 10 days of tapering. The dose of tocilizumab was determined by a patient’s body weight, while IVIG was provided at a dose of 1 g/kg/d for 2 days.¹

Treatment-related adverse effects were reported to determine the safety of treatment combinations. Neurologic function was assessed during outpatient visits or telephone interviews using the Pediatric Overall Performance Category scale, with a score of 4 or greater indicating severe neurological sequelae.¹

Baseline characteristics and severity of illness

There were 23 patients included in the analysis, 11 of whom received 20 mg/kg/d MP and 12 received 30 mg/kg/d MP. Similar baseline characteristics were reported between groups, with a median time between prodromal symptoms and encephalopathy of 36 hours. Five cases of genetic mutations and 1 case of developmental delay were reported.¹

Of participants, 78.3% were critically ill at admission, 56.5% were in a deep coma, and 91.3% had multiple organ dysfunction syndrome. These rates did not significantly differ between groups.¹

All patients had respiratory pathogens, including influenza A in 69.6%, COVID-19 in 13%, Mycoplasma pneumoniae in 8.7%, human herpes virus in 4.3%, and influenza B in 4.3%. A significant reduction in procalcitonin levels was reported in the 30 mg/kg/d group, at 18.5 on day 1 vs 0.1 on day 3 ng/mL.¹

Laboratory findings and immunotherapy timing

Cerebrospinal fluid (CSF) protein and CSF cytokines also significantly decreased in this group, at 1682 mg/L and 632 pg/mL, respectively, on day 1 vs 441.5 mg/L and 81.5 pg/mL, respectively, on day 3. The 20-mg/kg/d group had comparable reductions in these markers. No significant changes in serum cytokine levels were reported in either group.¹

Immunotherapy was provided to all patients within 24 hours of PICU admission, with 95.7% receiving MP treatment within 72 hours of encephalopathy onset. All patients also received tocilizumab, and 34.8% needed a second dose after 1 week. Mechanical ventilation was required in 91.3%.¹

Utilization rates for adjunctive therapies were comparable between groups, at 91.3% for antivirals, 100% for IVIG, and 47.8% for therapeutic hypothermia. Overall, this data highlighted a combination of tocilizumab, high-dose MP, and IVIG as safe and effective for pediatric ANE.¹

“Our findings demonstrate that higher initial MP dose is associated with improved neurological outcomes, warranting further prospective, large-scale, multicenter studies to confirm these findings and help establish an optimal treatment protocol for this rare but fatal condition,” said Qian.

References

1. Li F, Li K, Fan C, Wang Q, Qian S. Effectiveness and safety of tocilizumab combined with different high-dose methylprednisolone regimens for acute necrotizing encephalopathy in children. Pediatr Investig. Published online January 27, 2026. doi:10.1002/ped4.70039
2. Pediatric investigation study evaluates the efficacy of tocilizumab with high-dose methylprednisolone for acute necrotizing encephalopathy. News release. Pediatric Investigation. February 12, 2026. Accessed February 17, 2026. https://www.eurekalert.org/news-releases/1116344