Researchers reveal tocilizumab with high-dose methylprednisolone is associated with improved neurological outcomes in children with encephalopathy
Acute necrotizing encephalopathy (ANE) is a rare but life-threatening pediatric neurologic disorder characterized by rapid progression and high mortality. Tocilizumab, an interleukin-6 receptor antagonist, combined with high-dose methylprednisolone (MP, ≥20 mg/kg/day) may improve outcomes, yet the optimal MP dosing strategy remains uncertain. Now, researchers have evaluated the comparative efficacy and safety of two high-dose MP regimens (20 mg/kg/day vs. 30 mg/kg/day), each in combination with tocilizumab for ANE. The findings suggest that higher dose of MP may yield better neurological outcomes with no increase in adverse events in children with ANE.
ANE is a devastating parainfectious encephalopathy that is frequently associated with viral infections such as influenza and coronavirus disease 2019. The mortality rates among children range from 29.4% to 66.7%, with approximately 0-30% of patients surviving without neurological disabilities. Given the critical role of the "cytokine storm" and systemic hyperinflammation in its progression, immunomodulatory strategies are currently the primary therapeutic approach for ANE.
Therapeutic regimens for ANE typically include high-dose corticosteroids (e.g., methylprednisolone, MP), intravenous immunoglobulin (IVIG), and tocilizumab (a humanized antibody inhibiting the IL-6 receptor). Although the combination therapy may improve outcomes in critically ill children with ANE, its effectiveness can vary based on corticosteroid dosing. Currently, MP doses of 20 mg/kg/day and 30 mg/kg/day are the two most commonly used regimens in clinical practice, yet comparative studies evaluating their efficacy and safety remain limited.
To address this, a team of researchers led by Dr. Suyun Qian from the Department of Pediatric Intensive Care Unit, Capital Medical University, China, conducted a retrospective study comparing the efficacy and safety of two different high doses of MP in combination with tocilizumab in children with ANE. The study was published in the journal of
Pediatric Investigation on January 27, 2026.
“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,” says Dr. Qian.
The study included 23 patients with ANE, who were treated with tocilizumab in combination with high-dose MP given either at 20 mg/(kg⋅day) or 30 mg/(kg⋅day). The research team assessed clinical outcomes such as death, anti-inflammatory responses, treatment-related adverse events, and incidence of severe neurological problems in both the treatment groups.
Notably, death rate was lower in the 30 mg/(kg⋅day) group compared to the 20 mg/(kg⋅day) group. In addition, both the doses of MP considerably reduced inflammation as noted by reduced levels of inflammatory cytokines and biomarkers in serum and the cerebrospinal fluid. Further, the group treated with the higher dose of MP exhibited significant neuroprotective advantage with lower proportion of severe neurological sequelae at discharge and during the 6 to 12 months of follow-up.
The observed reduction in severe sequelae despite comparable mortality reflects the distinct pathophysiology of ANE. Both dosing regimens failed to prevent early deaths due to early irreversible damages. In contrast, long-term neurological outcomes are closely linked to subacute inflammatory injury, demyelination, and axonal damage, which are potentially modifiable by timely and potent anti-inflammatory intervention. The strong anti-inflammatory action of the higher-dose MP may offer superior neuroprotection during the critical window of immune-mediated injury.
“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,” says Dr. Qian.
While we await the long-term studies with large cohorts, this study represents a very important first step towards optimizing the treatment protocols for ANE