Role of Tocilizumab in Severe CNS Inflammatory Presentations in Children

OBJECTIVES: Anti-interleukin 6 receptor (anti-IL6R) therapies have been proven to reduce relapse rates in patients with neuromyelitis optica spectrum disorder and are under investigation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). One anti-IL6R therapy, tocilizumab (TCZ), has been reported as a treatment option in cases of life-threatening MOGAD attacks. The aim of this study was to further evaluate the safety and effectiveness of IV-TCZ for acute and severe CNS inflammatory events in children. METHODS: This retrospective study reviewed medical records of children younger than 18 years treated with IV-TCZ for acute-severe CNS inflammation at the Children's Hospital of Philadelphia between 2022 and 2025, excluding those with new-onset refractory status epilepticus without evidence of CNS inflammation. Clinical features, imaging, serum and CSF profiles, treatments, and outcomes were assessed, with primary evaluation of TCZ response within 72 hours postadministration. RESULTS: Eleven patients were included, of whom 8 demonstrated clinical improvement within 72 hours of IV-TCZ administration. Outcomes included rapid intracranial pressure reduction, recovery in relapsing optic neuritis and myelitis, and improvement in RANBP2-related acute necrotizing encephalopathy. No acute adverse effects were observed. One patient died despite immunotherapy. CSF cytokine panels showed elevated IL-6 in 5 patients, with normal serum IL-6 concentrations. Three of the 5 showed a response to TCZ. DISCUSSION: TCZ may offer potential benefit in select neuroinflammatory conditions, although clinical trials are needed to confirm its efficacy and guide use in such scenarios. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that TCZ improves clinical outcomes in children with acute-severe CNS inflammatory events.