Treatment of severe acute necrotizing encephalopathy of childhood with interleukin-6 receptor blockade in the first 24 h as add-on immunotherapy shows favorable long-term outcome at 2 years

Background: Acute necrotizing encephalopathy (ANE) of childhood is a rare and devastating infection-associated acute encephalopathy. While there are no consensus treatments for ANE, recent case reports suggest a beneficial role for the use of toci-lizumab, a recombinant humanized monoclonal antibody against the interleukin-6 (IL-6) receptor. The correlation of the timing of add-on tocilizumab in relation to long-term outcome has not been reported. Methods: We report on the timing of administration of tocilizumab in two patients classified as high-risk using the ANE severity score (ANE-SS) with respect to the long-term outcome at 2 years. Results: Case 1 was a 19-month-old previously well boy who presented to a tertiary children's hospital with seizures, evolving status dystonicus and shock. Case 2 was a three-year-old boy who presented to a peripheral hospital with fever, sepsis and encephalopathy. The patients were transferred to the tertiary intensive care unit and MRI confirmed ANE with extensive brainstem involvement. Case 1 received intravenous immunoglobulin (IVIg), methylprednisolone and tocilizumab at 21, 39 and 53 h respec-tively. His modified Rankin scale (mRS) at discharge and two years was unchanged at 5. The functional independence measure -for children (WeeFIM) at two years was very low (19/126). Case 2 received dexamethasone at 1 h, methylprednisolone at 21 h and IVIg and tocilizumab at 22 h. The mRS at discharge and two years was 4 and 3 respectively. The WeeFIM score at two years showed substantial improvement (96/126). Conclusion: The very early use of interleukin-6 blockade as 'add-on' immunotherapy in the first 24 h demonstrates potential for improving the long-term outcome in patients classified as high-risk using the ANE-SS. & COPY; 2023 Published by Elsevier B.V. on behalf of The Japanese Society of Child Neurology. All rights reserved.