Abstract
Background
Outcome in severe acute necrotizing encephalopathy of childhood is poor, with high
mortality (30%) and moderate to severe disability in survivors despite the use of
intravenous corticosteroids or immunoglobulins. Increased blood interleukin 6 level
correlates with poor outcome.
Methods
We report the early use of tocilizumab, a monoclonal antibody against the interleukin
6 receptor, in three patients (aged five, eight, and 10 years) with severe acute necrotizing
encephalopathy.
Results
All three patients experienced a rapid neurological deterioration associated with
febrile viral illnesses and met criteria for severe acute necrotizing encephalopathy
with a high risk for death or severe disability. Intravenous methylprednisolone and
tocilizumab were administered at 18 to 32 hours of encephalopathy in addition to supportive
medical therapy. No side effects were observed with this therapeutic strategy. The
two patients with influenza A(H1N1)pdm09 virus-related acute necrotizing encephalopathy
had a short illness with excellent clinical and radiological recovery. The patient
with influenza B virus-related acute necrotizing encephalopathy and florid hemorrhagic
brain lesions had a slow recovery with eventual mild disability despite focal encephalomalacia
on follow-up neuroimaging.
Conclusions
The early use of interleukin 6 blockade in acute necrotizing encephalopathy is safe
and may have a role in improving outcomes and preventing disability.
Keywords
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Article info
Publication history
Published online: April 25, 2019
Accepted:
April 18,
2019
Received:
February 11,
2019
Footnotes
Ethics review and consent: All three patients were enrolled in the Paediatric Autoimmune Epilepsy, Demyelination and Encephalitis Study (PAEDES, CIRB Ref no 2015/2159), an ongoing observational clinical study of children with immune brain disease. Parents of the three children consented to the off-label use of intravenous tocilizumab for immune encephalopathy/encephalitis.
Conflict of interest and source of funding statement: The authors declare no conflict of interest or financial disclosures concerning the materials or methods used in this study or the findings specified in this article.
Author contributions: All authors were involved in patient assessments and data collection. J.C.K. prepared the first draft; A.M. and J.K. contributed to the sections of the manuscript; T.T. was supervising/lead author and conceptualized the treatment strategy. All authors critically reviewed and approved the final manuscript.
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
