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.
Acute necrotizing encephalopathy of childhood
Encephalitis
Immunotherapy
Interleukin 6
Long-term outcome
Neurorehabilitation
Tocilizumab
Journal
Brain & development
ISSN: 1872-7131
Titre abrégé: Brain Dev
Pays: Netherlands
ID NLM: 7909235
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
12
10
2022
revised:
28
01
2023
accepted:
06
03
2023
medline:
15
6
2023
pubmed:
27
3
2023
entrez:
26
3
2023
Statut:
ppublish
Résumé
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 tocilizumab, 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. 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. 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 respectively. 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). 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.
Sections du résumé
BACKGROUND
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 tocilizumab, 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
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
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 respectively. 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
CONCLUSIONS
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.
Identifiants
pubmed: 36967317
pii: S0387-7604(23)00045-1
doi: 10.1016/j.braindev.2023.03.002
pii:
doi:
Substances chimiques
Interleukin-6
0
Immunoglobulins, Intravenous
0
Methylprednisolone
X4W7ZR7023
Receptors, Interleukin-6
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
401-407Informations de copyright
Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr Michelle Farrar is the recipient of a National Health and Medical Research Council of Australia Investigator grant (APP1194940), but we have no conflicts of interest to disclose.]