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Determinants of outcomes following acute child encephalopathy and encephalitis: pivotal effect of early and delayed cooling
  1. G Kawano1,
  2. O Iwata2,
  3. S Iwata2,
  4. K Kawano2,
  5. K Obu1,
  6. I Kuki3,
  7. H Rinka4,
  8. M Shiomi5,
  9. H Yamanouchi6,
  10. T Kakuma7,
  11. S Takashima2,
  12. T Matsuishi2
  13. the Research Network for Acute Encephalopathy in Childhood
  1. 1Department of Paediatrics, St Mary's Hospital, Fukuoka, Japan
  2. 2Centre for Developmental and Cognitive Neuroscience, Department of Paediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan
  3. 3Division of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan
  4. 4Emergency and Critical Care Medical Center, Osaka City General Hospital, Osaka, Japan
  5. 5Division of Pediatrics, Osaka City General Hospital, Osaka, Japan
  6. 6Department of Paediatrics, Dokkyo Medical University, Shimotsugagun, Tochigi, Japan
  7. 7Centre for Bio-Statistics, Kurume University School of Medicine, Fukuoka, Japan
  1. Correspondence to Osuke Iwata, Centre for Developmental and Cognitive Neuroscience, Department of Paediatrics and Child Health, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011 Japan; o.iwata{at}


Background Acute encephalopathy/encephalitis is one of the most important causatives of mortality and neurological deficit during childhood. The aim of this retrospective observational study was to investigate clinical variables and therapeutic options associated with the outcome of children with acute encephalopathy/encephalitis.

Methods Relationships between the clinical information at admission and the neurological outcome evaluated using Pediatric Cerebral Performance Category Scale (PCPC) at 12 months after admission were assessed in 43 patients who were treated at 10 Japanese paediatric intensive care units.

Results Sixteen patients were cared for at normothermia, whereas mild hypothermia was applied to 27 children. In univariate analysis, ages ≤18 months, marked elevation in serum lactate dehydrogenase (LD) and aspartate transaminase, diagnosis of either acute necrotising encephalopathy or haemorrhagic shock and encephalopathy syndrome and longer hypothermic periods were associated with increased risks of death or severe neurological deficit, whereas hypothermia showed pivotal effects: the outcome of children cooled after 12 h of diagnosis was statistically invariant with normothermic children, but was significantly worse compared with children cooled ≤12 h. In multivariate analysis, younger ages and elevated serum LD were associated with adverse outcomes, whereas early initiation of cooling was related to favourable outcomes. For normothermic children, PCPC scores were dependent on the computed tomographic findings suggestive of cerebral oedema, serum LD levels and Glasgow Coma Scale at admission. For hypothermic children, PCPC scores depended on longer delays in cooling initiation.

Conclusion Without therapeutic hypothermia, the outcome of children was determined by variables suggestive of the severity of encephalopathy/encephalitis at admission. Hypothermia may have pivotal impacts on the outcome of children according to the timing of cooling initiation following acute encephalopathy/encephalitis.

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  • Research Network for Acute Encephalopathy in Childhood

  • Scientific committee TM (chair), GK (co-principal investigator), OI (co-principal investigator), TK, MS and HR.

  • Hospital investigators HY (Dokkyo Medical University, Shimotsugagun, Tochigi, four patients), H Akaike (Kawasaki Medical School Hospital, Kurashiki, Okayama, two patients), M Uematsu (Tohoku University School of Medicine, Sendai, Miyagi, five patients), M Shimono (University of Occupational and Environmental Health, Kitakyusyu, Fukuoka, one patient), S Hirabayashi, S Hirano (Nagano Children's Hospital, Azumino, Nagano, two patients), T Aoki (Tsukuba Medical Center, Tsukuba, Ibaragi, three patients), IK, HR, MS (Osaka City General Hospital, Osaka, Osaka, 13 patients), H Hamada (Nikko Memorial Hospital, Muroran, Hokkaido, three patients), A Kikuchi, H Yoshikawa (Miyagi Children's Hospital, Sendai, Miyagi, four patients), GK (St Mary's Hospital, Kurume, Fukuoka, six patients).

  • Funding Japanese Ministry of Health, Labor and Welfare and Japanese Ministry of Education, Culture, Sports, Science & Technology.

  • Competing interest None.

  • Ethics approval This study was conducted with the approval of the Kurume University School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.