Elsevier

Brain and Development

Volume 31, Issue 3, March 2009, Pages 221-227
Brain and Development

Original article
Outcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin

https://doi.org/10.1016/j.braindev.2008.03.005Get rights and content

Abstract

Objective. To examine the relation between outcome and treatment with steroids and gammaglobulin in children with acute necrotizing encephalopathy. Methods. We retrospectively evaluated the clinical course and outcome of 34 children with acute necrotizing encephalopathy. They were divided into two groups; 17 patients with brainstem lesion and 17 patients without brainstem lesion. Early steroid use was defined as when steroids were administered within 24 h after the onset. The outcome was judged as good when a patient had no or mild cognitive impairment and poor when a patient had more severe sequelae, or died. Results. Among patients without brainstem lesions, the outcome was good in 7 of 12 with early steroid, whereas it was poor in all 5 patients without early steroid. There was no significant difference in sex, age, and laboratory data between patients with and without early steroid. The outcome was not correlated with gammaglobulin treatment. As to patients without brainstem lesions, the outcome was not correlated with early steroid or gammaglobulin treatment. Conclusions. Steroid within 24 h after the onset was related to better outcome of children with acute necrotizing encephalopathy without brainstem lesions. Early steroid treatment will be an important option of the treatment for acute necrotizing encephalopathy.

Introduction

Acute necrotizing encephalopathy (ANE) is a well-defined type of acute encephalopathy described by Mizuguchi et al. [1], [2], [3]. The most prominent feature of ANE is the presence of multiple, symmetric brain lesions in the bilateral thalami and other specific brain regions including periventricular white matter, internal capsule, putamen, upper brain stem tegmentum, and cerebellar medulla, demonstrated by CT or MRI. The onset of ANE is triggered by acute febrile diseases, mostly viral, among which influenza is the most common [2], [4]. ANE is often observed among infants and children, but occasional adult cases have also been reported [1], [5], [6]. Although ANE is common in Japan and Taiwan [2], several reports on ANE have been made from some European and American countries [7], [8], [9].

ANE is often associated with severe neurological symptoms. Onset of ANE occurs during the early febrile period of viral infection and runs a fulminant course with rapid development of coma. The neurological outcome of ANE has been reported to be very poor. According to Mizuguchi, among 51 children with ANE, 14 children died, and 20 survived with moderate or severe neurological deficit [2]. Only 17 of them survived with no or mild neurological sequelae [2].

Several authors have suggested that hypercytokinemia is closely related to the development of ANE. Patients with ANE often have signs of systemic inflammatory response syndrome such as shock, multiple organ failure, and disseminated intravascular coagulation. An association of hemophagocytic syndrome has been reported [10]. These facts indicate that macrophage activation and hypercytokinemia will be participated in the pathogenesis of ANE.

There have been no reports on the treatment against ANE. We postulated that anti-inflammatory treatment can be effective for ANE, if the development of ANE is attributable to systemic inflammatory response. We conducted a retrospective study in order to examine the efficacy of anti-inflammatory treatment including steroids and gammaglobulin.

Section snippets

Patients and method

We retrospectively evaluated the clinical course and outcome of 38 children with ANE recruited from 17 hospitals. We included all patients with ANE who were serially experienced in each hospital. The diagnosis of ANE was made on the basis of neuroradiological findings according to the criteria proposed by Mizuguchi et al. [2], [3]. In this study, we included patients with acute encephalopathy who had multiple focal lesions which were symmetrically distributed in the bilateral thalami and other

Patient characteristics

Patient characteristics in each group were shown in Table 1. The age, sex, a history of febrile seizure or developmental delay was not significantly different between those with and without brainstem lesions. The use of acetaminophene or mephenamate was not different between the two groups. No laboratory data showed a statistically significant difference between the two groups.

Patients without brainstem lesions

In this group, outcome was good in 7 patients and poor in 10. Among 7 patients with good outcome, 6 patients had no

Discussion

This is the first study that revealed the efficacy of early steroid against ANE. The outcome of patients treated with early steroid was better than those without early steroid, if the patients did not have brainstem lesions. The results of our study highlighted the importance of early treatment for children with ANE. The early diagnosis of ANE will not be difficult in most patients, because CT or MRI demonstrates characteristic thalamic lesions from the early stage of the illness. In fact,

Acknowledgements

This study was supported by the Grant from the Ministry of Education, Culture, Sports, Science and Technology (17209037).

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