Original articleOutcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin
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.
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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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