Review articleGuidelines for the diagnosis and treatment of acute encephalopathy in childhood
Introduction
Acute encephalopathy (AE) denotes syndromes characterized by acute onset of severe and long-lasting disturbance of consciousness, which typically occur in previously healthy children. AE is the most severe complication of common infectious diseases, such as influenza and exanthem subitum, often leading to death or severe neurological disabilities [1].
To date, many syndromes of AE have been described. Among them, Reye syndrome was originally reported in Australia [2], and hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome [3] and hemorrhagic shock and encephalopathy syndrome (HSES) [4] in Europe. During 1993–2006, child neurologists in Japan established and characterized many new syndromes, including acute necrotizing encephalopathy (ANE) [5], acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) [6] and clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) [7], and achieved a general consensus upon the syndromic classification of AE by around 2007 [1]. Based on this classification, a nationwide epidemiologic study of AE was conducted in 2010, and the results were published in 2012 [8]. The time was ripe for the compilation of new guidelines.
We aimed to provide clinicians treating acute neurologic disorders of children, such as seizures and impairment of consciousness, with guidelines that are useful for the acute stage management of AE.
Since AE is rare and many of the syndromes were recently characterized, there is only limited information about the diagnosis and treatment. On the other hand, most children with AE are critically ill, requiring prompt and intensive care; thus, there is a great need for guidelines. Until 2013, the only guidelines available for AE had been consensus guidelines specifically targeting influenza-associated AE, published in 2005 and revised in 2009 [9]. Therefore, our purpose was to publish new, evidence-based guidelines targeting AE associated with any pathogen and classified into any syndrome [10].
In September 2013, the Japanese Society of Child Neurology (JSCN) decided to establish clinical practice guidelines for AE, and formed a working group (WG) of ten members and two advisors. From March 2014 to August 2016, the WG formulated guidelines using the methodologies recommended by the Medical Information Network Distribution System (Minds) with minor modifications. Briefly, clinical questions (CQs) were selected, and the system of literature search was determined. Documents in English were retrieved from the PubMed database and those in Japanese from the Ichushi-web were provided by the Japan Medical Abstracts Society. For each CQ, two WG members systematically reviewed the literature, and evaluated the levels of evidence. One of the two members wrote the drafts of recommendations and comments, and then the other reviewed them. For some CQs, additional specialists outside of the WG were invited to critically review the draft: a specialist of electroencephalography (EEG) for CQ 2–4, and intensivists from the Japanese Society of Intensive Care Medicine for CQs 3–2 and 3–3. At the WG meeting, the levels of recommendations (Table 1) were decided and the guidelines were further edited. In February 2016, the WG solicited public comments on the website from the other JSCN members and also asked the following organizations to review the drafts: Japanese Pediatric Society, Japanese Society for Pediatric Infectious Diseases, Japanese Society of Emergency Pediatrics and Chiisana-inochi (an association of families of children with influenza encephalopathy). After revision of the drafts based on the opinions and comments from members and organizations, the guidelines were published in August 2016 [10]. The guidelines were uploaded on the Minds homepage in February 2017.
The guidelines consist of seven chapters, each of them including two to four CQs. The first half (three chapters) of the guidelines, corresponding to Sections 2.1–2.3 in this article, describes the general aspects of AE such as epidemiology and initial management. The second half (four chapters), corresponding to Sections 2.4–2.7, explains the diagnosis and treatment of individual syndromes. In other words, the first and second half deals with the similarities and differences, respectively, among syndromes [10].
Classification into any of the known syndromes may be difficult in some cases, in particular immediately after onset. In other cases, syndromic diagnosis may not be made at all. To facilitate the use of the guidelines in such cases, we illustrated their structure with a flow chart indicating the relevant CQs according to the patient’s clinical findings [10] (Fig. 1).
Section snippets
(CQ1-1) definition of AE
Recommendations:
- (1)
AE is defined as impairment of consciousness of acute onset, with severity of Japan Coma Scale ≥20 or Glasgow Coma Scale (GCS) <11, and with duration of 24 h or longer [10]. (Grading not applicable)
- 1)
The onset usually occurs during the course of infectious diseases.
- 2)
Brain edema is often visualized by cranial computed tomography (CT) or magnetic resonance imaging (MRI).
- 3)
Distinction is made from other diseases, such as encephalitis and meningitis, and from other causes of decreased
- 1)
Limitations and future direction
These guidelines are not intended to show a stereotype of medical management to which a strict compliance is required. The actual strategy of diagnosis and treatment should be decided according to each patient’s condition, the clinician’s experience and the environment of medical care.
In these guidelines, grades of recommendations are either very weak (grade C1) or absent (no grade) for most of the CQs, since little evidence of high quality was available. Thus, even if the diagnosis and
Acknowledgements
The authors are grateful to the Committee for the Integration of Guidelines and Committee for the Support of Collaborative Researches of the JSCN for promoting our studies and activities on AE. This research was supported by Grant-in-Aid for Policy Research for Intractable Diseases, H30-Nanchi-Ippan-007, from the National Institute of Public Health, Japan, and by Grant-in-aid for Scientific Research, No. 15H04872, from the Japan Society for the Promotion of Science.
Disclosure
Compilation cost was covered by JSCN and subsequently covered by sales of the guidelines. The authors have no financial conflict of interest to disclose.
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