Guidelines for the management of encephalitis in children
Version of Record online: 28 NOV 2012
© The Author. Developmental Medicine & Child Neurology © 2012 Mac Keith Press
Developmental Medicine & Child Neurology
Volume 55, Issue 2, pages 107–110, February 2013
How to Cite
KIRKHAM, F. J. (2013), Guidelines for the management of encephalitis in children. Developmental Medicine & Child Neurology, 55: 107–110. doi: 10.1111/j.1469-8749.2012.04410.x
- Issue online: 16 JAN 2013
- Version of Record online: 28 NOV 2012
The National Encephalitis Guidelines Development and Stakeholder Groups have recently published guidelines for the management of suspected viral encephalitis in children.1 The guideline review and grade the available evidence with an algorithm (Fig. 1), emphasizing the emergency clinical evaluation at initial presentation in patients without underlying immunosuppression. As the evidence for the benefit of early treatment with aciclovir is unequivocal, encephalopathy secondary to herpes simplex encephalitis (which involves direct brain invasion) is highlighted. There is a lot of information about diagnosis and differential diagnosis in the algorithm, as well as in the tables. This makes it easy to check crucial facts quickly for the benefit of patients who may have herpes simplex encephalitis, e.g. criteria making viral encephalitis more or less likely than tuberculous meningitis once cerebrospinal fluid has been obtained. The algorithm also spells out the recommended dose and duration of treatment for aciclovir in relation to host factors, e.g. immunosuppression and renal failure, and the requirement to repeat cerebrospinal fluid polymerase chain reaction and continue to treat if positive (Fig. 1). Contraindications to lumbar puncture before neuroimaging are included but the authors emphasize that it is essential to undertake this procedure as early as possible in order to establish or exclude a diagnosis of herpes simplex encephalitis, or related herpes encephalitides responsive to aciclovir (such as that due to herpes zoster), so that an optimal treatment strategy can be mapped out.
The guideline arose from a problem previously identified by this group during an audit of the use of aciclovir.2 Of 51 children identified as having received aciclovir over a 6-month period, only 2 (4%) had proven herpes simplex encephalitis and there was no rational basis for treatment in 14. As a result of the emphasis placed on treatable causes in training schedules, aciclovir is commonly the first-line strategy for acute neurological presentations, such as seizures, coma, and focal signs. It is used even in children with underlying conditions, such as renal or cardiac disease, where alternative causes of encephalopathy such as posterior reversible encephalopathy syndrome (Fig. 2[c2,3]) or venous sinus thrombosis (Fig. 2[a2; d2,3]) are more likely but may not be appropriately managed unless a paediatric neurologist or intensivist is consulted. The triage and appropriate management of children presenting with acutely reduced level of consciousness, seizures, or behavioural problems remains a complex and controversial issue. The new guideline emphasizes the importance of neuroimaging in establishing a diagnosis and points out that very rapid computed tomography (CT) is now routine for hospitals with an adult stroke unit. However, CT may miss the diagnosis of herpes simplex encephalitis early on, while magnetic resonance imaging (MRI) is much more specific and sensitive for other conditions as well. Emergency transfer to a regional centre with facilities for urgent out-of-hours MRI under anaesthesia is often essential, especially when diagnosis of other conditions requiring specific treatments may reduce morbidity and mortality, such as aspirin for post-varicella vasculopathy and stroke3,4 (Fig. 2[b3]. Although there have been no randomized trials of aspirin or of the aciclovir or steroids recommended in the guidelines), thrombolysis for basilar occlusion4 (Fig. 2[f2,3]), or anticoagulation for venous sinus thrombosis (Fig. 2[a2; d2,3]).4,5
The distinction between encephalitis and encephalopathy in association with other infection is much less clear and the mechanisms of brain injury are so poorly understood that it is not currently possible to produce evidence-based guidelines. Host factors, such as abnormal fluid balance with hyponatraemia,6 acute anaemia with hypoxia,7,8 raised intracranial pressure and the position of the cerebellar tonsils (Fig. 2[e1]), and blood pressure fluctuations (Fig. 2[c2,3]), may determine the clinical and neuroradiological presentation of infectious encephalopathies. In addition to demyelination, e.g. acute disseminating encephalomyelitis (Fig. 2[d1]), antibody mediated disorders (Fig. 2[b1]), and more specific MRI phenotypes such as mild encephalopathy with a reversible splenial lesion triggered by infection (Fig. 2[c1]) and acute necrotizing encephalomyelitis (Fig. 2[e1,2])1,6,8,9 there may be imaging abnormalities in children with acute febrile seizures.10 Viral ribonucleic acid is not consistently detected in the cerebrospinal fluid of patients with influenza-associated encephalopathy/encephalitis and cerebrospinal fluid pleocytosis is uncommon,11 although many patients with neurological symptoms were treated with antivirals during the recent H1N1 pandemic. Influenza infection may expose specific metabolic disorders, for example disorders of mitochondrial β–oxidation associated with inactivated carnitine palmitoyltransferease II.12 A wide variety of para- and post-infectious neurological symptoms in the context of common infections such as influenza, Lyme disease,12 and mycoplasma pneumoniae may have a vascular4,13 or autoimmune14 basis requiring adjunctive therapy, as well as by directly infecting the central nervous system. Direct viral invasion (encephalitis) and additional mechanisms for encephalopathy are not mutually exclusive.15
The guidelines give a sensible stepwise approach to exclusion of other infectious diseases and strongly recommend consultation with microbiology and/or infectious diseases units. The approach to clinical diagnosis and further research must include an appropriate neuroimaging protocol and good working relationships with neuroradiologists experienced in encephalopathies as well as immunologists so that treatable causes are identified as quickly as possible. Excluding autoimmune conditions requiring specific treatment, such as anti-NMDA receptor antibody encephalitis, is likely to be more cost-effective than an extensive search for viruses, which are less common16 and for which non-specific supportive management is appropriate currently. As networks between peripheral hospitals and tertiary centres with paediatric neurology and intensive care units develop, rapid central triage and emergency management in the acute phase9,13,16,17 followed by longer-term management and rehabilitation locally, perhaps guided from centres with experienced therapists using virtual techniques via Skype, FaceTime, or mobile phones, is likely to improve outcomes. More high quality population-based data on risk factors and outcomes18 are urgently needed so that randomized controlled trials of treatment can be organized.
The author thanks Oliver Morris and Rhea Bhadresha for assistance with the literature review.
- 4Stroke and Cerebrovascular Disease in Childhood. International Review of Child Neurology Series. London: Mac Keith Press, 2011., , editors.