Child - Infection

Research

The management of infants and children treated with aciclovir for suspected viral encephalitis

Rachel Kneen, Srinivasa Jakka, Renuka Mithyantha, Andrew Riordan and Tom Solomon

Objective
To investigate how infants and children with suspected viral encephalitis are currently managed in a UK tertiary children’s hospital.

Methods
Case note review of all infants and children who received intravenous aciclovir for suspected encephalitis over a six month period. Suspected viral encephalitis was defined as a child with fever or history of febrile illness and a reduced level of consciousness, irritability or a change in personality or behaviour or focal neurological signs.

Results
Fifty-one children were identified. Two had proven herpes simplex encephalitis (HSV) and two had clinically diagnosed viral encephalitis with no cause identified. Forty children had cerebrospinal fluid analysis, but basic results were incomplete in 13 cases. Cerebrospinal fluid was sent for the detection of HSV DNA by polymerase chain reaction in 27 cases. The initial dose of aciclovir was incorrect in 38 cases. The median (range) length of intravenous aciclovir treatment was 4 (1- 21) days. Six children were given a full course of aciclovir (10 or more days). For 14 children, there appeared to be no real indication for starting aciclovir. Case note documentation was generally inadequate.

Conclusions
The management of children with suspected viral encephalitis appears haphazard in many cases. Guidelines for the management of children with suspected viral encephalitis are needed.

Arch. Dis. Child. 2009

The management of infants and children treated with aciclovir for suspected viral encephalitis

The spectrum of herpes simplex encephalitis in children

XAVIER DE TIEGE A, FLORE ROZENBERG B, BENEDICTE HERON C
a Department of Paediatric Neurology, ULB-Hopital Erasme, Brussels, Belgium
b Department of Virology, Hopital Cochin Saint Vincent de Paul, Paris, France
c Department of Paediatric Neurology, Hopital Trousseau, Paris, France

Received 16 May 2007 Received in revised form 5 July 2007 Accepted 10 July 2007

Abstract

Clinical and basic science research carried out in recent years into herpes simplex encephalitis (HSE) have shown that the concept of a ‘‘classical’’ picture of HSE in children is now outdated and that our current knowledge of the disease is probably only the tip of an iceberg. Indeed, increasing evidence supports the existence of a wider range of pathophysiological mechanisms, clinical presentations and disease progressions in paediatric HSE. This paper reviews the clinical, biological and radiological data available and redefines the spectrum of HSE in children. Full understanding of the condition should improve the management of suspected cases and decrease the morbidity and the mortality associated with this disease.

Keywords: Herpes simplex virus, Encephalitis, Children, Relapse

European Journal Of Paediatric Neurology 12 ( 2008 ) 72 – 81

Herpes simplex encephalitis relapses in children: Differentiation of two neurologic entities

X. De Tiège, MD*; F. Rozenberg, MD, PhD*; V. Des Portes, MD, PhD; J.B. Lobut, MD; P. Lebon, MD; G. Ponsot, MD; and B. Héron, MD

Abstract — Relapses of herpes simplex encephalitis (HSE) occurring after the completion of antiviral treatment have been reported repeatedly in children. The authors report data on six children who had at least one relapse of HSE. Two different mechanisms may account for these relapses, including viral replication or an immuno-inflammatory process, with different therapeutic attitudes. Relapses with viral replication may reveal host susceptibility to herpes simplex virus infection.

NEUROLOGY 2003;61:241–243

Herpes Simplex: Encephalitis Children and Adolescents

Richard J. Whitley, MD and David W. Kimberlin, MD

Herpes simplex encephalitis (HSE) remains one of the most devastating infections of the central nervous system despite available antiviral therapy. Children and adolescents account for approximately on third of the cases of HSE. Clinical diagnosis is suggested in the encephalopathic, febrile patient with focal neurologic signs. However, these clinical findings are not pathognomonic because numerous other infections in the central nervous system can mimic HSE. Support for the diagnosis from a neurodiagnostic perspective is aided by the demonstration of disease of the temporal lobe by magnetic resonance era, the can and spike and slow-wave activity on electroencephalogram. In the current era, the gold standard for establishing diagnosis is the detection of herpes simplex virus DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Although PCR is an excellent test and far more desirable than brain biopsy, false negatives can occur early after disease onset. Current therapeutic management calls for the administration of acyclovir at 10mg/kg every 8 hours for 21 days. Even with early administration of therapy after the onset of disease, nearly two thirds of survivors will have sufficient neurologic deficits. Recent investigative efforts are assessing the value of PCR detection of viral DNA at the completion of therapy and the value of prolonged anti viral therapy.

Acute viral encephalitis in childhood

BMJ 1995;310:139-140 (21 January)
www.bmj.com/

Childhood encephalopathy: viruses, immune response, and outcome

Michael Clarke a1, Richard W Newton a2 c1, Paul E Klapper a3, H Sutcliffe a4, I Laing a5 and Geoff Wallace a6

a1 Department of Paediatric Neurology, Leeds General Infirmary, UK.
a2 Department of Paediatric Neurology, Royal Manchester Children's Hospital, UK.
a3 Health Protection Agency, Leeds, UK.
a4 Department of Clinical Biochemistry, Central Manchester Healthcare Trust, Manchester Royal Infirmary, UK.
a5 Department of Clinical Chemistry, Central Manchester Healthcare Trust, Manchester Royal Infirmary, UK.
a6 Department of Paediatric Neurology, Mater Private Hospital, South Brisbane, Queensland, Australia.

Abstract

This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood–brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF:serum albumin ratio indicative of impairment of the blood–CSF and blood–brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN-α levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood–brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood–brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN-α was associated with a good prognosis.

Cambridge Journals
(Accepted June 23 2005)

Correspondence:
c1 Department of Paediatric Neurology, Royal Manchester Children's Hospital, Pendlebury, Manchester M27 4HA, UK. E-mail: Richard.Newton@cmmc.nhs.uk

Human herpesviruses -6 and -7 each cause significant neurological morbidity in Britain and Ireland.

KN Ward, NJ Andrews, CM Verity, and EM Ross.
Arch Dis Child 2005;90:619-623