Herpes Simplex Virus Encephalitis in Infants and Children ( 1 month - 16 years )
|Last review: 15/08/2018|
|Next review: 15/08/2021|
Supported by: Improving Antimicrobial Prescribing Group
Approved By: Drug and Therapeutics Committee
|Copyright© Leeds Teaching Hospitals NHS Trust 2018|
This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
Guideline for the Management of Herpes Simplex Virus Encephalitis in Infants and Children (1 month - 16 years)
Herpes Simplex Virus Encephalitis in Infants and Children ( 1 month - 16 years )
This guideline applies to infants and children with confirmed herpes simplex virus encephalitis (HSE).
These symptoms may fluctuate but generally have a deteriorating trend.
NB Children may be managed initially according to Guideline for the initial management of a child with a fever and seizure or suspected acute CNS infection.
N.B Aciclovir should be continued if there is a high index of suspicion that this is HSE even if the CSF PCR is negative.
IV Aciclovir *
*To avoid excessive dose in obese patients parenteral dose should be calculated on the basis of ideal weight for height (as per BNFc).
Duration of therapy
Aciclovir can be stopped if HSV PCR is negative (>72 hours after onset of illness) and low clinical suspicion.
Switch to oral agents
Herpes simplex virus encephalitis (HSE) is an acute focal necrotizing encephalitis with inflammation and swelling of brain tissue. It represents about 10% of all severe viral CNS infections. Thirty one percent of cases occur in patients below 20 years of age and 12% in those between 6 months and 10 years 2, 3. In children (and adults) the mortality in untreated HSE is 70%, 19% in treated HSE but greater than 50% of survivors have neurological sequelae4.
It is important to have a low threshold to consider HSE due to the potential severity of its outcome and because it is treatable.
For this guideline to apply, a confirmed case of HSE is defined as:
1) clinical findings consistent with HSE (see Clinical Diagnosis section)
2) radiological evidence of HSE on CT or MRI scanning the head AND/OR a positive Herpes simplex virus PCR (see Investigations section)
HSE can present with reduced consciousness (lethargy, decreased Glasgow Coma score or coma), abnormal behaviour, focal neurological signs or seizure and a fever and cases are likely to be initially managed according to Guideline for the initial management of a child with a fever and seizure or suspected acute CNS infection.
Recommendation: A child that does not recover from a “febrile seizure” within an hour should be investigated and treated for encephalitis6
Focal signs and symptoms may also be present (one or more of the following)
The symptoms of encephalitis are preceded in 60%5 of cases by prodromal symptoms that may just be fever and malaise often lasting a few days. Fever may develop after the onset of neurological symptoms1.
One third of cases will have skin, eye or mouth manifestations of HSV. Signs and symptoms that may be present are:
Recommendation: If there are no contraindications, lumbar puncture (LP) should be performed in all cases of suspected HSE and cerebrospinal fluid (CSF) sent for microscopy, bacterial culture, protein, glucose (paired with blood), HSV polymerase chain reaction (PCR)
Recommendation: If a LP was initially contraindicated, it can be done later in the course of the illness (and sent for tests above) if the contraindications are resolved.
Recommendation: If the CSF HSV PCR result is negative (early in the course of the illness) and the diagnosis of HSE is considered likely, a LP should be repeated and CSF sent for HSV PCR.
Recommendation: If the CSF HSV PCR result is negative (≤72 hours after onset of symptoms) and the diagnosis of HSE is considered likely, and a repeat LP is contraindicated, a blood sample should be sent for HSV IgM and IgG testing.
Recommendation: If symptoms persist at the end of a treatment course a repeat CSF PCR analysis should be considered prior to therapy being altered (see also, duration section)
Recommendation: If skin vesicles are present, vesicle fluid should be sent for viral PCR.
Recommendation: MRI (including diffusion weighted imaging), should be performed as soon as possible on all patients with suspected encephalitis in whom the diagnosis is uncertain; ideally this should be within 24 hours of hospital admission, but certainly within 48 hours.
Where the patient’s clinical condition precludes an MRI, urgent CT scanning may reveal an alternative diagnosis.
Recommendation: An Electroencephalogram (EEG) should not be performed routinely in all patients with suspected encephalitis; however, in patients with mildly altered behaviour, if it is uncertain whether there is a psychiatric or organic cause an EEG should be performed to establish whether there are encephalopathic changes. EEG should also be performed if subtle motor or subclinical seizures are suspected. An EEG should be performed in children with suspected chronic viral encephalitis for example sub-acute sclerosing panencephalitis (SSPE).
Look for evidence of raised intracranial pressure and manage this.
Recommendation: Aciclovir can be nephrotoxic and it is important to ensure that the patient is well hydrated.
Recommendation: When a diagnosis of HSE is confirmed, consider early insertion of a long line for administration of IV Aciclovir .
|Empirical Antimicrobial Treatment|
Recommendation: Empirical Aciclovir therapy should be reviewed with the results of investigations.
Recommendation: Aciclovir may be discontinued if a negative CSF HSV PCR test is obtained at >72 hours following onset of neurological symptoms in a patient with a low probability of having HSE.
If a child has HSE, referral to the paediatric neurology team for advice regarding investigation, management and treatment is appropriate.
|Directed Antimicrobial Treatment (when microbiology results are known)|
Recommendation: Aciclovir (dosed as below) is the treatment of choice for children with confirmed HSE.
*To avoid excessive dose in obese patients parental dose should be calculated on the basis of ideal weight for height. (as per BNFc)
Recommendation: A full course of Aciclovir therapy should be given to children with confirmed HSE (dose and route as above). [Evidence level B]
|Duration of Treatment|
Recommendation: 21 days of IV Aciclovir is recommended.
|Switch to oral agent(s)|
Recommendation: Oral Aciclovir is not appropriate for treatment of HSE. [Evidence level C]
Herpes simplex virus encephalitis
|Target patient group:||Children with Herpes simplex virus encephalitis|
|Target professional group(s):||Pharmacists
Secondary Care Doctors
Secondary Care Nurses
- De Tiege, X., et al., Herpes simplex encephalitis: diagnostic problems and late relapse. Dev Med Child Neurol, 2006. 48(1): p. 60-3.
- Whitley RJ, Alford CA (1982) Herpesvirus infections in childhood: diagnostic dilemmas and therapy. Pediatr Infect Dis 1: 81-4
- Whitley RJ, Kimberlin DW (2005) Herpes simplex encephalitis: children and adolescents. Seminars Pediatr Infect Dis 16:17-23
- Davies EG, de Souza C (1993). How to investigate and manage the child with suspected acute encephalitis. Current Paediatrics 3:106-113
- Diseases of the nervous system in Childhood 3rd edition. Aicardi.
- Allen et al (2007) Recovery of consciousness following epileptic seizures in children. Arch Dis Child. Jan; 92(1):39-42.
- Diagnosis of Herpesvirus Infections of the CNS • Herpes 11 Supp 2 2004
- R. Kneen , B.D. Michael, E. Menson, B. Mehta, A. Easton, C. Hemingway, P.E. Klapper, A. Vincent, M. Lim, E. Carrol, T. Solomon. On behalf of the National Encephalitis Guidelines Development and Stakeholder Groups (2012). Management of suspected viral encephalitis in children e Association of British Neurologists and British Paediatric Allergy, Immunology and Infection Group National Guidelines Journal of Infection 64, 449-477
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)
Drug and Therapeutics Committee
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