Viral encephalitis in adults - Guideline for the diagnosis and management of

Publication: 11/07/2008  --
Last review: 27/04/2018  
Next review: 27/04/2021  
Clinical Guideline
CURRENT 
ID: 1294 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2018  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the diagnosis and management of viral encephalitis in adults

Summary
Viral encephalitis in adults

Criteria for use of guidelines:

  • Adult patients who are suspected of having encephalitis, i.e. those who have unexplained fever in combination with:
    • New seizures (partial and secondary generalised)
    • Altered behaviour or consciousness
    • New focal neurological signs

Investigations required:

  • Lumbar puncture (LP) for suspected encephalitis should be performed as soon as possible after hospital admission, unless there is a clinical contraindication, in which case CT imaging of the brain should be performed first.
  • PCR analysis of CSF is recommended for the diagnosis of viral encephalitis

Antimicrobial treatment:

  • IV Aciclovir electronic Medicines Compendium information on Aciclovir * 10mg/kg, 8 hourly.
  • Aciclovir electronic Medicines Compendium information on Aciclovir should be used empirically if there is a high index of suspicion for encephalitis. Aciclovir electronic Medicines Compendium information on Aciclovir does not affect the sensitivity of PCR in the short term (2-3 days).
  • To avoid excessive Aciclovir electronic Medicines Compendium information on Aciclovir dosage in obese patients, dose should be calculated on the basis of ideal weight for height.
  • Aciclovir electronic Medicines Compendium information on Aciclovir dosage requires adjustment in patients with renal impairment.

Duration of treatment

  • IV Aciclovir electronic Medicines Compendium information on Aciclovir * in HSV encephalitis is used for 14 - 21 days.
  • Prior to stopping treatment, a repeat LP should be performed. If CSF PCR is still positive for HSV, IV Aciclovir electronic Medicines Compendium information on Aciclovir should continue until weekly LPs are negative by PCR.

Switch to oral agent(s)

  • There is no recommendation on switching to oral Aciclovir electronic Medicines Compendium information on Aciclovir * or oral Valaciclovir *

Referral criteria

  • Patients who are pregnant
  • Patients who are immunocompromised

Back to top

Background

Encephalitis can be caused by:

  1. Infection of the central nervous system by viruses, bacteria (especially intracellular bacteria such as Mycoplasma pneumoniae), parasites and fungi.
  2. Para-infectious or post-infectious processes, such as acute disseminated encephalomyelitis (ADEM) following measles virus.
  3. Non-infectious processes, including antibody-associated encephalitis, which may or may not be paraneoplastic. Examples of this include encephalitis associated with antibodies to the voltage-gated potassium channel complex, or N-Methyl-D-Aspartate Antibody (NMDA) receptors.

Herpes simplex virus (HSV) encephalitis is the commonest cause of focal encephalitis in the UK and over 90% of cases are due to infection with HSV type 1. HSV encephalitis has an annual incidence of approximately 1 in 250,000 to 500,000. The age specific incidence is bimodal, with peaks in the young and the elderly.

Varicella zoster virus (VZV) is also a relatively common cause of viral encephalitis, especially in the immunocompromised, whilst Cytomegalovirus (CMV) encephalitis occurs almost exclusively in this group.

Enteroviruses most often cause aseptic meningitis, but can rarely be an important cause of encephalitis.

Back to top

Clinical Diagnosis

Viral encephalitis typically presents with fever, alongside altered behaviour or consciousness, or new seizures, or new focal neurological signs. Encephalitis should be considered in immunocompromised patients with altered mental status, even if the history is prolonged, the clinical features are subtle or there is no febrile element.

Other causes of encephalopathy should be considered, including metabolic, toxic and autoimmune, especially if there is a lack of fever, symmetrical neurology or a past history of similar episodes.

Back to top

Investigation

Lumbar puncture (LP) for suspected encephalitis should be performed as soon as possible after hospital admission with CT or MRI imaging afterwards, unless there is a clinical contraindication.

Clinical contraindications to LP before imaging include:

  • Moderate-severe impairment of consciousness: reduced or fluctuating GCS <13 or fall >2
  • Focal neurological signs, including:
    • unequal, dilated or poorly responsive pupils, or ‘doll’s eye’ movements
    • abnormal posture or posturing
    • seizures
  • Signs of raised intracranial pressure, including:
    • Papilloedema
    • Relative bradycardia with hypertension
  • Immunocompromised

If there is a clinical contraindication indicating possible raised intracranial pressure due to or causing brain shift, a computed tomography (CT) imaging should be performed prior to LP. If CT imaging shows significant brain shift or tight basal cisterns, LP should be deferred. In situations where a LP is not possible at first, the situation should be reviewed every 24 hours, and a LP performed when it is safe to do so.

Cerebrospinal fluid (CSF) investigations should include:

  • opening pressure
  • total and differential white cell count, red cell count,
  • protein and glucose, which should be compared with a plasma glucose taken just before LP
  • microscopy, culture and sensitivities for bacteria,
  • virological investigations

CSF findings consistent with viral encephalitis include normal or raised protein levels, normal or decreased glucose CSF/serum ratio and raised leucocyte count (often both polymorphonuclear and mononuclear cells being seen). If an initial LP is non-diagnostic, a second should be performed 24-48hrs later.

All patients with suspected encephalitis should have a CSF polymerase chain reaction (PCR) test for HSV (1 and 2), VZV and enteroviruses, as this will identify 90% of cases due to viral pathogens.

HSV antibody testing on serum and CSF is only recommended when the PCR result does not support the clinical and radiological findings, or where CSF PCR was not performed acutely. In such cases, paired serum and CSF should be collected to look for intrathecal antibody. This should be performed 10-14 days after onset of symptoms. These samples should be discussed with the consultant virologist prior to sending.

Stool or throat swabs for enterovirus PCR should be considered in patients with suspected viral encephalitis (particularly if immunocompromised) and swabs should also be sent from vesicles, if present. When there is a history of recent or concomitant respiratory tract infection, sputum, bronchial lavage washings or nose/throat swabs should be sent for bacteria culture and viral PCR. When there is suspicion of mumps encephalitis, CSF should be sent for PCR.

A HIV test should be offered to all patients presenting with suspected encephalitis.

MRI brain should be performed as soon as possible on all patients with suspected encephalitis ideally within 24 hours of hospital admission.

An electroencephalogram (EEG) does not need to be performed routinely in all patients with suspected encephalitis, but may be considered if the diagnosis is uncertain.

Back to top

Treatment

The outcome of patients with HSV encephalitis has been shown to be dramatically improved with Aciclovir electronic Medicines Compendium information on Aciclovir treatment. Delays in starting treatment, particularly beyond 48 hours after hospital admission, are associated with a worse prognosis.

The empiric treatment of adults suspected to have viral encephalitis is:

  • IV Aciclovir electronic Medicines Compendium information on Aciclovir * 10mg/kg, 8 hourly
    • To avoid excessive dosage in obese patients, parenteral Aciclovir electronic Medicines Compendium information on Aciclovir doses should be calculated on the basis of ideal weight for height. The dose of Aciclovir electronic Medicines Compendium information on Aciclovir requires adjustment in the presence of renal impairment.

Treatment should be started if the initial CSF and/or imaging findings suggest encephalitis or within 6 hours of admission if these results will not be available, or if the patient is very unwell or deteriorating.

If the first CSF microscopy is normal but the clinical suspicion of HSV or VZV encephalitis remains, Aciclovir electronic Medicines Compendium information on Aciclovir should still be started within 6 hours of admission.

At present, there is insufficient evidence to recommend use of steroids in patients with HSV encephalitis.

No specific treatment is needed for VZV cerebellitis. For VZV encephalitis, whether due to primary infection or reactivation, intravenous aciclovir 10mg/kg 8 hourly is recommended, with or without a short course of corticosteroids. If there is a vasculitic component, there is a stronger case for using corticosteroids.

No specific treatment is recommended for enterovirus encephalitis. In patients with severe disease pleconaril (if available) or intravenous immunoglobulin may be considered, but would require discussion with an immunologist.

CNS Cytomegalovirus infections should be treated with ganciclovir, foscarnet or cidofovir.

Discontinuing antiviral therapy

Antiviral therapy may be discontinued in an immunocompetent patient if:

  • HSV PCR in the CSF is negative on two occasions 24-48 hours apart, and MRI is not characteristic for HSV Encephalitis, or
  • HSV PCR in the CSF is negative once >72 hours after neurological symptom onset, with unaltered consciousness, normal MRI (performed >72 hours after symptom onset), and a CSF white cell count of less than 5/mm3 (EG), or
  • HSV PCR in the CSF is negative and an alternative diagnosis has been made.

Immunocompromised patients:

Encephalitis should be considered in immunocompromised patients with altered mental status, even if the history is prolonged, the clinical features are subtle, there is no febrile element, or the CSF white cell count is normal. MRI should be performed as soon as possible in all immunocompromised patients with suspected encephalitis.

Immunocompromised patients with encephalitis caused by HSV-1 or 2 should be treated with intravenous Aciclovir electronic Medicines Compendium information on Aciclovir for at least 21 days, and reassessed with a CSF PCR assay. Following this, long term oral treatment may be considered depending on the clinical circumstance, for example, until the CD4 count is >200x106/L in HIV positive patients.

Back to top

Duration of Treatment
  • In patients with proven HSV encephalitis, intravenous Aciclovir electronic Medicines Compendium information on Aciclovir should be continued for 14 - 21 days
  • Prior to stopping treatment, a repeat LP should be performed:
    • If the CSF is negative for HSV by PCR treatment can be stopped
    • If the CSF is still positive for HSV by PCR, Aciclovir electronic Medicines Compendium information on Aciclovir should continue intravenously, with weekly CSF PCR until it is negative

Back to top

Switch to oral agent(s)

There is no recommendation to switch to oral Aciclovir electronic Medicines Compendium information on Aciclovir *

Back to top

Provenance

Record: 1294
Objective:
  • To provide evidence-based recommendations for appropriate investigation of herpes simplex encephalitis
  • To provide evidence-based recommendations for appropriate empirical and directed antimicrobial therapy for herpes simplex encephalitis
  • To recommend appropriate dose, route of administration and duration of antimicrobial agents.
  • To set-out criteria for referral to specialists.
Clinical condition: Viral encephalitis
Target patient group: Adults
Target professional group(s): Primary Care Doctors
Secondary Care Doctors
Adapted from:

Evidence base

This guideline is an adaptation of The Encephalitis Society Professional Guidelines for the Management of Suspected Viral Encephalitis in Adults, which is a synopsis of:
Solomon T., Michael B.D. (joint first), Smith P.E., Sanderson F., Davies N.W.S., Hart I.J., Buckley C., Holland M., Easton A., Kneen R., Beeching N.J. On behalf of the National Encephalitis Guidelines Development Group. Management of suspected viral encephalitis in adults: Association of British Neurologists and British Infection Association National Guideline. Journal of Infection 2012; 64(4):347-73.

Reference has also been made to:

International Herpes Management Forum (2004). Herpes Infections of the Central Nervous System. Herpes 11(supp 2):1470-1537

Whitley, R.J. (2006). Herpes simplex encephalitis: Adolescents and adults. Antiviral research 71:141-148.

Evidence Levels

A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus
D. LTHT consensus

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

Not supplied

Equity and Diversity

The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.