Viral Encephalitis in Adults

Viral Encephalitis in Adults - Guideline for the Diagnosis and Management of

Publication: 11/07/2008

Next review: 01/10/2024

Clinical Guideline

CURRENT

ID: 1294

Approved By: Improving Antimicrobial Prescribing Group

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

Diagnostics
Empirical Treatment
Discontinuing Antiviral Therapy

This guideline should be used for adult patients who are suspected of having viral encephalitis. Viral encephalitis should be considered in those who have unexplained fever in combination with:

New seizures (partial and secondary generalised)
Altered behaviour or consciousness
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.

Herpes simplex virus (HSV) is the commonest cause of focal encephalitis in the UK and over 90% of cases are due to infection with HSV type 1.
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.

Bacterial causes of meningoencephalitis should be included in the differential diagnosis. Management of bacterial meningitis is outlined in the Trust guideline.

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

Diagnostics

For patients with a presumed diagnosis of viral encephalitis the following diagnostic tests should be taken to confirm diagnosis:

All patients	Lumbar puncture (LP) should be performed as soon as possible after hospital admission, unless there is a clinical contraindication1,2, in which case CT imaging of the brain should be performed first
	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: PCR for HSV, VZV and enterovirus
	Sending a sample of CSF for storage for possible future analysis for auto immune encephalopathy is also recommended.
	HIV test
	MRI brain should be performed as soon as possible on all patients with suspected encephalitis ideally within 24 hours of hospital admission.
If diagnosis is uncertain	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.
If diagnosis is uncertain	HSV antibody testing on serum and CSF 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 production. This should be performed 10-14 days after onset of symptoms. These samples should be discussed with the consultant virologist prior to sending.
Immunocompromised patients	Stool or throat swabs for enterovirus PCR should be considered in patients with suspected viral encephalitis (particularly if immunocompromised). Swabs should also be sent from skin 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 bacterial culture and viral PCR. When there is suspicion of mumps encephalitis, CSF should be sent for PCR.

Empirical Treatment

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 and a high clinical suspicion of viral encephalitis remains, a second LP should be considered 24-48hrs later.

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 the patient should still be treated within 6 hours of admission.

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

All confirmed cases of viral encephalitis should be discussed with an infection specialist or neurologist.

Empirical options for viral encephalitis
Duration for HSV encephalitis = 14 - 21 days (depending on clinical progress) Prior to stopping treatment a repeat LP should be performed: If the CSF is negative for HSV by PCR then treatment can be stopped If the CSF is still positive for HSV, Aciclovir should be continued intravenously with weekly CSF PCR until it is negative.
	Recommended (1st line) treatment	Notes
All patients with a high index suspicion of encephalitis (HSV or VZV)	Aciclovir * IV 10mg/kg 8-hourly	In obese patients use IBW. Adjust for patients with renal impairment Patients should not be switched to oral therapy. For patients with VZV encephalitis corticosteroids can be considered, especially if there is a vasculitic component. This should be discussed with infectious diseases or virology.
VZV cerebellitis	Continue Aciclovir (as above)
Enterovirus encephalitis	No specific treatment needed
Pregnant or immunocompromised patients	Discuss with an infection specialist
CNS Cytomegalovirus	Discuss with an infection specialist	Options include: ganciclovir, foscarnet, 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 (GCS 15 or GCS unchanged from usual), normal MRI (performed >72 hours after symptom onset), and a CSF white cell count of less than 5/mm3 , or
HSV PCR in the CSF is negative and an alternative diagnosis has been made.

Immunocompromised patients with encephalitis caused by HSV-1 or 2 should be treated with intravenous 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. This should be discussed with an infection specialist.

Provenance

Record:	1294
Objective:
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.
Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL et al. The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases 2008; 47: 303-27

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

FOOTNOTES

Clinical contradictions 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
- Immunocompromise
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.

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