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Guideline Summary
Guideline Title
Viral meningoencephalitis: a review of diagnostic methods and guidelines for management.
Bibliographic Source(s)
Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O, Kennedy PG. Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol. 2010 Aug;17(8):999-e57. [99 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O, Kennedy PG. Viral encephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol 2005 May;12(5):331-43.

Scope

Disease/Condition(s)

Viral meningoencephalitis (viral encephalitis)

Guideline Category
Diagnosis
Evaluation
Management
Treatment
Clinical Specialty
Critical Care
Emergency Medicine
Family Practice
Infectious Diseases
Internal Medicine
Neurology
Pediatrics
Intended Users
Advanced Practice Nurses
Nurses
Physician Assistants
Physicians
Guideline Objective(s)

To address the optimal clinical approach to central nervous system infections caused by viruses

Target Population

Patients presenting with or suspected of having viral encephalitis

Interventions and Practices Considered

Diagnosis/Evaluation

  1. Medical history
  2. Physical examination (general and neurological)
  3. Diagnostic investigations:
    • General work-up (peripheral blood count and cellular morphology, erythrocyte sedimentation rate, blood cultures, chest x-ray)
    • Electroencephalography (EEG)
    • Analysis of cerebrospinal fluid (CSF) for protein, glucose, and cellular analysis
    • Serology
    • Polymerase chain reaction (PCR) amplification
    • Neuroimaging (preferably by magnetic resonance imaging [MRI])
    • Viral culture (no recommendation since rarely useful)
    • Brain biopsy for difficult cases

Management/Treatment

  1. Hospitalization with an access to intensive care units and supportive therapy
  2. Acyclovir
  3. Ganciclovir
  4. Foscarnet
  5. Pleconaril
  6. Corticosteroids as an adjunct treatment
  7. Surgical decompression
Major Outcomes Considered
  • Usefulness, sensitivity, and specificity of diagnostic tests
  • Effectiveness of treatment

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

MEDLINE (National Library of Medicine) was searched for relevant literature from 1966 to September 2009. The search included reports of research in humans only and in English. The search terms selected were as follows: 'viral encephalitis', 'encephalitis', 'viral meningitis', 'meningoencephalitis', and 'encephalomyelitis'. Then the search was limited using the terms 'diagnosis', 'MR', 'PET', 'SPECT', 'EEG', 'cerebrospinal fluid', 'pathology', 'treatment/' and 'antiviral therapy'. Review articles and book chapters were also included if they were considered to provide comprehensive reviews of the topic. The final choice of literature and the references included was based on the judgment of their relevance to the subject.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Evidence Classification Scheme for a Diagnostic Measure

Class I: A prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where the test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy.

Class II: A prospective study of a narrow spectrum of persons with the suspected condition, or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy.

Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation.

Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls).

Good practice point (GPP) Where there was lack of evidence but consensus was clear the Task Force members have stated their opinion as good practice points.

Evidence Classification Scheme for a Therapeutic Intervention

Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:

  1. Randomization concealment
  2. Primary outcome(s) is/are clearly defined
  3. Exclusion/inclusion criteria are clearly defined
  4. Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
  5. Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences

Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e.

Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment.

Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.

Methods Used to Analyze the Evidence
Systematic Review
Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

Recommendations were reached by consensus of all Task Force participants and were also based on their awareness and clinical experience. Where there was lack of evidence but consensus was clear the Task Force members have stated their opinion as good practice points (GPP).

Rating Scheme for the Strength of the Recommendations

Rating of Recommendations for a Diagnostic Measure

Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent, convincing class II studies.

Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.

Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.

Rating of Recommendations for a Therapeutic Intervention

Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.

Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.

Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.

Good Practice Point (GPP) Where there was lack of evidence but consensus was clear the Task Force members have stated their opinion as good practice points.

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
Peer Review
Description of Method of Guideline Validation

The guidelines were validated according to the European Federation of Neurological Societies (EFNS) criteria (see "Availability of Companion Documents").

Recommendations

Major Recommendations

The levels of evidence (Class I-IV, Good Practice Point [GPP]) supporting the recommendations and ratings of recommendations (A-C) are defined at the end of the "Major Recommendations" field.

Recommendations for Diagnostic Tests

Viral encephalitis is still an evolving discipline in medicine. The emergence of new, and re-emergence of old pathogens and the constant search for specific therapeutic measures, unavailable in most viral encephalitis cases, suggest that the following years will bring new developments in diagnosis and therapy. At present, adherence to a strict protocol of diagnostic investigations is recommended and includes the following:

Study Findings Level of Recommendation Class of Evidence
LP Cells: 5 to 500 white blood cells, mainly lymphocytes; may be xanthochromic with red blood cells.
Glucose: normal (rarely reduced).
Protein: >50 mg/dL.
A II
Serology CSF and serum B II
PCR Major aid in diagnosis (CSF).
May be false negative in the first 2 days of disease.
A I
EEG Early and sensitive.
Non-specific. May identify focal abnormalities.
C III
Imaging MRI is usually more sensitive than CT, demonstrating high signal intensity lesion on T2-weighted and FLAIR images. B II
Viral culture Only rarely useful.    
Brain biopsy Highly sensitive.
Not used routinely.
C III and GPP

Abbreviations: CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalogram; FLAIR, fluid-attenuation inversion recovery; LP, lumbar puncture; MRI, magnetic resonance imaging; PCR, polymerase chain reaction

Recommendations for Therapeutic Interventions

The following are the specific and symptomatic therapeutic measures available for viral encephalitis:

Interventions Class of Evidence Level of Recommendation
Acyclovir for HSE II A
Acyclovir for suspected viral encephalitis IV (-)
Acyclovir for VZV encephalitis IV (-)
Ganciclovir and/foscarnet for CMV encephalitis IV (-)
Acyclovir or ganciclovir for B virus encephalitis IV (-)
Pleconaril for enterovirus encephalitis Not available (-)
Corticosteroids for viral encephalitis IV  
Surgical decompression IV  

Abbreviations: CMV, cytomegalovirus; HSE, herpes simplex encephalitis; VZV, varicella-zoster virus

Definitions:

Evidence Classification Scheme for a Diagnostic Measure

Class I: A prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where the test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy.

Class II: A prospective study of a narrow spectrum of persons with the suspected condition, or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy.

Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation.

Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls).

Good practice point (GPP) Where there was lack of evidence but consensus was clear the Task Force members have stated their opinion as good practice points.

Evidence Classification Scheme for a Therapeutic Intervention

Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:

  1. Randomization concealment
  2. Primary outcome(s) is/are clearly defined
  3. Exclusion/inclusion criteria are clearly defined
  4. Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
  5. Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences

Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e.

Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment.

Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.

Rating of Recommendations for a Diagnostic Measure

Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent, convincing class II studies.

Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.

Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.

Rating of Recommendations for a Therapeutic Intervention

Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.

Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.

Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for selected recommendations (see "Major Recommendations").

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Correct immediate diagnosis and introduction of symptomatic and specific therapy has a dramatic influence upon survival and reduces the extent of permanent brain injury.

Potential Harms

Diagnostic Tests

Polymerase chain reaction (PCR) may render false-negative results in the first 2 days of disease.

Adverse Effects of Medication

  • As more than 80% of acyclovir in circulation is excreted unchanged in urine, renal impairment can precipitate acyclovir toxicity and high dose acyclovir in overweight or obese patients may precipitate renal failure. Rarely, acyclovir can induce a toxic encephalopathy, and therefore, it is important to establish an early diagnosis of herpes simplex encephalitis (HSE) to avoid diagnostic confusion.
  • Foscarnet should be used only in patients with clinically suspected HSE who continue to deteriorate despite acyclovir therapy with a reactive cerebrospinal fluid (CSF) in whom alternative possibilities have been excluded. Foscarnet can also precipitate a dose-related, reversible renal impairment.

Qualifying Statements

Qualifying Statements

This guideline provides the view of an expert task force appointed by the Scientific Committee of the European Federation of Neurological Societies (EFNS). It represents a peer-reviewed statement of minimum desirable standards for the guidance of practice based on the best available evidence. It is not intended to have legally binding implications in individual cases.

Implementation of the Guideline

Description of Implementation Strategy

The European Federation of Neurological Societies has a mailing list and all guideline papers go to national societies, national ministries of health, World Health Organisation, European Union, and a number of other destinations. Corporate support is recruited to buy large numbers of reprints of the guideline papers and permission is given to sponsoring companies to distribute the guideline papers from their commercial channels, provided there is no advertising attached.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
IOM Domain
Effectiveness

Identifying Information and Availability

Bibliographic Source(s)
Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O, Kennedy PG. Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol. 2010 Aug;17(8):999-e57. [99 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2005 May (revised 2010 Aug)
Guideline Developer(s)
European Federation of Neurological Societies - Medical Specialty Society
Source(s) of Funding

European Federation of Neurological Societies

Guideline Committee

European Federation of Neurological Societies Task Force

Composition of Group That Authored the Guideline

Task Force Members: I. Steiner, Department of Neurology, Rabin Medical Center, Beilinson Campus, Petach Tiqva; Laboratory of Neurovirology, Department of Virology, Hadassah University Hospital, Jerusalem, Israel; H. Budka, Institute of Neurology, Medical University of Vienna, Wien, Austria; A. Chaudhuri, Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK; M. Koskiniemi, Department of Neurology, Essex Centre for Neurological Sciences, Queen's Hospital, Romford, UK; K. Sainio, Department of Clinical Neurophysiology, University of Helsinki; O. Salonen, Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland; P. G. E. Kennedy, Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland, UK

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O, Kennedy PG. Viral encephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol 2005 May;12(5):331-43.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the European Federation of Neurological Societies (EFNS) Web site External Web Site Policy.

Print copies: Available from Dr I. Steiner, Department of Neurology, Hadassah University Hospital, PO Box 12 000, Jerusalem, 91 120, Israel; Phone: 972 2 6776952; Fax: 972 2 6437782; E-mail: isteiner@md2.huji.ac.il

Availability of Companion Documents

The following is available:

  • Brainin M, Barnes M, Baron JC, Gilhus NE, Hughes R, Selmaj K, Waldemar G; Guideline Standards Subcommittee of the EFNS Scientific Committee. Guidance for the preparation of neurological management guidelines by EFNS scientific task forces – revised recommendations 2004. Eur J Neurol. 2004 Sep;11(9):577-81. Electronic copies: Available in Portable Document Format (PDF) from the European Federation of Neurological Societies (EFNS) Web site External Web Site Policy.
Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI on December 4, 2006. The information was verified by the guideline developer on January 15, 2007. This NGC summary was updated by ECRI Institute on February 3, 2011. The updated information was verified by the guideline developer on April 21, 2011.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the Blackwell-Synergy copyright restrictions.

Disclaimer

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