The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good Practice Point [GPP]) 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, suggests 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:
| Study |
Finding |
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)
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:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- 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.
Good Practice Points (GPPs) Where there was lack of evidence but consensus was clear the Task Force members have stated their opinion as good practice points
