Excerpts From “Management of suspected viral encephalitis in adults – Association of British Neurologists and British Infection Association National Guidelines”

The following post consists of excerpts from Resource (1) below:

 

The chart above is enlarged below for clarity:

 

Introduction

Although encephalitis is a relatively rare, its importance
lies in that fact that for many forms treatment is effective
if started promptly; in contrast, delays in treatment can be
devastating. Encephalitis means inflammation of the brain
parenchyma, and strictly speaking this is a pathological
diagnosis. However, because of the obvious practical
limitations of this, surrogate clinical markers of inflammation are used (Table 1. Definitions).

Classification of encephalitis

The causes of encephalitis can be defined as those due to
direct infection of the central nervous system (CNS), para-,
or post-infectious causes, and non-infectious causes. Infectious causes include numerous viruses, bacteria (especially intracellular bacteria such as Mycoplasma pneumoniae), parasites and fungi (Table 2. Causes of viral encephalitis; Table 3. Non-viral causes of encephalitis and encephalopathy).

Diagnosing encephalitis

Which clinical features should lead to suspicion of
encephalitis? How do they differ from other encephalopathies? And can they be used to
diagnose the underlying cause?

Recommendations

  • The constellation of a current or recent febrile illness
    with altered behaviour, cognition, personality or consciousness, or new seizures, or new focal neurological signs, should raise the possibility of encephalitis, or another CNS infection; and should trigger appropriate investigations (A, II)
  • Metabolic, toxic, autoimmune and non-CNS sources of
    sepsis as causes for encephalopathy should be considered early in patients presenting with encephalopathy (B, III), especially if there are features suggestive of a non-encephalitic process, such as a past history of similar episodes, symmetrical neurological findings, myoclonus, asterixis, lack of fever, acidosis, or unexplained negative base excess (B, III)
  • Clinical features, such as a sub-acute presentation
    (weeks-months), orofacial dyskinesia, choreoathetosis,
    faciobrachial dystonia, intractable seizures or hyponatraemia, may suggest an antibody-mediated encephalitis, although these features are not all exclusive to antibody-mediated disease (B, II)
  • The investigation priority shown in Table 9 is determined by the patient’s clinical presentation (C, III)

Which patients with suspected encephalitis should
have a lumbar puncture? And in whom should this
be preceded by a computed tomography scan?

Recommendations

  • All patients with suspected encephalitis should have an
    LP as soon as possible after hospital admission, unless
    there is a clinical contraindication (Table 10. Contraindications to an immediate LP) (A, II)
  • If there is a clinical contraindication indicating possible raised intracranial pressure due to or causing brain
    shift, a CT scan should be performed as soon as possible (A, II). An immediate LP following this should ideally be considered on a case-by-case basis, unless the
    imaging reveals significant brain shift or tight basal
    cisterns due to or causing raised ICP, or an alternative diagnosis, or the patient’s clinical condition changes (B, III)
  • If a CT is not needed before an LP, imaging (CT or MRI) should be performed as soon as possible afterwards (A, II)
  • In anticoagulated patients, adequate reversal (with
    protamine for those on heparin and vitamin K, prothrombin complex concentrate, or fresh frozen plasma for those on warfarin) is mandatory before LP (A, II). In patients with bleeding disorders, replacement therapy is indicated (B, II). If unclear how to proceed, advice should be sought from a haematologist (B, III)
  • In situations where an LP is not possible at first, the situation should be reviewed every 24 h, and an LP performed when it is safe to do so (B, II)
  • Lumbar punctures should be performed with needles
    that meet the standards set out by the National Patient
    Safety Agency (A, III)

What information should be gathered from the LP

Recommendations

  • CSF investigations should include:
    – Opening pressure (A, II)
    – Total and differential white cell count, red cell count,
    microscopy, culture and sensitivities for bacteria
    (2 2.5 ml) (A, II)
    – If necessary, the white cell count and protein should
    be corrected for a bloody tap
    – Protein and glucose (1e2 ml), which should be compared with a plasma glucose taken just before the
    LP (A, II)
    – A sample should be sent and stored for virological investigations or other future investigation as indicated
    in the next section (2 ml) (A, II)
    – Mycobacterium tuberculosis (6 ml) when clinically indicated (A, II)
  • If an initial LP is non-diagnostic, a second LP should be
    performed 24e48 h later (B, II)

What virological investigations should be
performed ?

Recommendations

  • All patients with suspected encephalitis should have
    a CSF PCR test for HSV (1 and 2), VZV and enteroviruses,
    as this will identify 90% of cases due to known viral
    pathogens (B, II)
  • Further testing should be directed towards specific pathogens as guided by the clinical features, such as occupation, travel history and animal or insect contact (B, III)

What antibody testing should be done on serum and
CSF?

Recommendations

What antibody testing should be done on serum and
CSF?

Recommendations

  • Guidance from a specialist in microbiology, virology or
    infectious diseases should be sought in deciding on
    these investigations (B, III)
  • For patients with suspected encephalitis where PCR of the CSF was not performed acutely, a later CSF and serum sample (taken approximately 10-14 days after illness onset) should be sent for HSV specific IgG antibody testing (B, III)
  • In suspected flavivirus encephalitis CSF should be
    tested for IgM antibody (B, II)
  • Acute and convalescent blood samples should be taken as an adjunct to diagnostic investigation especially when EBV, arboviruses, Lyme disease, brucellosis, rickettsioses, ehrlichiosis or mycoplasma are suspected (B, II)

What PCR/culture should be done on other samples
(e.g. throat swab, stool, vesicle etc)?

Recommendations

  • Investigation should be undertaken through close collaboration between a laboratory specialist in microbiology or virology and the clinical team (B, III)
    In all patients with suspected viral encephalitis throat
    and rectal swabs for enterovirus investigations should
    be considered (B, II); and swabs should also be sent
    from vesicles, if present (B, II)
  • When there is a recent or concomitant respiratory tract
    infection, sputum (bacteria) or bronchial lavage or nose and throat swab/nasopharyngeal wash or aspirate (viruses) should be sent (B, III)
  • When there is suspicion of mumps CSF PCR should
    be performed for this and parotid gland duct or
    buccal swabs should be sent for viral culture or
    PCR (B, III)

Which patients with encephalitis should have a HIV
test?

Recommendation

  • A HIV test should be performed on all patients with encephalitis or with suspected encephalitis irrespective of interpretation of possible risk factors (A, II)

What is the role of magnetic resonance imaging (MRI) and other advanced imaging techniques in adults with suspected viral encephalitis?

Recommendations

  • MRI (including diffusion weighted imaging), is the preferred imaging modality and should be performed as soon as possible on all patients with suspected encephalitis for whom the diagnosis is uncertain; ideally this should be within 24 h of hospital admission, but certainly within 48 h (B, II)
  • If the patient’s condition precludes an MRI, urgent CT
    scanning may exclude structural causes of raised intracranial pressure, or reveal alternative diagnoses (A, II)
  • The role of MR spectroscopy is uncertain; SPECT and
    PET are not indicated in the assessment of suspected
    acute viral encephalitis (B, II)

Which adults with suspected viral encephalitis
should have an electroencephalogram (EEG)?

Recommendations

  • An EEG need not be performed routinely in all patients
    with suspected encephalitis (A, II). However, for patients with mildly altered behaviour and uncertainty whether there is a psychiatric or organic cause, an EEG should be performed to seek encephalopathic changes (B, II)
  • EEG should also be performed if subtle motor, or nonconvulsive seizures are suspected (B, II)

What is the role of brain biopsy in adults with
suspected viral encephalitis?

Recommendations

  • Brain biopsy has no place in the initial assessment of
    suspected acute viral encephalitis. Stereotactic biopsy
    should be considered in patients with suspected encephalitis in whom no diagnosis has been made after
    the first week, especially if there are focal abnormalities on imaging (B, II)
  • If imaging shows nothing focal, an open biopsy, usually from the non-dominant frontal lobe, may be preferable (B, II)
  • The biopsy should be performed by an experienced neurosurgeon and the histology should be examined by an experienced neuropathologist (B, III)

Treatment of viral encephalitis

For which patients should aciclovir treatment be
started empirically?

Recommendations

  • Intravenous aciclovir (10 mg/kg three times daily)
    should be started if the initial CSF and/or imaging findings suggest viral encephalitis, or within 6 h of admission if these results will not be available, or if
    the patient is very unwell or deteriorating (A, II)
  • If the first CSF microscopy or imaging is normal but the
    clinical suspicion of HSV or VZV encephalitis remains,
    aciclovir should still be started within 6 h of admission
    whilst further diagnostic investigations (as outlined) are awaited (A, II)
  • If meningitis is suspected, patients should be treated in
    accordance with the British Infection Society (now British Infection Association) guideline (A, II)
    The dose of aciclovir should be reduced in patients with
    pre-existing renal impairment (A, II)
  • Patients with suspected encephalitis due to infection
    should be notified to the appropriate Consultant in
    Communicable Disease Control (A, III)

Please see pp 362 + 363 for further information on HSV rx.

What should be the specific management of VZV
encephalitis?

Recommendations

  • No specific treatment is needed for VZV cerebellitis (B, II)
  • For VZV encephalitis, whether due to primary infection
    or reactivation, intravenous aciclovir 10-15 mg/kg
    three times daily is recommended, with or without
    a short course of corticosteroids (B, II)
  • If there is a vasculitic component, there is a stronger
    case for using corticosteroids (B, II)

What should be the specific management of
enterovirus meningoencephalitis?

Recommendation

  • No specific treatment is recommended for enterovirus
    encephalitis; in patients with severe disease pleconaril
    (if available) or intravenous immunoglobulin may be
    worth considering (C, III)

What acute facilities should be available and which
patients should be transferred to a specialist unit

Recommendations

  • Patients with falling level of consciousness require urgent assessment by Intensive Care Unit staff for airway protection and ventilatory support, management of raised intracranial pressure, optimisation of cerebral perfusion pressure and correction of electrolyte imbalances (A, III)
  • Patients with suspected acute encephalitis should have
    access to an immediate neurological specialist opinion
    and should be managed in a setting where clinical neurological review can be obtained as soon as possible and definitely within 24 h of referral (B, III)
  • There should be access to neuroimaging (MRI and CT),
    under general anaesthetic if needed, and neurophysiology (EEG), which may mean transfer to a specialist neuroscience unit (B, III)
  • As CSF diagnostic assays are critical to confirming diagnosis, the results of CSF PCR assays should be available within 24-48 h of a lumbar puncture being performed (B, III)
  • When a diagnosis is not rapidly established or a patient
    fails to improve with therapy, transfer to a neurological unit is recommended. The transfer should occur as soon as possible and definitely within 24 h of being requested (B, III)

How does the management of suspected
encephalitis in the returning traveller differ?

Recommendations

  • Patients returning from malaria endemic areas should
    have rapid blood malaria antigen tests and ideally three thick and thin blood films examined for malaria parasites (A, II)
  • Thrombocytopenia, or malaria pigment in
    neutrophils and monocytes may be a clue to malaria,
    even if the films are negative
  • If cerebral malaria seems likely, and there will be a delay in obtaining the malaria film result, anti-malarial treatment should be considered and specialist advice obtained (A, III)
  • The advice of regional and national tropical and infectious disease units should be sought regarding appropriate investigations and treatment for the other possible causes of encephalitis in a returning traveller (Table 2) (A, III)

What differences are there in the management of
suspected encephalitis in the immunocompromised?

Recommendations

  • 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 (A, III)
  • A CT head scan before LP should be considered in patients with known severe immunocompromise (B, III).
  • If a patient’s immune status is not known, there is no
    need to await the result of an HIV test before performing an LP
  • MRI should be performed as soon as possible in all immunocompromised patients with suspected encephalitis (A, II)
  • Diagnostic microbiological investigations for all immunocompromised patients with suspected CNS infections include (B, II):
    – CSF PCR for HSV 1 & 2, VZV and enteroviruses
    – CSF PCR for EBV, and CMV
    – CSF acid fast bacillus staining and culture for
    M. tuberculosis
    – CSF and blood culture for Listeria monocytogenes
    – Indian ink staining and/or cryptococcal antigen
    (CRAG) testing for Cryptococcus neoformans,
    – Antibody testing and if positive CSF PCR for Toxoplasma gondii,
    – Antibody testing of serum and if positive CSF for
    syphilis
    Other investigations to consider, depending on the circumstances, include (C, III):
    – CSF PCR for HHV6 and 7
    – CSF PCR for JC/BK virus
    – CSF examination for Coccidioides sp and Histoplasma sp
  • Patients with HIV should be treated in an HIV centre
    (A, II)
  • Immunocompromised patients with encephalitis caused
    by HSV-1 or 2, should be treated with intravenous aciclovir (10 mg/kg three times daily) for at least 21
    days, and reassessed with a CSF PCR assay; following
    this long term oral treatment should be considered until
    the CD4 cell count is >200 x 10(6)/L (A, II)
  • Acute concomitant VZV infection causing encephalitis
    should be treated with intravenous aciclovir (A, II)
  • CNS CMV infections should be treated with ganciclovir,
    valganciclovir, forcarnet or cidofovir (A, II)

What differences are there in the presentation and
management of encephalitis associated with antibodies

Recommendations

  • The diagnosis of antibody-mediated encephalitis should
    be considered in all patients with suspected encephalitis as they have a poor outcome if untreated. Moreover,
    the clinical phenotypes of these recently described disorders are still expanding (B, II)
  • Clinical features, such as a sub-acute presentation, orofacial dyskinesia, choreoathetosis, faciobrachial dystonia, intractable seizures or hyponatraemia, may
    suggest an antibody-mediated encephalitis, although
    these features are not exclusive to antibody-mediated
    disease (B, II)
  • All patients with proven VGKC complex or NMDA receptor antibody-associated encephalitis should have
    screening for neoplasm (B, II)
  • Early immune suppression and tumour removal results
    in improved outcomes (B, II)

Evidence
In patients with an acute or more commonly sub-acute
onset of encephalitis, immune-mediated encephalitis
should be considered as the treatment is very different
and early intervention may significantly improve
outcome.138e140

Resources:

(1) Management of suspected viral encephalitis in adults – Association of British Neurologists and British Infection Association National Guidelines [PubMed Abstract] [Full Text HTML] [Full Text PDF]. J Infect. 2012 Apr;64(4):347-73. doi: 10.1016/j.jinf.2011.11.014. Epub 2011 Nov 18.

The above article has been cited by 50 articles in PubMed Central.

(2) SUMMARY DOCUMENT: Management of Suspected Viral Encephalitis in Adults – Association of British Neurologists and British Infection Association National Guidelines [Link is to the Word download – this file can also be opened with OpenOffice which is free].

 

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