Reviewed and revised 9 September 2016


  • Encephalitis an acute encephalopathy due to an inflammatory cause
  • Underlying causes are numerous and may be infectious or non-infectious, many of which lack effective therapies
  • Herpes simplex encephalitis is the commonest cause in Australasia and acyclovir should be started as soon as the diagnosis is suspected
  • Always consider epidemiological factors that may indicate an unusual cause of encephalitis (e.g. arboviruses and zoonoses), especially in Australia
  • Encephalitis is commonly fatal or results in significant morbidity


  • inflammation of the brain parenchyma
  •  results in diffuse and/or focal neuropsychological dysfunction
  • there may be coexistent involvement of the meninges (meningoencephalitis)
  •  most cases are viral, but inflammation may result from other infectious (e.g. bacterial, fungal, or protozoan) or autoimmune disorders



  • Viral
    • HSV type 1 or 2, rarely zoster
    • enteroviruses
    • influenza
    • childhood viruses: measles and SSPE, mumps, rubella, EBV, CMV
    • HIV (primary encephalitis, or predispose to secondary in AIDS)
    • arboviruses (e.g. Murray Valley encephalitis, Japanese encephalitis, West Nile virus, flaviviruses, tick-borne encephalitis virus)
    • zoonoses (e.g. rabies, bat lyssavirus, Hendra, Nipah virus)
    • JC virus
  • Bacteria
    • Tb, neurosyphilis, Mycoplasma, Listeria, Coxiella
  • Fungal
    • Cryptococcus
  • Protozoans
    • Toxoplasmosis, cerebral malaria, African trypanosomiasis
  • Prions
    • e.g. CJD, kuru


  • Acute disseminated encephalomyelitis (ADEM) – rapid and widespread demyelination; may occur in association with vaccination or post bacterial or viral infections
  • anti-NMDA receptor encephalitis (various other antibodies)
  • Anti-voltage-gated potassium channel-complex (Anti-VGKC) encephalitis
  • paraneoplastic limbic encephalitis
  • non-paraneoplastic limbic encephalitis
    • e.g. anti-Ri, anti-Yo, anti-glutamic acid decarboxylase (GAD), anti-gamma-amino-butyric acid B receptor (GABA-B-R), anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R), anti-glycine receptor (GlyR), anti-dipeptidyl-peptidase-like protein-6 (DPPX), anti- metabotropic glutamate receptor 5 (mGlu-R5)
  • post-viral (e.g. zoster cerebellitis in children)

Unique infectious etiologies to consider in Australia, include:

  • Hendra virus
  • Australian bat lyssavirus
  • Murray Valley encephalitis virus

Causes of encephalitis that are importnat regionally have potential for introduction into Australia include:

  • Japanese encephalitis virus
  • Enterovirus 71
  • Dengue virus
  • Nipah virus


Conditions that mimic encephalitis include:

  • cerebral abscess
  • meningitis (e.g. partially treated bacterial cause)
  • seizure disorders and post-ictal states
  • intoxications and drug-related hyperthermia syndromes (e.g. NMS)
  • thyroid storm
  • heat stroke



  • history of exposure to mosquitoes, ticks or sick animals that transmit malaria, arboviruses or lyssaviruses
  • history of travel to tropical Australia
    • Dengue, JEV, Endemic flaviviruses, melioidosis, leptospirosis
  • history of immunocompromise
    • Toxoplasmosis, cryptococcus, CMV, EBV
  • not vaccinated?
    • Measles, Mumps, Rubella, VZV
  • may be preceded by a viral prodrome with fever, headache, nausea and vomiting, lethargy, myalgias (highly variable)

Abnormal brain function (diffuse or focal):

  • altered mental status (confused, agitated, obtunded, somnolence)
  • motor and sensory deficits
  • altered behaviour
  • personality changes
  • speech disorders
  • movement disorders
  • seizures
  • hemiparesis
  • cranial nerve palsies
  • exaggerated deep tendon reflexes

Associated features:

  • may be co-existent meningism (meningoencephalitis)
  • vesicles may be present or absent in herpes encephalitis


Encephalitis case definition from the international encephalitis consortium:

  • Major Criterion (required):
    • Patients presenting to medical attention with altered mental status defined as:
      • Decreased or altered level of consciousness, Or
      • Lethargy, Or
      • Personality change
    • And:
      • Lasting ≥ 24 hours
  • Minor Criteria:
    • 2 for possible encephalitis; ≥ 3 for probable or confirmed encephalitis:
      • Documented fever ≥ 38° C within the 72 hours before or after presentation
      • Generalised or partial seizures not fully attributable to a pre-existing seizure disorder
      • New onset of focal neurological findings
      • CSF WBC count ≥ 5 / mm3
      • Abnormality of brain parenchyma on neuroimaging suggestive of encephalitis that is either new from prior studies or appears acute in onset
      • Abnormality on electroencephalography that is consistent with encephalitis and not attributable to another cause
    • And:
      • Exclusion of encephalopathy caused by trauma, metabolic disturbance, tumour, alcohol abuse, sepsis and other non-infectious causes.


Choice depends on index of suspicion based on history and examination

Laboratory tests

  • FBC, CRP, UEC, glucose
  • CSF (lumbar puncture)
    • lymphocytic pleocytosis is common
    • viral meningoencehpalitis pattern:
      • WCC elevated, lymphocytes less than 250, elevated protein, normal or moderately low glucose
    • viral culture
    • PCR
      • HSV:  > 96 % sensitivity between days 3-7 of illness; false positives can occur before 3 days and sensitivity falls in the second week
      • Enterovirus
      • Parechovirus in young children
      • VZV
      • CMV
      • Other viruses if suspected: Measles, HIV, influenza, adenovirus, Hendra virus, Nipah virus,     Australian bat lyssavirus, echovirus, parechovirus.
    • Ziehl–Neelsen stain and TB culture
    • cytology
    • cryptococcal antigen or India Ink
    • CSF IgG
      • HSV IgG in CSF can be used for late diagnosis
      • HZV IgG, may in fact be more sensitive than PCR when interpreted in combination with serum IgG levels
      • Flavivirus IgM (i.e dengue)
  • Serology
    • viruses (e.g. arboviruses; flavirus IgM is most useful after 5 days), HIV
    • syphilis
    • toxoplasmosis
  • malaria screen (ICT, thick and thin films)
  • PCR
    • CSF
    • throat/ nasopharyngeal swabs: enterovirus, influenza A and B, adenovirus
    • fecal: Enterovirus, adenovirus, rotavirus (child), parechovirus (small child/ infant)
  • suspected autoimmune cause:
    • anti-NMDAR, LG1, CASPR2, AMPA, GABA-B, Anti-Hu/ Ma2, VGKC, GAD, DPPX, mGluR5 antibodies
    • vasculitis screen
    • paraneoplastic screen and imaging for underlying tumour


  • CT brain
    • second line imaging if MRI is not available
    • before LP in older patients, signs of raised ICP or focal neurology
    • only 1/3 HSV encephalitis patients have abnormal CT heads
    • can exclude differentials such as intracranial haemorrhage
    • cannot definitively rule out raised intracranial pressure
  • MRI brain
    • first line imaging, more sensitive than CT brain
    • lesions are usually bilateral, in the medial temporal and inferior frontal areas, in HSV encephalitis
    • enhancing multifocal white matter changes (demyelination)
    • West Nile: basal ganglia, thalmi, mesial temporal involvement
    • normal MRI does not exclude encephalitis
    • cannot definitively rule out raised intracranial pressure
  • CXR
    • e.g. TB, melioidosis, cryptococcus

Special tests

  • EEG
    • highly sensitive, poorly specific
    • useful if chronic symptoms or psychiatric presentation
    • paroxysmal lateralizing epileptiform discharges may occur before imaging changes in HSV encephalitis (sensitive, not specific)
    • may diagnosis subtle or non-convulsive seizures
  • Brain biopsy
    • last resort; generally not required due to the availability of PCR
    • considered in patients without a diagnosis who remain unwell or are deteriorating, especially if there are focal lesions on imaging or where CNS vasculitis is suspected
    • may identify treatable diagnoses e.g. Tb, neurosarcoidosis



  • attend to ABCs
  • treat seizures

Specific treatment

  • acyclovir 10mg/kg Q8h IV for 14 days, start prior to definitive imaging
  • empiric antibiotics to cover for bacterial meningitis is often required
  • other specific agents where indicated
    • e.g. anti-malarials
    •  e.g. immunosuppressants for autoimmune causes
    • e.g. anti-HIV therapy
    • e.g. anti-toxoplasmosis agents

Supportive care and monitoring


  • may require HSU/ICU
  • consult as required: infectious diseases, microbiology, neuroradiology, neurology


Worse prognosis if:

  • extremes of age (<1y, >55y)
  • comorbidities
  • immunodeficiency
  • virulent organism

References and links


Journal articles

  • Armangue T, Leypoldt F, Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol. 2014 Jun;27(3):361-8. PMID: 24792345.
  • Britton PN, Eastwood K, Paterson B. Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand. Internal medicine journal. 45(5):563-76. 2015. [pubmed]
  • Huppatz C, Gawarikar Y, Levi C, Kelly PM, Williams D, Dalton C, Massey P, Givney R, Durrheim DN. Should there be a standardised approach to the diagnostic workup of suspected adult encephalitis? A case series from Australia. BMC Infect Dis. 2010 Dec 15;10:353. PMC3018438.
  • Irani SR, Vincent A. Autoimmune encephalitis — new awareness, challenging questions. Discov Med. 2011 May;11(60):449-58. PMID: 21616043.
  • Kramer AH. Viral encephalitis in the ICU. Crit Care Clin. 2013 Jul;29(3):621-49. PMID: 23830656.
  • Simon DW, Da Silva YS, Zuccoli G, Clark RS. Acute encephalitis. Crit Care Clin. 2013 Apr;29(2):259-77. PMID: 23537675.
  • Venkatesan A, Tunkel AR, Bloch KC. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clinical infectious diseases. 57(8):1114-28. 2013. [pubmed]

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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