HSV Encephalitis

Reviewed and revised 2 February 2014


  • severe viral infection of the central nervous system, caused by a herpes simplex virus and usually localised to the temporal and frontal lobe
  • most commonly identified cause of infectious encephalitis
  • 5-10% of encephalitis cases worldwide
  • affects all ages, but is most common, and most severe, in children (33% <20y) and the elderly (50% >50y)
  • the classic triad of fever, headache and altered


  • HSV-1 encephalitis is more common in adults
  • HSV-2 infection is more common in neonates


Classic presentation

  •  flu-like illness with malaise, N&V (50%), headache (80%) and fever (90%)
  • followed by seizures (may be focal; 70%), cognitive impairment (25%), behavioural changes (70%), and/ or focal neurological deficits (33%)

Variable presentation patterns are common, such as

  • absent viral prodrome
  • altered mental state may only be subtle
  • focal neurological deficits (may resemble stroke or other neurological disorders)

Prodromal symptoms and focal deficits are less common in the immunocompromised



  • MRI (or CTB if MRI not available)
  • LP (unless contra-indicated; e.g. mass effect on imaging or coagulopathy)
  • other tests guided by condition and need to exclude other diagnoses

MRI is the diagnostic modality of choice

  • abnormal in 90%; but changes are not specific for HSV (e.g. limbic encephalitis, MCA ischaemia, tumours, effects of seizures)
  • hyperintense T2 signal in the medial temporal lobes, inferior frontal lobes and insula
  • Basal ganglia are usually spared
  • T1 signal is hypointense, consistent with edema
  • Mild patchy gyral or cisternal contrast enhancement may occur
  • Diffusion weighted imaging and FLAIR may be more sensitive for early HSV encephalitis than T2 weighted images

Lumbar puncture/ CSF

  • raised lymphocyte count (10–500×106/L, average 100×106/L)
  • +/- RBCs +/- xanthochromia (encephalitis may be haemorrhagic)
  • mildly raised protein levels
  • normal or mildly decreased glucose
    — sensitivity 96–98%, specificity 95–99%
    — may be undetectable early; consider repeat after 3-7 days
    — remains positive for 5-7 days after antiviral therapy
    — brain biopsy now no longer needed


  • high sensitivity (84%) but low specificity (32%) for  diagnosis of HSV encephalitis
  • may detect non-convulsive seizures


Specific treatment

  • acyclovir 10mg/kg IV q8h (adults) for 14-21 days

Supportive care and monitoring

  • treat seizures
  • ICP monitoring and control if indicated
  • appropriate supportive care for a patient with decreased level of consciousness (e.g. airway management, pressure cares)

If bacterial meningitis is possible then also start empiric antibiotics until the diagnosis is confirmed


  • untreated: >70% mortality
  • treated: <20% mortality; 25% have epilepsy or neuropsychiatric sequelae


Diagnosis is commonly delayed

  • variable clinical presentations
  • neuropsychiatric presentations, such as amnesia
  • reluctance to perform invasive lumbar punctures in atypical presentations when utility is less certain
  • non-diagnostic investigations
    — CSF is normal in 5–10% of patients, particularly in children
    — CTB is normal in the 1st week in 1/3 patients
    — MRI brain is normal in 10%
    — PCR may be negative initially

CCC Neurocritical Care Series

Journal articles

  • Big C, Reineck LA, Aronoff DM. Viral infections of the central nervous system: a case-based review. Clin Med Res. 2009 Dec;7(4):142-6.PMC2801692.
  • Sabah M, Mulcahy J, Zeman A. Herpes simplex encephalitis. BMJ. 2012 Jun 6;344:e3166. PMID: 22674925.

FOAM and web resources

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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