HSV Encephalitis

Reviewed and revised 2 February 2014

OVERVIEW

• 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

CAUSE

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

CLINICAL FEATURES

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

INVESTIGATIONS

Approach

• 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
• HSV PCR
  — 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

Electroencephalography

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

MANAGEMENT

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

PROGNOSIS

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

OTHER INFORMATION

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

References and Links

LITFL

• CCC — Encephalitis
• CCC — Anti-NMDA Receptor Encephalitis

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

• Radiopaedia.org — HSV encephalitis