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Herpes Simplex Virus (HSV) encephalitis

Summary

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  • Acute necrotizing encephalitis caused by HSV-1 or HSV-2
  • Typically affects temporal and frontal lobes
  • Characterised by fever, altered mental status, and focal neurological deficits1

Pathophysiology

  • HSV-1 is the most common cause in adults (90% of cases)
  • HSV-2 more common in neonates and immunocompromised individuals
  • Virus enters via olfactory or trigeminal nerve pathways
  • Causes cytotoxic and vasogenic oedema, haemorrhage, and necrosis
  • Predilection for limbic structures, particularly temporal lobes

Demographics

  • Incidence: 2-4 cases per million per year
  • Bimodal age distribution:
    • Peak in young adults (20-30 years)
    • Second peak in older adults (>50 years)
  • No gender predilection
  • Can occur in all age groups, including neonates

Diagnosis

  • Clinical presentation:
    • Fever, headache, altered mental status
    • Focal neurological deficits (e.g., aphasia, hemiparesis)
    • Seizures (70% of cases)
  • Laboratory findings:
    • CSF analysis: pleocytosis, elevated protein, normal glucose
    • PCR detection of HSV DNA in CSF (sensitivity >95%, specificity >99%)
  • EEG: periodic lateralized epileptiform discharges (PLEDs)

Imaging

  • CT findings:
    • Early: normal or subtle low attenuation in affected areas
    • Late: haemorrhage, contrast enhancement, mass effect
  • MRI findings (more sensitive than CT):
    • T2/FLAIR: hyperintense signal in affected regions
    • DWI: restricted diffusion in acute phase
    • T1 post-contrast: gyral enhancement
    • SWI: petechial haemorrhages
  • Typical distribution:
    • Asymmetric involvement of temporal lobes (95% of cases)
    • Frontal lobe involvement (80% of cases)
    • Insular cortex, cingulate gyrus may be affected
    • Sparing of basal ganglia

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  • 50-year-old patient presented with headache and confusion.
  • CT showed swelling and low attenuation in the anterior and mesial left temporal lobe and in the right hippocampus.
  • The parenchymal low attenuation gave the impression of a hyperdense vessel (Mach effect) but infarction was not likely as both MCA and PCA territories were involved.
  • There was high T2, FLAIR and DWI signal (without clear diffusion restriction) but no enhancement.

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  • 40-year-old patient presented with 2 day history of confusion and reduced GCS, headache and fever.
  • MRI showed hyperintensity and swelling of the right mesial temporal lobe and diffusion restriction extending up to the right parietal lobe.

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  • 70-year-old patient presented with dysphasia and right-sided weakness and seizures. HSV was identified in CSF.
  • MRI showed diffusion restriction in the cortex of left cerebral hemisphere as well as the right insula. There was swelling and subtle cortical enhancement.

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  • 60-year-old patient presented with expressive dysphasia.
  • MRI showed diffuse patchy cortical, white matter and ganglionic hyperintensity.
  • On follow-up, hyperintensity involving most of the left temporal lobe resolved while marked hyperintensity developed in the right temporal lobe.
  • Despite being repeatedly negative on CSF, brain biopsy revealed an HSV encephalitis.

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  • 75-year-old patient presented with dysphasia and right sided weakness.
  • MRI showed cortical DWI hyperintensity in the left frontal, parietal, temporal lobes and insular cortex bilaterally.
  • Initially concerned about an acute infarct, the widespread and exclusively cortical involvement and a normal CTA, made HSV encephalitis more likely (which was confirmed on CSF analysis).

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  • A 45-year-old patient presented with right sided weakness and a fever.
  • CT showed a haematoma in the left paramedian frontal lobe.
  • MRI showed oedema around the haematoma as well as subtle high FLAIR signal in the cortex of the left frontal lobe and the right cingulate.
  • On follow-up imaging, the FLAIR hyperintensity (and diffusion restriction) had extended through the limbic system.
  • CSF HSV-1 PCR was positive.

Treatment

  • Empirical IV aciclovir must be started on suspicion, before confirmation, as early treatment dramatically reduces mortality

Differential diagnosis

Differential Diagnosis Differentiating Feature
Autoimmune limbic encephalitis Bilateral mesial temporal FLAIR hyperintensity without haemorrhage; typically no cortical ribboning on DWI; may enhance
MCA infarction Confined to MCA vascular territory; involves basal ganglia; no involvement of contralateral mesial temporal lobe
Gliomatosis cerebri / low-grade glioma Infiltrative T2 signal without swelling or DWI restriction; no cortical haemorrhage or gyral enhancement
Neurosyphilis Mesiotemporal T2 hyperintensity similar to HSV; leptomeningeal and cortical enhancement; infarcts from vasculitis
Other viral encephalitides (HHV-6, VZV, EBV) Similar mesiotemporal involvement; indistinguishable on imaging alone

  1. Si et al. Analysis of Metagenomic Next-Generation Sequencing (mNGS) in the Diagnosis of Herpes Simplex Virus (HSV) Encephalitis with Normal Cerebrospinal Fluid (CSF). 2023. Infection and drug resistance - Open in new tab. ↩