Herpes simplex virus encephalitis: clinical manifestations, diagnosis and outcome in 106 adult patients

J Clin Virol. 2014 Jun;60(2):112-8. doi: 10.1016/j.jcv.2014.03.010. Epub 2014 Mar 25.


Background: Herpes simplex virus (HSV) is one of the most common causes of sporadic encephalitis worldwide.

Objective: We aimed to determine clinical characteristics and prognosis of HSV encephalitis (HSVE) cases reviewed retrospectively from several collaborating centers.

Study design: We searched hospital archives of the last 10 years for patients with HSVE diagnosis, i.e. clinical presentation compatible with encephalitis and brain involvement on magnetic resonance imaging (MRI) and/or detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Clinical characteristics were noted and patients were phone-interviewed. HSVE cases were grouped and analyzed as proven and probable, based on virological confirmation by PCR. Univariate and multivariate analyses were used to determine factors associated with prognosis.

Results: A total of 106 patients (63 males and 43 females; mean age, 44 years; range, 18-83 years) were included. Most common symptoms were changes in mental status, fever, headache, and seizure. HSV PCR was positive in 69% of patients tested, while brain involvement was detected on MRI in 95%. Acyclovir was started mostly within five days of main symptom and continued for ≥14 days. Case fatality rate was 8%, while 69% of patients recovered with sequelae. Favorable prognosis was observed in 73% of patients. Multivariate analysis identified the duration of disease before hospital admission (odds ratio (OR)=1.24) and the extent of brain involvement on MRI at the time of admission (OR=37.22) as two independent risk factors associated with poor prognosis.

Conclusions: Although HSVE fatality regressed considerably with acyclovir treatment, many patients survive with sequelae. Our results emphasize the importance of early diagnosis and prompt treatment of HSVE.

Keywords: Herpes simplex virus; prognostic factors; viral encephalitis.

Publication types

  • Multicenter Study

MeSH terms

  • Acyclovir / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cerebrospinal Fluid / virology
  • DNA, Viral / cerebrospinal fluid
  • Encephalitis, Herpes Simplex / diagnosis*
  • Encephalitis, Herpes Simplex / drug therapy
  • Encephalitis, Herpes Simplex / pathology*
  • Female
  • Humans
  • Interviews as Topic
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Radiography
  • Retrospective Studies
  • Simplexvirus / isolation & purification*
  • Treatment Outcome
  • Young Adult


  • Antiviral Agents
  • DNA, Viral
  • Acyclovir