Herpes simplex encephalitis

Last updated: November 20, 2023

Summarytoggle arrow icon

Herpes simplex encephalitis (HSE) is an inflammation of the brain parenchyma, typically in the medial temporal lobe, that is caused by either herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2). It is the most common cause of fatal sporadic encephalitis in the US. HSE has a bimodal distribution, commonly affecting patients younger than 20 years of age and older than 50 years of age. Patients with HSE typically present with a prodrome of headaches and fever, followed by sudden focal neurological deficits, altered mental status, and possible seizures. Characteristic clinical findings and brain imaging showing temporal lesions should raise suspicion for HSE. Lumbar puncture often reveals lymphocytic pleocytosis. The diagnosis is best confirmed with polymerase chain reaction (PCR) testing of cerebrospinal fluid. Because HSE has a rapidly progressive and potentially fatal course, treatment with acyclovir should begin as soon as the disease is suspected. The mortality rate is as high as 70% if left untreated, and relapse is possible but uncommon.

Epidemiologytoggle arrow icon


Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon


Pathophysiologytoggle arrow icon


Clinical featurestoggle arrow icon

Prodromal phase

Acute or subacute encephalopathy

HSE may resemble bacterial meningitis, but the combination of altered mental status, seizures, and focal neurological deficits is more common for HSE!


Diagnosticstoggle arrow icon

Approach [7][8]

Empiric treatment should be initiated while awaiting the definitive diagnosis, as the progression of HSE is very rapid. [7][10]

Laboratory studies [7][11]

Blood studies

CSF studies [7][8]

CSF analysis in herpes simplex encephalitis [7][10]
CSF parameters Findings
Cell count and differential
Opening pressure
  • Normal or ↑
  • Variable, normal to mild
  • Mild ↑
  • Normal (or similar to serum glucose)

Neuroimaging [7]

Always consider HSE when imaging suggests potential meningoencephalitis and temporal lobe involvement; bilateral temporal lobe abnormality is a pathognomic sign of HSE. [7]

Electroencephalography (EEG) [7]

  • Indication: all patients with suspected HSE
  • Findings
    • Abnormal in > 80% of patients [10]
    • Characteristic finding: periodic lateralized epileptiform discharges from the affected temporal lobe

Pathologytoggle arrow icon

  • Macroscopic: typical temporal lobe distribution with visible necrosis
  • Microscopic
    • Hemorrhagic-necrotizing inflammation
    • Eosinophilic nuclear inclusions (Cowdry bodies)

References: [14]

Treatmenttoggle arrow icon

Antimicrobial treatment for herpes simplex encephalitis [7][9][10]

All patients should be hospitalized and a neurology consult is highly recommended; intensive care must be readily available. [13]

Monitor for nephrotoxicity during treatment with acyclovir. Manage with adequate hydration and adjust dosages for renal function. [8][10]

Management of complications

Acute management checklist for herpes simplex encephalitis

Prognosistoggle arrow icon

  • Fatal in up to 70% of cases if left untreated [2]
  • In patients receiving treatment, the mortality rate is still as high as 20–30%. [3]
  • Relapse may occur.
  • Residual deficits may remain in some cases (e.g., paresis, cognitive deficits, psychopathological symptoms)

Preventiontoggle arrow icon

Referencestoggle arrow icon

  1. Anderson WE. Herpes Simplex Encephalitis. In: Singh NN, Herpes Simplex Encephalitis. New York, NY: WebMD. Updated: June 15, 2016. Accessed: November 6, 2016.
  2. Shorvon SD, Andermann F, Guerrini R. The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children. Cambridge University Press ; 2011: p. 468
  3. Klein RS. Herpes simplex virus type 1 encephalitis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: August 15, 2014. Accessed: November 6, 2016.
  4. Anderson WE. Herpes Simplex Encephalitis. In: Singh NN, Herpes Simplex Encephalitis. New York, NY: WebMD. Updated: June 15, 2016. Accessed: November 2, 2016.
  5. Anderson WE. Herpes Simplex Encephalitis Clinical Presentation. In: Singh NN, Herpes Simplex Encephalitis Clinical Presentation. New York, NY: WebMD. Updated: June 15, 2016. Accessed: November 6, 2016.
  6. Anderson WE. Herpes Simplex Encephalitis. In: Singh NN, Herpes Simplex Encephalitis. New York, NY: WebMD. Updated: June 15, 2016. Accessed: November 6, 2016.
  7. Tunkel AR, Glaser CA, Bloch KC, et al. The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2008; 47 (3): p.303-327.doi: 10.1086/589747 . | Open in Read by QxMD
  8. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical ; 2018
  9. Stahl JP, Mailles A. Herpes simplex virus encephalitis update. Current Opinion in Infectious Diseases. 2019; 32 (3): p.239-243.doi: 10.1097/qco.0000000000000554 . | Open in Read by QxMD
  10. Gnann JW, Whitley RJ. Herpes Simplex Encephalitis: an Update. Current Infectious Diseases Reports. 2017; 19 (3).doi: 10.1007/s11908-017-0568-7 . | Open in Read by QxMD
  11. Walls R, Hockberger R, Gausche-Hill M. Rosen's Emergency Medicine. Elsevier Health Sciences ; 2018
  12. Chaudhuri A, Kennedy PGE. Diagnosis and treatment of viral encephalitis. Postgraduate Medical Journal. 2002; 78 (924): p.575-583.doi: 10.1136/pmj.78.924.575 . | Open in Read by QxMD
  13. Steiner I, Budka H, Chaudhuri A, et al. Viral encephalitis: a review of diagnostic methods and guidelines for management. European Journal of Neurology. 2005; 12 (5): p.331-343.doi: 10.1111/j.1468-1331.2005.01126.x . | Open in Read by QxMD
  14. Patel MR. Imaging in Herpes Encephalitis. In: Smirniotopoulos JG, Imaging in Herpes Encephalitis. New York, NY: WebMD. Updated: July 14, 2015. Accessed: November 6, 2016.
  15. Gilbert, DN; Chambers, HF. Sanford Guide to Antimicrobial Therapy 2020. Antimicrobial Therapy, Inc ; 2020
  16. Bergmann M, Beer R, Kofler M, Helbok R, Pfausler B, Schmutzhard E. Acyclovir resistance in herpes simplex virus type I encephalitis: a case report. Journal of Neurovirology. 2016; 23 (2): p.335-337.doi: 10.1007/s13365-016-0489-5 . | Open in Read by QxMD
  17. Schulte EC, Sauerbrei A, Hoffmann D, Zimmer C, Hemmer B, Mühlau M. Acyclovir resistance in herpes simplex encephalitis. Annals of Neurology. 2010; 67 (6): p.830-833.doi: 10.1002/ana.21979 . | Open in Read by QxMD
  18. Pandey S, Rathore C, Michael BD. Antiepileptic drugs for the primary and secondary prevention of seizures in viral encephalitis. Cochrane Database of Systematic Reviews. 2016.doi: 10.1002/14651858.cd010247.pub3 . | Open in Read by QxMD
  19. AK AK, Mendez MD. Herpes Simplex Encephalitis. StatPearls. 2021.
  20. Venkatesan A, Geocadin RG. Diagnosis and management of acute encephalitis: A practical approach. Neurology: Clinical Practice. 2014; 4 (3): p.206-215.doi: 10.1212/cpj.0000000000000036 . | Open in Read by QxMD

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