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Challenges in HSV encephalitis: normocellular CSF, unremarkable CCT, and atypical MRI findings

  • Jan Philipp Bewersdorf
  • Uwe Koedel
  • Maximilian Patzig
  • Konstantinos Dimitriadis
  • Grit Paerschke
  • Hans-Walter Pfister
  • Matthias KleinEmail author
Original Paper



Herpes simplex virus (HSV) encephalitis continues to be the most common form of sporadic lethal encephalitis worldwide. The wide spectrum of clinical presentations and laboratory findings often poses a diagnostic challenge for physicians which might delay administration of life-saving therapy with acyclovir. Atypical presentations of HSV encephalitis have become increasingly prevalent with better diagnostic techniques and have not been well studied.


We retrospectively evaluated all consecutive PCR-proven HSV encephalitis cases treated at the Hospital of the Ludwig-Maximilians-University in Munich, Germany from January 1, 2013 to February 28, 2018.


We included 18 patients with PCR-proven HSV encephalitis. The most common clinical features were altered mental status (77.8%), focal neurologic deficits (72.2%) and fever (72.2%). Remarkably, four of these patients (22.2%) had a normocellular cerebrospinal fluid (CSF) on admission. Electroencephalography and magnetic resonance imaging abnormalities were highly sensitive for HSV encephalitis independent of CSF cell count. Striking atypical findings on MRI were extensive global brain swelling and severe brainstem involvement in single patients. Of note, initial CT scans were normal in 11 out of 16 patients (68.8%). All patients were treated with acyclovir. Three patients still developed a clinical deterioration under therapy with acyclovir with one patient requiring decompressive craniotomy due to bilateral space-occupying temporal lobe hemorrhage. 94.4% of the patients survived but only 38.9% were discharged with a good clinical outcome (Glasgow Outcome Score = 5).


Atypical presentations of HSV encephalitis seem to be more common than previously thought and physicians should apply a high level of clinical suspicion and a low threshold to initiate life-saving acyclovir therapy in suspected cases.


Herpes simplex virus (HSV) Encephalitis Foscarnet Acyclovir Neuroradiologic imaging Normocellular 


Author contributorship

JPB, UK, MP, HWP and MK designed the study, interpreted the data and wrote the first draft of the manuscript. KD, MP, HWP and MK were involved with clinical patient management. JPB, UK, MP, GP, HWP and MK interpreted the data and edited the manuscript. All authors reviewed and agreed on the final versions of the manuscript.


This study did not receive any specific funding.

Compliance with ethical standards

Conflict of interest

Matthias Klein has received financial support from BioMerieux. The other authors declare no financial or other conflicts of interest.

Supplementary material

15010_2018_1257_MOESM1_ESM.tif (9.1 mb)
Supplementary Fig. 1 Representative MRI images (T2 fluid-attenuated inversion recovery sequences (A) and DWI-weighted (B)) performed 6 days after symptom onset showing bilateral diffusion restrictions and swelling of the insular cortex and cingulate gyrus. (TIF 9340 KB)
15010_2018_1257_MOESM2_ESM.docx (22 kb)
Supplementary material 2 (DOCX 22 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jan Philipp Bewersdorf
    • 1
  • Uwe Koedel
    • 1
  • Maximilian Patzig
    • 2
  • Konstantinos Dimitriadis
    • 1
  • Grit Paerschke
    • 1
  • Hans-Walter Pfister
    • 1
  • Matthias Klein
    • 1
    Email author
  1. 1.Department of NeurologyKlinikum der Ludwig-Maximilians-University (LMU) MunichMunichGermany
  2. 2.Department of NeuroradiologyKlinikum der Ludwig-Maximilians-University (LMU) MunichMunichGermany

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