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Infection

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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 Klein
Original Paper
  • 57 Downloads

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusion

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.

Keywords

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

Notes

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.

Funding

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)

References

  1. 1.
    Hasbun R, Rosenthal N, Balada-Llasat JM, Chung J, Duff S, Bozzette S, et al. Epidemiology of meningitis and encephalitis in the United States, 2011–2014. Clin Infect Dis. 2017;65:359–63.CrossRefPubMedGoogle Scholar
  2. 2.
    Jouan Y, Grammatico-Guillon L, Espitalier F, Cazals X, Francois P, Guillon A. Long-term outcome of severe herpes simplex encephalitis: a population-based observational study. Crit Care. 2015;19:345.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Whitley RJ, Soong SJ, Dolin R, Galasso GJ, Ch’ien LT, Alford CA. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med. 1977;297:289–94.CrossRefPubMedGoogle Scholar
  4. 4.
    Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10:835–44.CrossRefPubMedGoogle Scholar
  5. 5.
    Gnann JW Jr, Skoldenberg B, Hart J, Aurelius E, Schliamser S, Studahl M, et al. Herpes simplex encephalitis: lack of clinical benefit of long-term valacyclovir therapy. Clin Infect Dis. 2015;61:683–91.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013;57:1114–28.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Sili U, Kaya A, Mert A, Group HSVES. Herpes simplex virus encephalitis: clinical manifestations, diagnosis and outcome in 106 adult patients. J Clin Virol. 2014;60:112–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Hebant B, Miret N, Bouwyn JP, Delafosse E, Lefaucheur R. Absence of pleocytosis in cerebrospinal fluid does not exclude herpes simplex virus encephalitis in elderly adults. J Am Geriatr Soc. 2015;63:1278–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Saraya AW, Wacharapluesadee S, Petcharat S, Sittidetboripat N, Ghai S, Wilde H, et al. Normocellular CSF in herpes simplex encephalitis. BMC Res Notes. 2016;9:95.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Whitley RJ, Cobbs CG, Alford CA Jr, Soong SJ, Hirsch MS, Connor JD, et al. Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group. JAMA. 1989;262:234–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Gordon CL, Johnson PD, Permezel M, Holmes NE, Gutteridge G, McDonald CF, et al. Association between severe pandemic 2009 influenza A (H1N1) virus infection and immunoglobulin G(2) subclass deficiency. Clin Infect Dis. 2010;50:672–8.PubMedGoogle Scholar
  12. 12.
    Bass JL, Nuss R, Mehta KA, Morganelli P, Bennett L. Recurrent meningococcemia associated with IgG2-subclass deficiency. N Engl J Med. 1983;309:430.PubMedGoogle Scholar
  13. 13.
    Escobar-Perez X, Dorta-Contreras AJ, Interian-Morales MT, Noris-Garcia E, Ferra-Valdes M. IgG2 immunodeficiency: association to pediatric patients with bacterial meningoencephalitis. Arq Neuropsiquiatr. 2000;58:141–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Tan IL, McArthur JC, Venkatesan A, Nath A. Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology. 2012;79:2125–32.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Granerod J, Davies NW, Mukonoweshuro W, Mehta A, Das K, Lim M, et al. Neuroimaging in encephalitis: analysis of imaging findings and interobserver agreement. Clin Radiol. 2016;71:1050–8.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Misra UK, Kalita J. Seizures in encephalitis: predictors and outcome. Seizure. 2009;18:583–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Chow FC, Glaser CA, Sheriff H, Xia D, Messenger S, Whitley R, et al. Use of clinical and neuroimaging characteristics to distinguish temporal lobe herpes simplex encephalitis from its mimics. Clin Infect Dis. 2015;60:1377–83.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Garg M, Kulkarni S, Udwadia Hegde A. Herpes simplex encephalitis with thalamic, brainstem and cerebellar involvement. Neuroradiol J. 2018;31:190–2.CrossRefPubMedGoogle Scholar
  19. 19.
    Katchanov J, Branding G, Stocker H. Combined CMV- and HSV-1 brainstem encephalitis restricted to medulla oblongata. J Neurol Sci. 2014;339:229–30.CrossRefPubMedGoogle Scholar
  20. 20.
    Miura S, Kurita T, Noda K, Ayabe M, Aizawa H, Taniwaki T. Symmetrical brainstem encephalitis caused by herpes simplex virus. J Clin Neurosci. 2009;16:589–90.CrossRefPubMedGoogle Scholar
  21. 21.
    Mitterreiter JG, Titulaer MJ, van Nierop GP, van Kampen JJ, Aron GI, Osterhaus AD, et al. Prevalence of intrathecal acyclovir resistant virus in herpes simplex encephalitis patients. PLoS One. 2016;11:e0155531.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Karrasch M, Liermann K, Betz BB, Wagner S, Scholl S, Dahms C, et al. Rapid acquisition of acyclovir resistance in an immunodeficient patient with herpes simplex encephalitis. J Neurol Sci. 2018;384:89–90.CrossRefPubMedGoogle Scholar
  23. 23.
    ElShimy G, Mariyam Joy C, Berlin F, Lashin W. Intracranial hemorrhage complicating herpes simplex encephalitis on antiviral therapy: a case report and review of the literature. Case Rep Infect Dis. 2017;2017:6038146.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Harada Y, Hara Y. Herpes simplex encephalitis complicated by cerebral hemorrhage during acyclovir therapy. Intern Med. 2017;56:225–9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Rodriguez-Sainz A, Escalza-Cortina I, Guio-Carrion L, Matute-Nieves A, Gomez-Beldarrain M, Carbayo-Lozano G, et al. Intracerebral hematoma complicating herpes simplex encephalitis. Clin Neurol Neurosurg. 2013;115:2041–5.CrossRefPubMedGoogle Scholar

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
  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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