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A study on viral CNS inflammation beyond herpes encephalitis

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Abstract

The early diagnosis of herpes simplex virus encephalitis (HSVE) enables induction of antiviral therapy in this potentially life-threatening disease. The study aimed to determine clinical findings including cerebrospinal fluid (CSF) data and MRI imaging in HSVE patients and to identify features distinguishing HSVE from encephalitis of other viral etiologies. We retrospectively reviewed consecutive patients who were diagnosed with viral encephalitis between 2000 and 2014 at the University Hospital Halle. Forty-nine patients with viral encephalitis were identified. A viral etiology could be confirmed by PCR or antibody testing in 22/49 (44.9 %) of patients (15 (30.6 %) HSV, 5 (10.2 %) VZV, 2 (4.1 %) EBV). In HSVE, typical findings were focal slowing in electroencephalophy (EEG) (80 %, p = 0.021) and presence of cortical (86.7 %, p = 0.030) lesions in MRI. Restricted diffusion was particularly helpful in detection of early signal abnormalities in HSVE (p = 0.014). In 27/49 (55.1 %) of patients, no causative agent could be elucidated. In these patients, 15/27 (55.6 %) experienced a rather “benign” disease course with no MRI pathology despite initially HSVE mimicking clinical picture. However, CSF was significantly different showing a higher amount of granulocytes and activated lymphocytes. The remaining 12/27 (44.4 %) patients developed MRI changes consistent with encephalitis, in 4 of these patients, disease course was fatal. Beside PCR-based serology as standard procedure, MRI including diffusion-weighted images and EEG represent additional tools in early HSVE diagnosis. CSF cytology might be particularly supportive in differentiating likely benign forms of encephalitis.

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References

  • Akyldz BN, Gumus H, Kumandas S, Coskun A, Karakukucu M, Yklmaz A (2008) Diffusion-weighted magnetic resonance is better than polymerase chain reaction for early diagnosis of herpes simplex encephalitis: a case report. Pediatr Emerg Care 24:377–379

    Article  PubMed  Google Scholar 

  • Bloch KC, Glaser C (2007) Diagnostic approaches for patients with suspected encephalitis. Curr Infect Dis Rep 9:315–322

    Article  PubMed  Google Scholar 

  • Bulakbasi N, Kocaoglu M (2008) Central nervous system infections of herpesvirus family. Neuroimaging Clin N Am 18:53–84, viii

    Article  PubMed  Google Scholar 

  • Chow FC, Glaser CA, Sheriff H, Xia D, Messenger S, Whitley R, Venkatesan A (2015) Use of clinical and neuroimaging characteristics to distinguish temporal lobe herpes simplex encephalitis from its mimics. Clin Infect Dis 60:1377–1383

    PubMed  PubMed Central  Google Scholar 

  • De Broucker T, Mailles A, Chabrier S, Morand P, Stahl JP, Steering C, Investigators G (2012) Acute varicella zoster encephalitis without evidence of primary vasculopathy in a case-series of 20 patients. Clin Microbiol Infect 18:808–819

    Article  PubMed  Google Scholar 

  • Domingues RB, Fink MC, Tsanaclis AM, de Castro CC, Cerri GG, Mayo MS, Lakeman FD (1998) Diagnosis of herpes simplex encephalitis by magnetic resonance imaging and polymerase chain reaction assay of cerebrospinal fluid. J Neurol Sci 157:148–153

    Article  CAS  PubMed  Google Scholar 

  • Dubberke ER, Tu B, Rivet DJ, Storch GA, Apisarnthanarak A, Schmidt RE, Weiss S, Polish LB (2006) Acute meningoencephalitis caused by adenovirus serotype 26. J Neurovirol 12:235–240

    Article  PubMed  Google Scholar 

  • Frantzidou F, Kamaria F, Dumaidi K, Skoura L, Antoniadis A, Papa A (2008) Aseptic meningitis and encephalitis because of herpesviruses and enteroviruses in an immunocompetent adult population. Eur J Neurol 15:995–997

    Article  CAS  PubMed  Google Scholar 

  • George BP, Schneider EB, Venkatesan A (2014) Encephalitis hospitalization rates and inpatient mortality in the United States, 2000–2010. PLoS One 9:e104169

    Article  PubMed  PubMed Central  Google Scholar 

  • Gilden D, Cohrs RJ, Mahalingam R, Nagel MA (2009) Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol 8:731–740

    Article  PubMed  PubMed Central  Google Scholar 

  • Grahn A, Studahl M (2015) Varicella-zoster virus infections of the central nervous system—prognosis, diagnostics and treatment. J Infect 71:281–293

    Article  PubMed  Google Scholar 

  • Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, Cunningham R, Zuckerman M, Mutton KJ, Solomon T, Ward KN, Lunn MP, Irani SR, Vincent A, Brown DW, Crowcroft NS, Group UKHPAAoES (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10:835–844

    Article  PubMed  Google Scholar 

  • Hoffmann B, Tappe D, Hoper D, Herden C, Boldt A, Mawrin C, Niederstrasser O, Muller T, Jenckel M, van der Grinten E, Lutter C, Abendroth B, Teifke JP, Cadar D, Schmidt-Chanasit J, Ulrich RG, Beer M (2015) A variegated squirrel bornavirus associated with fatal human encephalitis. N Engl J Med 373:154–162

    Article  CAS  PubMed  Google Scholar 

  • Hollinger P, Matter L, Sturzenegger M (2000) Normal MRI findings in herpes simplex virus encephalitis. J Neurol 247:799–801

    Article  CAS  PubMed  Google Scholar 

  • Jakob NJ, Lenhard T, Schnitzler P, Rohde S, Ringleb PA, Steiner T, Wildemann B (2012) Herpes simplex virus encephalitis despite normal cell count in the cerebrospinal fluid. Crit Care Med 40:1304–1308

    Article  PubMed  Google Scholar 

  • Kennedy PG, Steiner I (2013) Recent issues in herpes simplex encephalitis. J Neurovirol 19:346–350

    Article  PubMed  Google Scholar 

  • Kiroglu Y, Calli C, Yunten N, Kitis O, Kocaman A, Karabulut N, Isaev H, Yagci B (2006) Diffusion-weighted MR imaging of viral encephalitis. Neuroradiology 48:875–880

    Article  PubMed  Google Scholar 

  • Koskiniemi M, Rantalaiho T, Piiparinen H, von Bonsdorff CH, Farkkila M, Jarvinen A, Kinnunen E, Koskiniemi S, Mannonen L, Muttilainen M, Linnavuori K, Porras J, Puolakkainen M, Raiha K, Salonen EM, Ukkonen P, Vaheri A, Valtonen V, Study G (2001) Infections of the central nervous system of suspected viral origin: a collaborative study from Finland. J Neurovirol 7:400–408

    Article  CAS  PubMed  Google Scholar 

  • Kuker W, Nagele T, Schmidt F, Heckl S, Herrlinger U (2004) Diffusion-weighted MRI in herpes simplex encephalitis: a report of three cases. Neuroradiology 46:122–125

    Article  CAS  PubMed  Google Scholar 

  • Lakeman FD, Whitley RJ (1995) Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis 171:857–863

    Article  CAS  PubMed  Google Scholar 

  • Long SS (2011) Encephalitis diagnosis and management in the real world. Adv Exp Med Biol 697:153–173

    Article  PubMed  Google Scholar 

  • Maschke M, Kastrup O, Forsting M, Diener HC (2004) Update on neuroimaging in infectious central nervous system disease. Curr Opin Neurol 17:475–480

    Article  PubMed  Google Scholar 

  • McCabe K, Tyler K, Tanabe J (2003) Diffusion-weighted MRI abnormalities as a clue to the diagnosis of herpes simplex encephalitis. Neurology 61:1015–1016

    Article  PubMed  Google Scholar 

  • Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, Safdieh JE, Kamenkovich E, Ostrow LW, Levy M, Greenberg B, Russman AN, Katzan I, Gardner CJ, Hausler M, Nau R, Saraya T, Wada H, Goto H, de Martino M, Ueno M, Brown WD, Terborg C, Gilden DH (2008) The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 70:853–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oyanguren B, Sanchez V, Gonzalez FJ, de Felipe A, Esteban L, Lopez-Sendon JL, Garcia-Barragan N, Martinez-San Millan J, Masjuan J, Corral I (2013) Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies. Eur J Neurol 20:1566–1570

    Article  CAS  PubMed  Google Scholar 

  • Perneger TV (1998) What's wrong with Bonferroni adjustments. BMJ 316:1236–1238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raschilas F, Wolff M, Delatour F, Chaffaut C, De Broucker T, Chevret S, Lebon P, Canton P, Rozenberg F (2002) Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis 35:254–260

    Article  PubMed  Google Scholar 

  • Renard D, Nerrant E, Lechiche C (2015) DWI and FLAIR imaging in herpes simplex encephalitis: a comparative and topographical analysis. J Neurol 262:2101–2105

    Article  CAS  PubMed  Google Scholar 

  • Sawlani V (2009) Diffusion-weighted imaging and apparent diffusion coefficient evaluation of herpes simplex encephalitis and Japanese encephalitis. J Neurol Sci 287:221–226

    Article  PubMed  Google Scholar 

  • Sheybani F, Arabikhan HR, Naderi HR (2013) Herpes simplex encephalitis (HSE) and its outcome in the patients who were admitted to a tertiary care hospital in Mashhad, Iran, over a 10-year period. J Clin Diagn Res 7:1626–1628

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sili U, Kaya A, Mert A, Group HSVES (2014) Herpes simplex virus encephalitis: clinical manifestations, diagnosis and outcome in 106 adult patients. J Clin Virol 60:112–118

    Article  PubMed  Google Scholar 

  • Singh TD, Fugate JE, Rabinstein AA (2015) The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology 84:359–366

    Article  CAS  PubMed  Google Scholar 

  • Singh TD, Fugate JE, Hocker S, Wijdicks EF, Aksamit AJ Jr, Rabinstein AA (2016) Predictors of outcome in HSV encephalitis. J Neurol 263:277–289

    Article  CAS  PubMed  Google Scholar 

  • Solomon T, Michael BD, Smith PE, Sanderson F, Davies NW, Hart IJ, Holland M, Easton A, Buckley C, Kneen R, Beeching NJ, National Encephalitis Guidelines D, Stakeholder G (2012) Management of suspected viral encephalitis in adults—Association of British Neurologists and British Infection Association National Guidelines. J Infect 64:347–373

    Article  CAS  PubMed  Google Scholar 

  • Sonneville R, Gault N, de Montmollin E, Klein IF, Mariotte E, Chemam S, Tubach F, Mourvillier B, Timsit JF, Wolff M, Bouadma L (2015) Clinical spectrum and outcomes of patients with encephalitis requiring intensive care. Eur J Neurol 22(6–16):e1

    Google Scholar 

  • Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O, Kennedy PG (2010) Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol 17:999–e57

    Article  CAS  PubMed  Google Scholar 

  • Steiner I, Schmutzhard E, Sellner J, Chaudhuri A, Kennedy PG, European Federation of Neurological S, European Neurologic S (2012) EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections of the nervous system. Eur J Neurol 19:1278–1291

    Article  CAS  PubMed  Google Scholar 

  • Stretz C, Finelli PF (2015) Differential Diagnosis of Restricted Diffusion of the Thalamus–—Focus on Viral Encephalitis. Neurohospitalist 5:NP1–NP2

    Article  PubMed  PubMed Central  Google Scholar 

  • Tsuchiya K, Katase S, Yoshino A, Hachiya J (1999) Diffusion-weighted MR imaging of encephalitis. AJR Am J Roentgenol 173:1097–1099

    Article  CAS  PubMed  Google Scholar 

  • van Zeijl JH, Bakkers J, Wilbrink B, Melchers WJ, Mullaart RA, Galama JM (2005) Influenza-associated encephalopathy: no evidence for neuroinvasion by influenza virus nor for reactivation of human herpesvirus 6 or 7. Clin Infect Dis 40:483–485

    Article  PubMed  Google Scholar 

  • Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA, International Encephalitis C (2013) Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 57:1114–1128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vora NM, Holman RC, Mehal JM, Steiner CA, Blanton J, Sejvar J (2014) Burden of encephalitis-associated hospitalizations in the United States, 1998–2010. Neurology 82:443–451

    Article  PubMed  Google Scholar 

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Correspondence to Berit Jordan.

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Jordan, B., Kösling, S., Emmer, A. et al. A study on viral CNS inflammation beyond herpes encephalitis. J. Neurovirol. 22, 763–773 (2016). https://doi.org/10.1007/s13365-016-0452-5

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  • DOI: https://doi.org/10.1007/s13365-016-0452-5

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