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Erschienen in: Journal of Neurology 7/2013

01.07.2013 | Original Communication

Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections

verfasst von: Anna Grahn, Lars Hagberg, Staffan Nilsson, Kaj Blennow, Henrik Zetterberg, Marie Studahl

Erschienen in: Journal of Neurology | Ausgabe 7/2013

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Abstract

Varicella-zoster virus (VZV) is one of our most common viruses causing central nervous system (CNS) infection with sometimes severe neurological complications. Glial fibrillary acidic protein (GFAp), light subunit of neurofilament protein (NFL) and S-100β protein are cerebrospinal fluid (CSF) biomarkers that have been used to estimate the severity of brain damage and outcome in various CNS diseases. So far, these biomarkers have not been utilised to investigate glial pathology and neuronal damage in patients with VZV CNS infections. In this prospective study, we measured CSF GFAp, NFL and S-100β as markers of brain damage in 24 patients with acute neurological manifestations and VZV DNA detected in CSF by PCR and compared with a control group (n = 14). Concentrations of CSF NFL and GFAp were increased in patients with VZV CNS infection compared with controls (p = 0.002 and p = 0.03) while levels of S-100β were reduced. In patients with VZV encephalitis the elevations of CSF NFL and GFAp were more pronounced compared with patients with other VZV CNS syndromes. No correlations between the levels of biomarkers and viral load, neurological sequels or clinical outcome were found in this limited number of patients. These results indicate that VZV induces neuronal damage and astrogliosis with more severe brain damage in patients with VZV encephalitis than in patients with other neurological complications caused by this virus.
Literatur
1.
Zurück zum Zitat De Broucker T, Mailles A, Chabrier S, Morand P, Stahl JP, Steering Committee, Investigators Group (2012) Acute varicella zoster encephalitis without evidence of primary vasculopathy in a case-series of 20 patients. Clini Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 18(8):808–819. doi:10.1111/j.1469-0691.2011.03705.x CrossRef De Broucker T, Mailles A, Chabrier S, Morand P, Stahl JP, Steering Committee, Investigators Group (2012) Acute varicella zoster encephalitis without evidence of primary vasculopathy in a case-series of 20 patients. Clini Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 18(8):808–819. doi:10.​1111/​j.​1469-0691.​2011.​03705.​x CrossRef
2.
Zurück zum Zitat Gilden D (2004) Varicella zoster virus and central nervous system syndromes. Herpes J IHMF 11(Suppl 2):89A–94A Gilden D (2004) Varicella zoster virus and central nervous system syndromes. Herpes J IHMF 11(Suppl 2):89A–94A
3.
Zurück zum Zitat Puchhammer-Stockl E, Popow-Kraupp T, Heinz FX, Mandl CW, Kunz C (1991) Detection of varicella-zoster virus DNA by polymerase chain reaction in the cerebrospinal fluid of patients suffering from neurological complications associated with chicken pox or herpes zoster. J Clin Microbiol 29(7):1513–1516PubMed Puchhammer-Stockl E, Popow-Kraupp T, Heinz FX, Mandl CW, Kunz C (1991) Detection of varicella-zoster virus DNA by polymerase chain reaction in the cerebrospinal fluid of patients suffering from neurological complications associated with chicken pox or herpes zoster. J Clin Microbiol 29(7):1513–1516PubMed
4.
Zurück zum Zitat Aberle SW, Aberle JH, Steininger C, Puchhammer-Stockl E (2005) Quantitative real time PCR detection of Varicella-zoster virus DNA in cerebrospinal fluid in patients with neurological disease. Med Microbiol Immunol 194(1–2):7–12PubMedCrossRef Aberle SW, Aberle JH, Steininger C, Puchhammer-Stockl E (2005) Quantitative real time PCR detection of Varicella-zoster virus DNA in cerebrospinal fluid in patients with neurological disease. Med Microbiol Immunol 194(1–2):7–12PubMedCrossRef
5.
Zurück zum Zitat Persson A, Bergstrom T, Lindh M, Namvar L, Studahl M (2009) Varicella-zoster virus CNS disease—viral load, clinical manifestations and sequels. J Clin Virol Off Publ Pan-Am Soc Clin Virol 46(3):249–253. doi:10.1016/j.jcv.2009.07.014 CrossRef Persson A, Bergstrom T, Lindh M, Namvar L, Studahl M (2009) Varicella-zoster virus CNS disease—viral load, clinical manifestations and sequels. J Clin Virol Off Publ Pan-Am Soc Clin Virol 46(3):249–253. doi:10.​1016/​j.​jcv.​2009.​07.​014 CrossRef
6.
Zurück zum Zitat Aurell A, Rosengren LE, Karlsson B, Olsson JE, Zbornikova V, Haglid KG (1991) Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction. Stroke J Cereb Circ 22(10):1254–1258CrossRef Aurell A, Rosengren LE, Karlsson B, Olsson JE, Zbornikova V, Haglid KG (1991) Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction. Stroke J Cereb Circ 22(10):1254–1258CrossRef
7.
Zurück zum Zitat Rosengren LE, Karlsson JE, Karlsson JO, Persson LI, Wikkelso C (1996) Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF. J Neurochem 67(5):2013–2018PubMedCrossRef Rosengren LE, Karlsson JE, Karlsson JO, Persson LI, Wikkelso C (1996) Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF. J Neurochem 67(5):2013–2018PubMedCrossRef
8.
Zurück zum Zitat Studahl M, Rosengren L, Gunther G, Hagberg L (2000) Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction. J Neurol 247(8):636–642PubMedCrossRef Studahl M, Rosengren L, Gunther G, Hagberg L (2000) Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction. J Neurol 247(8):636–642PubMedCrossRef
9.
Zurück zum Zitat Petzold A, Groves M, Leis AA, Scaravilli F, Stokic DS (2010) Neuronal and glial cerebrospinal fluid protein biomarkers are elevated after West Nile virus infection. Muscle Nerve 41(1):42–49. doi:10.1002/mus.21448 PubMedCrossRef Petzold A, Groves M, Leis AA, Scaravilli F, Stokic DS (2010) Neuronal and glial cerebrospinal fluid protein biomarkers are elevated after West Nile virus infection. Muscle Nerve 41(1):42–49. doi:10.​1002/​mus.​21448 PubMedCrossRef
11.
Zurück zum Zitat Teunissen CE, Iacobaeus E, Khademi M, Brundin L, Norgren N, Koel-Simmelink MJ, Schepens M, Bouwman F, Twaalfhoven HA, Blom HJ, Jakobs C, Dijkstra CD (2009) Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis. Neurology 72(15):1322–1329. doi:10.1212/WNL.0b013e3181a0fe3f PubMedCrossRef Teunissen CE, Iacobaeus E, Khademi M, Brundin L, Norgren N, Koel-Simmelink MJ, Schepens M, Bouwman F, Twaalfhoven HA, Blom HJ, Jakobs C, Dijkstra CD (2009) Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis. Neurology 72(15):1322–1329. doi:10.​1212/​WNL.​0b013e3181a0fe3f​ PubMedCrossRef
12.
Zurück zum Zitat Nylen K, Karlsson JE, Blomstrand C, Tarkowski A, Trysberg E, Rosengren LE (2002) Cerebrospinal fluid neurofilament and glial fibrillary acidic protein in patients with cerebral vasculitis. J Neurosci Res 67(6):844–851PubMedCrossRef Nylen K, Karlsson JE, Blomstrand C, Tarkowski A, Trysberg E, Rosengren LE (2002) Cerebrospinal fluid neurofilament and glial fibrillary acidic protein in patients with cerebral vasculitis. J Neurosci Res 67(6):844–851PubMedCrossRef
13.
Zurück zum Zitat Kaneda K, Fujita M, Yamashita S, Kaneko T, Kawamura Y, Izumi T, Tsuruta R, Kasaoka S, Maekawa T (2010) Prognostic value of biochemical markers of brain damage and oxidative stress in post-surgical aneurysmal subarachnoid hemorrhage patients. Brain Res Bull 81(1):173–177. doi:10.1016/j.brainresbull.2009.10.020 PubMedCrossRef Kaneda K, Fujita M, Yamashita S, Kaneko T, Kawamura Y, Izumi T, Tsuruta R, Kasaoka S, Maekawa T (2010) Prognostic value of biochemical markers of brain damage and oxidative stress in post-surgical aneurysmal subarachnoid hemorrhage patients. Brain Res Bull 81(1):173–177. doi:10.​1016/​j.​brainresbull.​2009.​10.​020 PubMedCrossRef
14.
Zurück zum Zitat Sindic CJ, Chalon MP, Cambiaso CL, Laterre EC, Masson PL (1982) Assessment of damage to the central nervous system by determination of S-100 protein in the cerebrospinal fluid. J Neurol Neurosurg Psychiatry 45(12):1130–1135PubMedCrossRef Sindic CJ, Chalon MP, Cambiaso CL, Laterre EC, Masson PL (1982) Assessment of damage to the central nervous system by determination of S-100 protein in the cerebrospinal fluid. J Neurol Neurosurg Psychiatry 45(12):1130–1135PubMedCrossRef
15.
Zurück zum Zitat Dotevall L, Hagberg L, Karlsson JE, Rosengren LE (1999) Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis. Eur J Neurol Off J Eur Fed Neurol Soc 6(2):169–178 Dotevall L, Hagberg L, Karlsson JE, Rosengren LE (1999) Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis. Eur J Neurol Off J Eur Fed Neurol Soc 6(2):169–178
16.
Zurück zum Zitat 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, UKHPAAoES Group (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10(12):835–844. doi:10.1016/S1473-3099(10)70222-X PubMedCrossRef 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, UKHPAAoES Group (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10(12):835–844. doi:10.​1016/​S1473-3099(10)70222-X PubMedCrossRef
17.
Zurück zum Zitat Mailles A, De Broucker T, Costanzo P, Martinez-Almoyna L, Vaillant V, Stahl JP, Steering C, Investigators G (2012) Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France. Clin Infect Dis Off Publ Infect Dis Soc Am 54(10):1455–1464. doi:10.1093/cid/cis226 CrossRef Mailles A, De Broucker T, Costanzo P, Martinez-Almoyna L, Vaillant V, Stahl JP, Steering C, Investigators G (2012) Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France. Clin Infect Dis Off Publ Infect Dis Soc Am 54(10):1455–1464. doi:10.​1093/​cid/​cis226 CrossRef
18.
Zurück zum Zitat Mailles A, Stahl JP, Steering C, Investigators G (2009) Infectious encephalitis in France in 2007: a national prospective study. Clin Infect Dis Off Publ Infect Dis Soc Am 49(12):1838–1847. doi:10.1086/648419 CrossRef Mailles A, Stahl JP, Steering C, Investigators G (2009) Infectious encephalitis in France in 2007: a national prospective study. Clin Infect Dis Off Publ Infect Dis Soc Am 49(12):1838–1847. doi:10.​1086/​648419 CrossRef
19.
Zurück zum Zitat Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1(7905):480–484PubMedCrossRef Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1(7905):480–484PubMedCrossRef
20.
Zurück zum Zitat Blennow K, Fredman P, Wallin A, Gottfries CG, Karlsson I, Langstrom G, Skoog I, Svennerholm L, Wikkelso C (1993) Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18–88 years of age. Eur Neurol 33(2):129–133PubMedCrossRef Blennow K, Fredman P, Wallin A, Gottfries CG, Karlsson I, Langstrom G, Skoog I, Svennerholm L, Wikkelso C (1993) Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18–88 years of age. Eur Neurol 33(2):129–133PubMedCrossRef
21.
Zurück zum Zitat Rosengren LE, Wikkelso C, Hagberg L (1994) A sensitive ELISA for glial fibrillary acidic protein: application in CSF of adults. J Neurosci Methods 51(2):197–204PubMedCrossRef Rosengren LE, Wikkelso C, Hagberg L (1994) A sensitive ELISA for glial fibrillary acidic protein: application in CSF of adults. J Neurosci Methods 51(2):197–204PubMedCrossRef
22.
Zurück zum Zitat Esiri MM (1982) Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain. J Neurol Sci 54(2):209–226PubMedCrossRef Esiri MM (1982) Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain. J Neurol Sci 54(2):209–226PubMedCrossRef
23.
Zurück zum Zitat Sawlani V, Gupta RK, Singh MK, Kohli A (1997) MRI demonstration of Wallerian degeneration in various intracranial lesions and its clinical implications. J Neurol Sci 146(2):103–108PubMedCrossRef Sawlani V, Gupta RK, Singh MK, Kohli A (1997) MRI demonstration of Wallerian degeneration in various intracranial lesions and its clinical implications. J Neurol Sci 146(2):103–108PubMedCrossRef
24.
25.
Zurück zum Zitat Gilden DH (2002) Varicella zoster virus vasculopathy and disseminated encephalomyelitis. J Neurol Sci 195(2):99–101PubMedCrossRef Gilden DH (2002) Varicella zoster virus vasculopathy and disseminated encephalomyelitis. J Neurol Sci 195(2):99–101PubMedCrossRef
26.
Zurück zum Zitat Miyazaki Y, Riku Y, Goto Y, Mano K, Yoshida M, Hashizume Y (2008) VZV vasculopathy associated with myelo-radiculoganglio-meningo-encephalitis: an autopsy case of an immunocompetent 66-year-old male. J Neurol Sci 275(1–2):42–45. doi:10.1016/j.jns.2008.07.019 PubMedCrossRef Miyazaki Y, Riku Y, Goto Y, Mano K, Yoshida M, Hashizume Y (2008) VZV vasculopathy associated with myelo-radiculoganglio-meningo-encephalitis: an autopsy case of an immunocompetent 66-year-old male. J Neurol Sci 275(1–2):42–45. doi:10.​1016/​j.​jns.​2008.​07.​019 PubMedCrossRef
27.
Zurück zum Zitat Gilden DH, Kleinschmidt-DeMasters BK, Wellish M, Hedley-Whyte ET, Rentier B, Mahalingam R (1996) Varicella zoster virus, a cause of waxing and waning vasculitis: the new England journal of medicine case 5–1995 revisited. Neurology 47(6):1441–1446PubMedCrossRef Gilden DH, Kleinschmidt-DeMasters BK, Wellish M, Hedley-Whyte ET, Rentier B, Mahalingam R (1996) Varicella zoster virus, a cause of waxing and waning vasculitis: the new England journal of medicine case 5–1995 revisited. Neurology 47(6):1441–1446PubMedCrossRef
28.
Zurück zum Zitat Melanson M, Chalk C, Georgevich L, Fett K, Lapierre Y, Duong H, Richardson J, Marineau C, Rouleau GA (1996) Varicella-zoster virus DNA in CSF and arteries in delayed contralateral hemiplegia: evidence for viral invasion of cerebral arteries. Neurology 47(2):569–570PubMedCrossRef Melanson M, Chalk C, Georgevich L, Fett K, Lapierre Y, Duong H, Richardson J, Marineau C, Rouleau GA (1996) Varicella-zoster virus DNA in CSF and arteries in delayed contralateral hemiplegia: evidence for viral invasion of cerebral arteries. Neurology 47(2):569–570PubMedCrossRef
29.
Zurück zum Zitat Berger TM, Caduff JH, Gebbers JO (2000) Fatal varicella-zoster virus antigen-positive giant cell arteritis of the central nervous system. Pediatr Infect Dis J 19(7):653–656PubMedCrossRef Berger TM, Caduff JH, Gebbers JO (2000) Fatal varicella-zoster virus antigen-positive giant cell arteritis of the central nervous system. Pediatr Infect Dis J 19(7):653–656PubMedCrossRef
32.
Zurück zum Zitat Fukumoto S, Kinjo M, Hokamura K, Tanaka K (1986) Subarachnoid hemorrhage and granulomatous angiitis of the basilar artery: demonstration of the varicella-zoster-virus in the basilar artery lesions. Stroke J Cereb Circ 17(5):1024–1028CrossRef Fukumoto S, Kinjo M, Hokamura K, Tanaka K (1986) Subarachnoid hemorrhage and granulomatous angiitis of the basilar artery: demonstration of the varicella-zoster-virus in the basilar artery lesions. Stroke J Cereb Circ 17(5):1024–1028CrossRef
33.
Zurück zum Zitat Takashima S, Becker LE (1979) Neuropathology of fatal varicella. Arch Pathol Lab Med 103(5):209–213PubMed Takashima S, Becker LE (1979) Neuropathology of fatal varicella. Arch Pathol Lab Med 103(5):209–213PubMed
34.
Zurück zum Zitat 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(11):853–860PubMedCrossRef 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(11):853–860PubMedCrossRef
35.
Zurück zum Zitat Sjogren M, Blomberg M, Jonsson M, Wahlund LO, Edman A, Lind K, Rosengren L, Blennow K, Wallin A (2001) Neurofilament protein in cerebrospinal fluid: a marker of white matter changes. J Neurosci Res 66(3):510–516PubMedCrossRef Sjogren M, Blomberg M, Jonsson M, Wahlund LO, Edman A, Lind K, Rosengren L, Blennow K, Wallin A (2001) Neurofilament protein in cerebrospinal fluid: a marker of white matter changes. J Neurosci Res 66(3):510–516PubMedCrossRef
36.
Zurück zum Zitat Ming JE, Stiehm ER, Graham JM Jr (1999) Syndromes associated with immunodeficiency. Adv Pediatr 46:271–351PubMed Ming JE, Stiehm ER, Graham JM Jr (1999) Syndromes associated with immunodeficiency. Adv Pediatr 46:271–351PubMed
37.
Zurück zum Zitat Devinsky O, Cho ES, Petito CK, Price RW (1991) Herpes zoster myelitis. Brain J Neurol 114(Pt 3):1181–1196CrossRef Devinsky O, Cho ES, Petito CK, Price RW (1991) Herpes zoster myelitis. Brain J Neurol 114(Pt 3):1181–1196CrossRef
38.
Zurück zum Zitat Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E (2009) Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol 81(8):1432–1437. doi:10.1002/jmv.21563 PubMedCrossRef Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E (2009) Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol 81(8):1432–1437. doi:10.​1002/​jmv.​21563 PubMedCrossRef
Metadaten
Titel
Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections
verfasst von
Anna Grahn
Lars Hagberg
Staffan Nilsson
Kaj Blennow
Henrik Zetterberg
Marie Studahl
Publikationsdatum
01.07.2013
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 7/2013
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-013-6883-5

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