Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-20T04:54:57.806Z Has data issue: false hasContentIssue false
  • English
  • Français

Cerebrospinal fluid biomarkers in patients with central nervous system infections: a retrospective study

Published online by Cambridge University Press:  27 May 2019

Alessandro Di Stefano Open the ORCID record for Alessandro Di Stefano [Opens in a new window] ,
Chiara Alcantarini ,
Cristiana Atzori ,
Filippo Lipani ,
Daniele Imperiale ,
Elisa Burdino ,
Sabrina Audagnotto ,
Lorenzo Mighetto ,
Maria Grazia Milia  and
Giovanni Di Perri
...Show all authors
Alessandro Di Stefano*
Affiliation:
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy
Chiara Alcantarini
Affiliation:
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy
Cristiana Atzori
Affiliation:
Unit of Neurology, Ospedale Maria Vittoria, ASL TO2, Torino, Italy
Filippo Lipani
Affiliation:
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy
Daniele Imperiale
Affiliation:
Unit of Neurology, Ospedale Maria Vittoria, ASL TO2, Torino, Italy
Elisa Burdino
Affiliation:
Laboratory of Microbiology and Molecular Biology, Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy
Sabrina Audagnotto
Affiliation:
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy
Lorenzo Mighetto
Affiliation:
Biochemistry and Immunology Laboratory, Ospedale Maria Vittoria, ASL Cittá di Torino, Italy
Maria Grazia Milia
Affiliation:
Laboratory of Microbiology and Molecular Biology, Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy
Giovanni Di Perri
Affiliation:
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy
Andrea Calcagno
Affiliation:
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy
*
* Address correspondence to: Alessandro Di Stefano, Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy, 00393454852562. ORCID: 0000-0003-0754-6498. (Email: [email protected]) No funding was received for this study. All patients gave their informed consent prior to their inclusion in the study.
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Central nervous system (CNS) may be infected by several agents, resulting in different presentations and outcomes. Analysis of cerebrospinal fluid (CSF) markers could be helpful to differentiate specific conditions and setting an appropriate therapy.

Methods

Patients presenting with signs and symptoms were enrolled if, before receiving a diagnostic lumbar puncture, signed a written informed consent. We analyzed CSF indexes of blood–brain barrier permeability (CSF to serum albumin ratio or CSAR), inflammation (CSF to serum IgG ratio, neopterin), amyloid deposition (1–42 β-amyloid), neuronal damage (Total tau (T-tau), Phosphorylated tau (P-tau), and 14.3.3 protein) and astrocyte damage (S-100β).

Results

Two hundred and eighty-one patients were included: they were mainly affected by herpesvirus encephalitis, enterovirus meningoencephalitis, bacterial meningitis (Neisseria meningitidis and Streptococcus pneumoniae), and infection by other etiological agents or unknown pathogen. Their CSF features were compared with HIV-negative patients and native HIV-positive individuals without CNS involvement. 14.3.3 protein was found in bacterial and HSV infections while T-tau and neopterin were abnormally high in the herpesvirus group. P-tau, instead, was elevated in enterovirus meningitis. S-100β was found to be high in patients with HSV-1 and HSV-2 infections but not in those with Varicella Zoster Virus (VZV). Thirty-day mortality was unexpectedly low (2.7%): patients who died had higher levels of T-tau and, significantly, lower levels of Aβ1–42.

Conclusion

This work demonstrates that CSF biomarkers of neuronal damage or inflammation may vary during CNS infections according to different causative agents. The prognostic value of these biomarkers needs to be assessed in prospective studies.

Keywords

CNS infectionneuromarkersmeningitisneopterintau
Type
Original Research
Information
CNS Spectrums , Volume 25 , Issue 3 , June 2020 , pp. 402 - 408
Copyright
© Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Reiber, H, Peter, JB.Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci. 2001; 184(2): 101–122.Google Scholar
Reiber, H, Reiber, H.Knowledge-base for interpretation of cerebrospinal fluid data patterns. Essentials in neurology and psychiatry. Arq Neuropsiquiatr. 2016; 74(6): 501–512.Google Scholar
Reiber, H.Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases. Diagnostic patterns not to be missed in neurology and psychiatry. Arq Neuropsiquiatr. 2016; 74(4): 337–350.Google Scholar
Tanuma, N, Miyata, R, Nakajima, K, et al.Changes in cerebrospinal fluid biomarkers in human herpesvirus-6-associated acute encephalopathy/febrile seizures. Mediators Inflamm [Internet]. 2014 [cited 2017 Feb 24]. https://www-ncbi-nlm-nih-gov.offcampus.dam.unito.it/pmc/articles/PMC4177780/Google Scholar
Bociąga-Jasik, M, Cieśla, A, Kalinowska-Nowak, A, Skwara, P, Garlicki, A, Mach, T.Role of IL-6 and neopterin in the pathogenesis of herpetic encephalitis. Pharmacol Rep PR. 2011; 63(5): 1203–1209.Google Scholar
Grahn, A, Hagberg, L, Nilsson, S, Blennow, K, Zetterberg, H, Studahl, M.Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections. J Neurol. 2013; 260(7): 1813–1821.Google Scholar
Bonora, S, Zanusso, G, Raiteri, R, et al.Clearance of 14-3-3 protein from cerebrospinal fluid heralds the resolution of bacterial meningitis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2003; 36(11): 1492–1495.Google Scholar
Shimada, T, Fournier, AE, Yamagata, K. Neuroprotective function of 14-3-3 proteins in neurodegeneration. BioMed Res Int [Internet]. 2013 [cited 2017 Feb 7]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865737/Google Scholar
Lu, C-H, Chang, W-N, Chang, H-W, et al.The value of serial cerebrospinal fluid 14-3-3 protein levels in adult community-acquired bacterial meningitis. QJM Mon J Assoc Physicians. 2008; 101(3): 225–230.Google Scholar
Mietelska-Porowska, A, Wasik, U, Goras, M, Filipek, A, Niewiadomska, G.Tau protein modifications and interactions: their role in function and dysfunction. Int J Mol Sci. 2014; 15(3): 4671–4713.Google Scholar
Bloom, GS.Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. 2014; 71(4): 505–508.Google Scholar
Kumar, DKV, Choi, SH, Washicosky, KJ, et al.Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci Transl Med. 2016; 8(340): 340ra72.Google Scholar
Eisenhut, M. Neopterin in diagnosis and monitoring of infectious diseases. J Biomark [Internet] 2013 [cited 2017 Jan 29];. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437389/Google Scholar
Molero-Luis, M, Fernández-Ureña, S, Jordán, I, et al. Cerebrospinal fluid neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes. PLoS ONE [Internet]. 2013 [cited 2017 Jan 29]; 8(12). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867431/Google Scholar
Berdowska, A, Zwirska-Korczala, K.Neopterin measurement in clinical diagnosis. J Clin Pharm Ther. 2001; 26(5): 319–329.Google Scholar