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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
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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: alessandro.distefano@edu.unito.it) No funding was received for this study. All patients gave their informed consent prior to their inclusion in the study.
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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

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