Biomarkers of cerebral injury and inflammation in pediatric tuberculous meningitis
File(s)
Accepted version
Published version
Author(s)
Type
Journal Article
Abstract
Background
Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neuro-specific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome.
Methods
Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analysed for neuromarkers S100B, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and multiple inflammatory markers. Results were compared with 2 control groups; patients with 1) a fatty filum (abnormal filum terminale of the spinal cord), and 2) pulmonary tuberculosis (pTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months.
Results
Data were collected from 44 TBM cases (median age 3.3 [0.3–13.1] years), 11 fatty filum (median age 2.8 [0.8–8] years) and 9 pTB controls (median age 3.7 [1.3–11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated IL-12p40, IP-10 and MCP-1 concentrations, whereas infarcts were associated with elevated TNF-α, MIP-1α, IL-6 and IL-8.
Conclusion
CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM.
Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neuro-specific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome.
Methods
Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analysed for neuromarkers S100B, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and multiple inflammatory markers. Results were compared with 2 control groups; patients with 1) a fatty filum (abnormal filum terminale of the spinal cord), and 2) pulmonary tuberculosis (pTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months.
Results
Data were collected from 44 TBM cases (median age 3.3 [0.3–13.1] years), 11 fatty filum (median age 2.8 [0.8–8] years) and 9 pTB controls (median age 3.7 [1.3–11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated IL-12p40, IP-10 and MCP-1 concentrations, whereas infarcts were associated with elevated TNF-α, MIP-1α, IL-6 and IL-8.
Conclusion
CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM.
Date Issued
2017-06-09
Date Acceptance
2017-06-02
Citation
Clinical Infectious Diseases, 2017, 65 (8), pp.1298-1307
ISSN
1537-6591
Publisher
Oxford University Press (OUP)
Start Page
1298
End Page
1307
Journal / Book Title
Clinical Infectious Diseases
Volume
65
Issue
8
Copyright Statement
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of
America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted
reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: 10.1093/cid/cix540
America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted
reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: 10.1093/cid/cix540
License URL
Sponsor
Wellcome Trust
Grant Number
104803/Z/14/ZR
Subjects
GFAP
NSE
S100B
biomarkers
pediatric tuberculous meningitis
06 Biological Sciences
11 Medical And Health Sciences
Microbiology
Publication Status
Published