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Updated: Sep 13, 2025
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Published on: October 28, 2022
Brain Imaging and Whole Blood Targeted Transcriptomic Analyses to Characterize Cerebral Infarctions in Children With
Julie Huynh1,2, Pieter M Pretorius3, Wajanat Jan4
1Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.
Abstract:
We characterized cerebral infarction in children with tuberculous meningitis and explored its relationship with systemic inflammatory mediators using targeted transcriptomic analysis. Children with tuberculous meningitis had baseline magnetic resonance imaging scans and whole blood RNA sequencing for matrix metalloproteinases (MMP-8, MMP-9, TIMP-1), cytokines (IL-10, IL-1β, TNF-α, IFN-γ), and growth factors (VEGF). Overall 22 (73%) children had mild disease and 19 (63%) had cerebral infarctions, which were commonly acute (n = 9, 47%), multiple (n = 14, 74%), and bilateral (n = 12, 63%), occurring in cerebral hemispheres (n = 12, 59%), basal ganglia (n = 10, 53%), and thalamus (n = 5, 26%). Children with infarctions had significantly higher cerebrospinal fluid protein, lower cerebrospinal fluid glucose, and higher systemic MMP-8 expression.
Insights
Cerebral infarctions are common in pediatric tuberculous meningitis (TBM). Higher systemic matrix metalloproteinase-8 (MMP-8) expression correlated with these brain injuries in children with TBM.
Area of Science:
- Neurology
- Pediatrics
- Immunology
Background:
- Tuberculous meningitis (TBM) is a severe infection affecting children.
- Cerebral infarctions are a known complication of TBM, but their relationship with inflammatory markers requires further investigation.
Purpose of the Study:
- To characterize cerebral infarctions in children with TBM.
- To explore the association between cerebral infarctions and systemic inflammatory mediators.
Main Methods:
- Magnetic Resonance Imaging (MRI) for infarction assessment.
- Targeted transcriptomic analysis of whole blood for inflammatory markers including matrix metalloproteinases (MMP-8, MMP-9, TIMP-1), cytokines (IL-10, IL-1β, TNF-α, IFN-γ), and growth factors (VEGF).
Main Results:
- Cerebral infarctions were present in 63% of children with TBM.
- Infarctions were frequently acute, multiple, and bilateral, affecting cerebral hemispheres, basal ganglia, and thalamus.
- Children with infarctions showed higher cerebrospinal fluid (CSF) protein, lower CSF glucose, and elevated systemic MMP-8 expression.
Conclusions:
- Cerebral infarctions are a significant complication in pediatric TBM.
- Systemic MMP-8 expression may be a potential biomarker associated with cerebral infarctions in TBM.
- Further research is warranted to understand the role of MMP-8 in TBM pathogenesis.
