Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis

Abstract

Introduction Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compared the concentrations of cerebrospinal fluid (CSF) and serum proteins between children who had TBM-related stroke and children with TBM without stroke. Methods We collected CSF and serum from 47 children consecutively admitted to the Tygerberg Academic Hospital in Cape Town, South Africa between November 2016, and November 2017, on suspicion of having TBM. A multiplex platform was used to measure the concentrations of 69 host proteins in CSF and serum from all study participants. Results After classification of study participants, 23 (48.9%) out of the 47 study participants were diagnosed with TBM, of which 14 (60.9%) demonstrated radiological arterial ischemic infarction. The levels of lipocalin-2, sRAGE, IP-10/ CXCL10, sVCAM-1, MMP-1, and PDGF-AA in CSF samples and the levels of D-dimer, ADAMTS13, SAA, ferritin, MCP-1/ CCL2, GDF-15 and IL-13 in serum samples were statistically different between children who had TBM-related stroke and children with TBM without stroke. After correcting for multiple testing, only the levels of sVCAM-1, MMP-1, sRAGE, and IP-10/ CXCL10 in CSF were statistically different between the two groups. CSF and serum protein biosignatures indicated stroke in children diagnosed with TBM with up to 100% sensitivity and 88.9% specificity. Conclusion Serum and CSF proteins may serve as biomarkers for identifying individuals with stroke amongst children diagnosed with TBM at admission and may guide us to understand the biology of stroke in TBM. This was a pilot study, and thus further investigations in larger studies are needed.

Analysis of Cases with Cerebrospinal Fluid Characteristics Similar to Tuberculous Meningitis

“…This is crucial for the clinical recognition of TBM and cryptococcal infection [6]. Again, early cerebrospinal fluid changes are highly suggestive of TBM, such as (i) elevated cell counts (100-500/μL), mainly lymphocytes and possibly neutrophils in the early stages of the disease; (ii) elevated protein levels (up to 1000-5000 mg/L); and (iii) decreased glucose levels (<2.5 mol/L) or cerebrospinal fluid/plasma ratios < 0:5 [7][8][9]. In the present study, the early cerebrospinal fluid leukocyte count, protein level, and glucose level of all enrolled patients were similar to the cerebrospinal fluid changes in TBM.…”

Prognostic Identifier of Cerebrovascular Complications in Tuberculous Meningitis: Meta-Analysis

“…High serum and CSF IL-4 and IL-1β levels are correlated with the presence of an MRI brain infarction [34]. In addition, increased lumbar and ventricular CSF TNF-α, macrophage in ammatory protein 1α, IL-6, IL-8, and markers of brain injury were also found to be associated with infarction in patients with TBM [35,36].…”

Neutrophil-Mediated Immunopathology and Matrix Metalloproteinases in Central Nervous System – Tuberculosis

“…The upregulated inflammatory cytokines TNF-α, MIP-1α, IL-6, IL-8, IL-4 and IL-1β concentrations in CSF samples were correlated with the presence of infarcts in TBM patients ( 204 , 205 ). In another study, the concentrations of lipocalin-2, soluble receptor for advanced glycation end products (sRAGE) and CXCL10 were significantly higher in the CSF of children with TBM-related stroke compared to TBM without stroke ( 206 ). Moreover, Schoeman et al.…”