Brain Imaging and Whole Blood Targeted Transcriptomic Analyses to Characterize Cerebral Infarctions in Children With Tuberculous Meningitis.
Huynh J., Pretorius PM., Jan W., Kachramanoglou C., Le NHT., Ngoc VL., Hoang HT., Tran NTH., Pham TN., Dang Do TA., Vu DTM., Tram TTB., Vinh DD., Trinh TH., Qui ND., Dang MHT., Frangou E., Santana S., Muller C., Anderson ST., Gibb DM., Nguyen NTH., Thuong NTT., Thwaites G.
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.