Temporal Profile of Soluble TLR4 and its Association with Intracerebral Haemorrhage Expansion

Inflammation contributes to haematoma expansion (HE) and poor prognosis in spontaneous intracerebral haemorrhage (ICH). This study aimed to characterise the temporal profile of soluble Toll-like receptor 4 (sTLR4) during the hyperacute and acute phases of ICH and to evaluate its association with HE. Serum sTLR4 levels were measured at admission, 24 and 72 h from 99 patients with primary hemispheric ICH within 12 h of symptom onset, and at baseline from 39 non-stroke controls using enzyme-linked immunosorbent assay (ELISA). Longitudinal sTLR4 fluctuations were evaluated through linear mixed-effects models. Independent HE prognosticators were identified using multivariable logistic regression, and model performance was assessed via the area under the receiver operating characteristic curve (AUC-ROC). ICH patients exhibited significantly higher baseline sTLR4 levels than controls, which declined over time and were not associated with clinical variables. Notably, patients with HE demonstrated higher admission sTLR4 levels than those without HE (2.50 [95% CI: 1.84-3.16] vs. 1.62 [95% CI: 1.22-2.02] ng/mL, p = 0.027). Furthermore, while the non-HE group showed a rapid decrease within the first 24 h, the HE group maintained elevated levels with a more gradual decline. A multivariable model incorporating baseline ICH volume and sTLR4 levels achieved an AUC of 0.829, with positive and negative predictive values of 70.8% and 90.1%, respectively. These findings suggest that TLR4 may be involved in the pathophysiology of HE, and the combination of baseline ICH volume and sTLR4 levels could serve as a useful tool to stratify patients into low- and high-risk groups for HE.