[Cerebrolysin with reperfusion therapy in ischemic stroke: a prospective analysis of multimodal brain imaging data from the CEREHETIS trial].

Abstract

Objective: To evaluate the effects of Cerebrolysin on brain microstructural integrity and blood-brain barrier (BBB) permeability, as well as their longitudinal changes, using diffusion tensor imaging (DTI) and perfusion computed tomography (PCT) in patients with acute ischemic stroke (AIS).

Material and methods: This analysis included patients from the multimodal brain imaging subgroup of the prospective CEREHETIS trial (ISRCTN87656744) with AIS in the middle cerebral artery territory. The intervention group (IG, n=16) received Cerebrolysin in combination with intravenous thrombolysis (IVT) and standard care, while the control group (CG, n=17) received IVT and standard care alone. Brain imaging was performed at 24 hours and on day 14 post-IVT. DTI metrics included axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD; 10^-6 mm²/s), and fractional anisotropy (FA; ·10^-4) assessed within the infarct core and contralateral region. BBB permeability (PS; mL/100 g/min) was measured on day 14 using PCT. Infarct volume (mL) was determined by diffusion-weighted imaging at 24 hours and by non-contrast CT on day 14. Mixed-effects linear regression models accounting for repeated measures were used to evaluate treatment effects over time, incorporating clinical and imaging predictors, timepoints, and interaction terms.

Results: At 24 hours, no significant differences in imaging parameters were observed between groups. By day 14, the IG exhibited significantly higher values of AD (predicted marginal contrast: 259.05; 95% CI 142.19-375.91; p<0.001), RD (209.89; 95% CI 106.91-312.87; p<0.001), and FA (185.13; 95% CI 22.88-347.37; p=0.021), alongside lower PS values (-1.41; 95% CI -1.69 to -1.13; p<0.001) and smaller infarct volume (-6.98; 95% CI -10.13 to -3.82; p<0.001). The severity of ischemic injury and functional outcomes were largely influenced by the baseline condition of brain tissue and BBB integrity.

Conclusion: Cerebrolysin treatment was associated with favorable changes in quantitative imaging biomarkers, indicating better preservation of brain microstructure, stabilization of BBB permeability, and a reduction in infarct volume in patients with AIS. These findings support the potential cytoprotective effects of Cerebrolysin and highlight the utility of DTI and PCT for evaluating therapeutic efficacy and guiding individualized neuroprotective strategies.