Background: Hyperhomocysteinemia (HHcy) is a risk factor for thromboembolic disease. Defects in one-carbon metabolism (1-CM)-related genes, such as methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1), can cause HHcy and may also affect the efficacy of folic acid therapy. The details of mechanisms are yet to be further investigated.Method: We described a Chinese family with hereditary HHcy. The proband suffered from severe thromboembolic disease and experienced failure of folic acid therapy. Two sons of the proband were also diagnosed with HHcy but were sensitive to folic acid therapy. Whole-exome sequencing (WES) was conducted to evaluate the genetic lesion of this family.Results: Compound heterozygous variants (a common polymorphism, p. A222V, and a novel variant, p. C631*fs*1) of the MTHFR gene and a homozygous missense variant (p. K134R) of the MTHFD1 gene were identified in the proband. The two sons, with successful intervention, only harbored the homozygous p. A222V variant of the MTHFR gene.Conclusion: The clinical manifestations and genetic research synergistically confirmed the diagnosis of HHcy and clarified the failure of folic acid therapy in the proband caused by doubly bi-allelic variants of the MTHFR and MTHFD1 genes. Our study increased our understanding of the molecular basis of 1-CM-related gene defects on folic acid therapy in HHcy.

Background: It is essential to understand the factors that influence patient outcomes in stroke research. The infarct core growth rate (ICGR) is emerging as a potentially valuable marker, but its relationship with patient outcomes, especially concerning the onset-to-recanalization time (ORT), requires further clarification. This study investigates the impact of ICGR on 90-day (90d) outcomes in acute ischemic stroke patients and explores whether stratifying ICGR analysis based on ORT provides more detailed prognostic insights.Methods: This study retrospectively analyzed patients with acute ischemic stroke with anterior circulation large vessel occlusion (AIS-ACLVO) who underwent endovascular treatment (EVT) between January 2021 and December 2023. Their clinical characteristics, baseline and imaging data were recorded upon admission. Clinical outcomes were evaluated using the modified Rankin Scale (mRS) at 90 days post-procedure. The least absolute shrinkage and selection operator (LASSO) regression was employed for data screening. Multivariable logistic regression analysis was performed to explore the relationship between ICGR and 90-day (90d) clinical outcome. Additionally, a stratified analysis based on ORT was conducted to compare the diagnostic performance of ICGR and infarct core volume (ICV) at different time points.Results: A total of 153 patients were included in the analysis. Univariate and Lasso regression analyses showed that the group with unfavorable outcomes had statistically significant differences in ICGR, age, history of atrial fibrillation, history of drinking, admission blood glucose level, Alberta Stroke Program Early CT Score (ASPECTS), and National Institutes of Health Stroke Scale (NIHSS) score compared to the favorable outcome group (all p < 0.05). Furthermore, multivariate logistic regression analysis indicated that ICGR was independently associated with clinical outcome in AIS-ACLVO patients [Odds Ratio (OR) 1.101, 95% confidence interval (CI) 1.029–1.178; p = 0.005]. When stratified by median ORT, the ICGR remained a strong predictor of outcome within 8 h (OR 1.188, 95% CI 1.048–1.347; p = 0.007), and proved to be a better predictor than ICV [area under the Receiver Operating Characteristic (AUROC) curve, 0.816 vs. 0.750, p = 0.024].Conclusion: Our research indicates that the ICGR correlates with 90d clinical outcomes in AIS-ACLVO patients: a faster rate is associated with poorer outcomes. Within 8 h of ORT, the ICGR serves as a better predictor of 90d outcome than ICV.

Background and purpose: Mechanical thrombectomy advances enable detection of thrombus composition changes post-intravenous thrombolysis, but evidence remains limited. This study retrospectively analyzed thrombi obtained from mechanical thrombectomy in patients with acute ischemic stroke to explore the impact of intravenous thrombolysis (IVT) on the composition of thrombi in patients with different TOAST classifications and the association between changes in thrombus components and clinical outcome data. Materials and methods: Thrombus samples from 141 patients undergoing mechanical thrombectomy ( n = 60) or bridging therapy ( n = 81) at two hospitals between December 2020 and January 2024 were included. Baseline data and outcome data were collected. Components were analyzed via HE staining and immunohistochemistry for CD61 and FGB, quantifying area percentages of red blood cell (RBC), white blood cell (WBC), platelet-fibrin complexes (PLT + FIB), platelet (PLT), and fibrin (FIB). Thrombus components were compared between the mechanical thrombectomy and bridging therapy groups according to TOAST subtypes, and a combined analysis was conducted with clinical prognosis and surgical conditions. Results: No significant baseline differences ( p > 0.05). Significant component differences between mechanical thrombectomy and bridging therapy across subtypes: in large artery atherosclerotic (LAA), FIB higher in mechanical thrombectomy ( p = 0.001); in cardioembolic (CE), PLT and FIB higher in mechanical thrombectomy ( p = 0.003, p < 0.001). Subtype comparisons showed differences: LAA vs. CE in RBC, PLT + FIB, PLT, FIB ( p < 0.05); LAA vs. stroke of undetermined source (SUE) in PLT and FIB ( p < 0.05); CE vs. SUE in FIB ( p < 0.05). Conclusion: This study quantified the thrombus components of different etiologies and found that IVT could reduce the FIB content in thrombi of large artery occlusion cerebral infarction, especially in the LAA type. The platelet content in the LAA type was higher than that in the CE and the SUE types. The FIB level in the SUE type was higher than that in the CE type. FIB was not only present in the PLT area but also in the RBC area. IVT may improve thrombectomy success by disrupting thrombus structure, but it can increase fragment embolization and prolong procedure time.