Chemical Angioplasty with Nitroglycerin for Vasospasm after Subarachnoid Hemorrhage: Case Series and Review

Introduction Vasospasm is a common and potentially devastating complication in patients with subarachnoid hemorrhage, causing high morbidity and mortality. There is no effective and consistent way to prevent or treat cerebral vasospasm capable of altering the morbidity and mortality of this complication. Animal and human studies have attempted to show improvement in aneurysmal vasospasm. Some sought their prevention; others, the treatment of already installed vasospasm. Some achieved only angiographic improvement without clinical correlation, others achieved both, but with ephemeral duration or at the expense of very harmful associated effects. Endovascular techniques allow immediate and aggressive treatment of cerebral vasospasm and include methods such as mechanical and chemical angioplasty. These methods have risks and benefits. Objectives To analyze the results of chemical angioplasty using nitroglycerin (GTN). In addition, to perform a comprehensive review and analysis of aneurysmal vasospasm. Methods We describe our series of 77 patients treated for 8 years with angioplasty for vasospasm, either mechanical (with balloon), chemical (with GTN) or both. Results Eleven patients received only balloon; 37 received only GTN; 29 received both. Forty-four patients (70.1%) evolved with delayed cerebral ischemia and 19 died (mortality of 24.7%). Two deaths were causally related to the rupture of the vessel by the balloon. The only predictors of poor outcome were the need for external ventricular drainage in the first hours of admission, and isolated mechanical angioplasty. Conclusions Balloon angioplasty has excellent results, but it is restricted to proximal vessels and is not without complications. Chemical angioplasty using nitroglycerin has reasonable but short-lived results and further research is needed about it. It is restricted to vasospasm angioplasties only in hospitals, like ours, where better and more potent vasodilator agents are not available.

DCI after Aneurysmal Subarachnoid Hemorrhage Is Related to the Expression of MFG-E8

Objective. To explore the predictive value of milk fat globule epidermal growth factor 8 (MFG-E8) in the occurrence of delayed cerebral ischemia (DCI) after an aneurysmal subarachnoid hemorrhage (aSAH). Methods. We recruited 32 patients with aSAH as the case group and 24 patients with unruptured aneurysms as the control group. Serum MFG-E8 levels were measured by western blot and enzyme-linked immunosorbent assay. We analyzed the relationship between MFG-E8 levels and the risk of DCI. Results. The levels of serum MFG-E8 in the case group ( mean = 11160.9 pg/mL) were significantly higher than those in the control group ( mean = 3081.0 pg/mL, p < 0.001 ). MFG-E8 levels highly correlated with the World Federation of Neurosurgical Societies (WFNS) and modified Fisher scores ( r = − 0.691 and − 0.767 , respectively, p < 0.001 ). In addition, MFG-E8 levels in patients with DCI ( 5882.7 ± 3162.4 pg/mL) were notably higher than those in patients without DCI ( 15818.2 ± 3771.6 pg/mL, p < 0.001 ). A receiver operating characteristic curve showed that the occurrence of DCI could effectively be predicted by MFG-E8 (area under the curve = 0.976 , 95 % CI = 0.850 – 1.000 ). Kaplan–Meier survival analysis showed a remarkable decrease in the incidence of DCI in case group individuals with high levels of MFG-E8 (≥11160.9 pg/mL, p < 0.001 ). Conclusion. MFG-E8 may be a useful predictive marker for DCI after an aSAH and could be a promising surrogate end point.

Higher Cystatin C Level Increase the Risk of Delayed Cerebral Ischemia after Endovascular Treatment of Aneurysmal Subarachnoid Hemorrhage: A Case-Control Study.

Cystatin C (CysC) has been found to be associated with hemorrhagic and ischemic stroke in many studies. However, the association between CysC level and the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage has been reported rarely. Our study was proposed to explore this association. Consecutive patients from June 2015 to February 2021 in this single-center retrospective study were selected. Univariate and multivariate analyses were used to identify potential prognostic risk factors for delayed cerebral ischemia, and the stability of the association was demonstrated by several statistical methods, such as subgroup analysis, interaction testing, generalized linear models, and propensity score matching. A total of 424 patients were included in the analysis. Cystatin C was independently associated with delayed cerebral ischemia. The independent effects of CysC on delayed cerebral ischemia were shown in generalized linear models with a logit link, and the results were relatively stable in crude, partial, and full models with ORs (95% CIs) for delayed cerebral ischemia. Subgroup analysis showed no significant subgroup differences in the effect of CysC on delayed cerebral ischemia. There was also no interaction effect between CysC and other confounders. Patients in the high CysC group had a higher risk of delayed cerebral ischemia than those in the low CysC group before and after propensity score matching. CysC level could be an independent predictor for the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage.

An Update on Antioxidative Stress Therapy Research for Early Brain Injury After Subarachnoid Hemorrhage

The main reasons for disability and death in aneurysmal subarachnoid hemorrhage (aSAH) may be early brain injury (EBI) and delayed cerebral ischemia (DCI). Despite studies reporting and progressing when DCI is well-treated clinically, the prognosis is not well-improved. According to the present situation, we regard EBI as the main target of future studies, and one of the key phenotype-oxidative stresses may be called for attention in EBI after laboratory subarachnoid hemorrhage (SAH). We summarized the research progress and updated the literature that has been published about the relationship between experimental and clinical SAH-induced EBI and oxidative stress (OS) in PubMed from January 2016 to June 2021. Many signaling pathways are related to the mechanism of OS in EBI after SAH. Several antioxidative stress drugs were studied and showed a protective response against EBI after SAH. The systematical study of antioxidative stress in EBI after laboratory and clinical SAH may supply us with new therapies about SAH.

ANGPT1 methylation and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients

Background Delayed cerebral ischemia (DCI) is a common secondary complication and an important cause of disability and mortality among patients who survive aneurysmal subarachnoid hemorrhage (aSAH). Knowledge on DCI pathogenesis, risk factors, and biomarkers are essential for early detection and improved prognosis. To investigate the role of DNA methylation in DCI risk, we conducted an epigenome-wide association study (EWAS) in 68 patients followed up to 1 year after the initial aneurysm rupture. Blood samples were collected within 48 h post hemorrhage and used for DNA methylation profiling at ~ 450k CpG sites. A separate cohort of 175 patients was sequenced for the top CpG sites from the discovery analysis for a replication of the EWAS findings. Results EWAS did not identify any epigenome-wide significant CpGs. The top signal, cg18031596, was annotated to ANGPT1, a gene with critical functions in angiogenesis after vascular injury. Post hoc power calculations indicated a well-powered discovery analysis for cg18031596. Analysis of the replication cohort showed that four out of the five CpG sites sequenced at the ANGPT1 locus passed a Bonferroni-adjusted significance threshold. In a pooled analysis of the entire sample, three out of five yielded a significant p-value, and the top association signal (p-value = 0.004) was seen for a CpG that was not originally measured in the discovery EWAS. However, four ANGPT1 CpG sites had an opposite effect direction in the replication analysis compared to the discovery EWAS, marking a failure of replication. We carefully examined this observed flip in directions and propose several possible explanations in addition to that it was a random chance that ANGPT1 ranked at the top in the discovery EWAS. Conclusions We failed to demonstrate a significant and consistent effect of ANGPT1 methylation in DCI risk in two cohorts. Though the replication attempt to weaken the overall support of this gene, given its relevant function and top rank of significance in the EWAS, our results call for future studies of larger aSAH cohorts to determine its relevance for the occurrence of DCI.