Epithelial–mesenchymal transition related genes in unruptured aneurysms identified through weighted gene coexpression network analysis

Intracranial aneurysm (IA) can cause fatal subarachnoid hemorrhage (SAH) after rupture, and identifying patients with unruptured IAs is essential for reducing SAH fatalities. The epithelial–mesenchymal transition (EMT) may be vital to IA progression. Here, identified key EMT-related genes in aneurysms and their pathogenic mechanisms via bioinformatic analysis. The GSE13353, GSE75436, and GSE54083 datasets from Gene Expression Omnibus were analyzed with limma to identify differentially expressed genes (DEGs) among unruptured aneurysms, ruptured aneurysms, and healthy samples. The results revealed that three EMT-related DEGs (ADIPOQ, WNT11, and CCL21) were shared among all groups. Coexpression modules and hub genes were identified via weighted gene co-expression network analysis, revealing two significant modules (red and green) and 14 EMT-related genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that cytokine interactions were closely related. Gene set enrichment analysis revealed that unruptured aneurysms were enriched for the terms “inflammatory response” and “vascular endothelial growth”. Protein–protein interaction analysis identified seven key genes, which were evaluated with the GSE54083 dataset to determine their sensitivity and specificity. In the external validation set, we verified the differential expression of seven genes in unruptured aneurysms and normal samples. Together, these findings indicate that FN1, and SPARC may help distinguish normal patients from patients with asymptomatic IAs.

Spontaneous Disappearance of Unruptured Intracranial Aneurysm: A Case Report

Spontaneous resolution or thrombosis of giant or ruptured intracranial aneurysms is occasionally reported. However, spontaneous resolution of unruptured aneurysms without any intervention is extremely rare. Recently, we encountered a case of spontaneous resolution of a small unruptured aneurysm of the anterior communicating artery. We describe this rare case and discuss the mechanism of resolution with a review of the related literature.

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.

Safety and Efficacy of Endovascular Embolization of Ruptured Intracranial Aneurysms within 72 hours of Subarachnoid Hemorrhage

Purpose The purpose of the study was to investigate the safety and efficacy of endovascular embolization of ruptured intracranial aneurysms within 72 hours of subarachnoid hemorrhage (SAH). Materials and methods Patients with intracranial aneurysms treated with embolization were divided into group A (n = 277), patients with ruptured aneurysms treated within 72 hours of SAH; group B (n = 138), patients with ruptured aneurysms treated beyond 72 hours; and group C (n = 93), patients with unruptured aneurysms. Results Embolization was successful in all but four patients (99.2%). The periprocedural complication rate was 36.2% in group B, significantly (p < 0.05) greater than that in group A (24.5%) or group C (11.8%). The rebleeding rate was 9.7% (6/62 patients) in groups A and B after embolization and only 0.3% (1/346 patients) in aneurysms with total or subtotal occlusion. Of these three groups of patients, 69.7% in group A, 58.7% in group B, and 76.3% in group C achieved Glasgow Outcome Scale (GOS) score of 5 or modified Rankin Scale (mRS) score of 0– to 1 at discharge. A significant difference (p < 0.05) existed in the clinical outcome between the three groups. The percentages of patients without deficits (GOS 5 or mRS 0–1) and slight disability (mRS 2) were 80.2% in group A, 81.2% in group B, and 96.7% in group C. The mortality rate was 4.3% (12/277 patients) in group A and 7.2% (10/138 patients) in group B with no significant (p = 0.21) difference. Follow-up was performed at 3 to 54 months (mean 23.2), and the recanalization rate was 28.6% (32/112 patients) in group A, 22.4% (11/49 patients) in group B, and 28.6% (16/56 patients) in group C, with no significant differences (p = 0.15). Hydrocephalus occurred in 30.5% (39/128 patients) in group B, which was significantly (p < 0.01) greater than that in group A (9.4%) or group C (2.2%). Conclusion Early embolization of ruptured cerebral aneurysms within 72 hours of rupture is safe and effective and can significantly decrease periprocedural complications compared with management beyond 72 hours. Timely management of cisternal and ventricular blood can reduce hydrocephalus incidence and improve prognosis.

Intraoperative motor and somatosensory evoked potential monitoring during surgical clipping of ruptured and unruptured intracranial aneurysms: a comparative study

OBJECTIVE The current study investigated the correlation between intraoperative motor evoked potential (MEP) and somatosensory evoked potential (SSEP) monitoring and both short-term and long-term motor outcomes in aneurysm patients treated with surgical clipping. Moreover, the authors provide a relatively optimal neurophysiological predictor of postoperative motor deficits (PMDs) in patients with ruptured and unruptured aneurysms. METHODS A total of 1017 patients (216 with ruptured aneurysms and 801 with unruptured aneurysms) were included. Patient demographic characteristics, clinical features, intraoperative monitoring data, and follow-up data were retrospectively reviewed. The efficacy of using changes in MEP/SSEP to predict PMDs was assessed using binary logistic regression analysis. Subsequently, receiver operating characteristic curve analysis was performed to determine the optimal critical value for duration of MEP/SSEP deterioration. RESULTS Both intraoperative MEP and SSEP monitoring were significantly effective for predicting short-term (p < 0.001 for both) and long-term (p < 0.001 for both) PMDs in aneurysm patients. The critical values for predicting short-term PMDs were amplitude decrease rates of 57.30% for MEP (p < 0.001 and area under the curve [AUC] 0.732) and 64.10% for SSEP (p < 0.001 and AUC 0.653). In patients with an unruptured aneurysm, the optimal critical values for predicting short-term PMDs were durations of deterioration of 17 minutes for MEP (p < 0.001 and AUC 0.768) and 21 minutes for SSEP (p < 0.001 and AUC 0.843). In patients with a ruptured aneurysm, the optimal critical values for predicting short-term PMDs were durations of deterioration of 12.5 minutes for MEP (p = 0.028 and AUC 0.706) and 11 minutes for SSEP (p = 0.043 and AUC 0.813). CONCLUSIONS The authors found that both intraoperative MEP and SSEP monitoring are useful for predicting short-term and long-term PMDs in patients with unruptured and ruptured aneurysms. The optimal intraoperative neuromonitoring method for predicting PMDs varies depending on whether the aneurysm has ruptured or not.

Abstract 1122‐000145: Impact of Age on Outcomes Following Endovascular vs Clipping of Ruptured and Unruptured Cerebral Aneurysms

Introduction : Age is an important determinant of outcome in patients with unruptured or ruptured cerebral aneurysms. Advancements in endovascular therapies have significantly impacted patient selection and treatment of patients with cerebral aneurysm. Recent release of the National claims data for 2017–2018 provides the opportunity to explore novel population‐level outcomes following clipping vs endovascular treatment of ruptured and unruptured cerebral aneurysms in different age groups. Methods : Analysis of US National Inpatient Sample of hospitalizations with aneurysmal subarachnoid hemorrhage (aSAH) or unruptured aneurysms treated with clipping or endovascular therapy from January 1, 2017 to December 31, 2018. Pre‐defined age strata included: younger than 50 years; 50–64 years; 65–79 years; and 80 years or older. Primary outcomes included in‐hospital mortality and favorable outcome defined as discharge to home. Results : Overall, 34,955 hospitalizations with unruptured aneurysm treatment, (26,695 endovascular and 8,260 surgical clipping), and 17,525 hospitalizations with aSAH were identified in the study period. In unruptured aneurysm group, endovascular therapy was associated with significantly higher favorable outcome across all age groups, and lower mortality in those 65 years or older (all P<0.001) when compared to clipping. Median hospital length‐of‐stay was 1 day (IQR 1–4) in endovascular vs 4 days (IQR 3–8) in clipping group (P<0.001). In aSAH group, endovascular therapy was associated with higher favorable outcome in 50–80 years age groups when compared to clipping, with no significant differences for in‐hospital mortality outcome (Table). Significantly more favorable outcomes were achieved with coiling vs clipping in those aged 65 or above with unruptured aneurysms. Conclusions : In 2017–2018 in US, unruptured aneurysm patients treated with endovascular therapy had significantly lower morbidity and mortality compared to those treated with surgical clipping, and differences were more pronounced with age. Similar but less strong association was observed in patients with aSAH.

Abstract 1122‐000056: Trends in the Endovascular Treatment of Intracranial Aneurysms in a Single Institution During 10 Years

Introduction : Endovascular treatment of intracranial aneurysms has increased compared to microsurgery since the creation of the Guglielmi Detachable Coils (GDC), and is the treatment of choice in several centers worldwide. Our study aimed to analyze the trends over time of number of patients, number of aneurysms, rupture status, location, size and endovascular technique employed in a retrospective cohort of consecutive intracranial aneurysms treated during a 10‐year period. Methods : Data extracted from clinical records, surgical reports, angiographies and CT scans of 765 consecutive patients who underwent endovascular treatment of 845 intracranial aneurysms at our institution between January 2010 and December 2020 was carried out. The Mann‐Kendal test was used to assess time trends. The moving average technique was also employed, using one lagged observation, the current observation and one forward observation in order to create smoother curves. The statistical software Stata v14.0 (StataCorp, College Station, TX, USA) was used. Results : We evaluated 765 patients who underwent 845 endovascular treatments of intracranial aneurysms. Women represented 81% of the cohort. Mean age was 53.9 ± 14.6 years. We identified a significant increase in the number of patients (p = 0.016; p for moving average = 0.005) and in the number of aneurysms over time (p = 0.003; p for moving average = 0.003). For ruptured aneurysms, we did not find changes in the trends over time (p = 0.117; p for moving average = 0.1), whereas in the case of unruptured aneurysms, we identified a significant increase in their treatment (p = 0.029; p for moving average = 0.001). Posterior communicating (p = 0.042: p for moving average = 0.002), paraclinoid (p = 0.06; p for moving average = 0.019) and posterior fossa aneurysms (p = 0.813; p for moving average = 0.028) increased their frequency of treatment over time. Anterior communicating (p = 0.235; p for moving average = 0.21), middle cerebral artery (p = 0.431; p for moving average = 0.347) and internal carotid artery aneurysms (p = 1; p for moving average = 0.754) did not show differences over time. We did not identify changes over time in large (p = 0.31; p for moving average = 0.213), as well as width (p = 0.35; p for moving average = 0.876) and neck diameter (p = 1; p for moving average = 0.815). Balloon‐assisted coiling (p = 0.01; p for moving average = 0.003), flow diverters (p = 0.016; p for moving average < 0.001) and stent‐assisted coiling (p = 0.531; p for moving average = 0.014) showed a positive trend over time. Simple coiling (p = 0.75; p for moving average = 0.184) did not show significant variations over time. Conclusions : We identified a positive trend in the endovascular treatment of unruptured aneurysms, as well as posterior communicating artery, paraclinoid and posterior fossa aneurysms. Assisted‐coiling techniques and flow diverters also showed a positive trend over time. These results are in accordance with the increasing trends in endovascular treatment of intracranial aneurysms worldwide.

Abstract 1122‐000195: Endovascular Coiling Versus Neurosurgical Clipping for Treatment of Ruptured and Unruptured Intracranial Aneurysms During Pregnancy

Introduction : Management of intracranial aneurysms during pregnancy is challenging. The hemodynamic changes during pregnancy increase the risk of intracranial aneurysm rupture. Further, the selection of an appropriate surgical strategy requires a careful review of the potential risks to the mother and fetus. Yet, there is limited data to guide the treatment decisions in this patient population. In this study, we aimed to compare the safety profiles of endovascular coiling (EC) and neurosurgical clipping (NC) in this patient population. Methods : Pregnancy‐related hospitalizations with age≥18 years undergoing surgical intervention for intracranial aneurysms were identified from the Nationwide Readmissions Database 2016–2018. Hospitalizations with diagnoses of arteriovenous malformation, cerebral arteritis, and traumatic SAH were excluded. Logistic regression analysis was used to compare outcomes between EC and NC. Results : There were 11829044 pregnancy‐related hospitalizations, of which 348 met the study inclusion criteria (mean±SD age: 31.8±5.9). Among 168 patients treated for ruptured aneurysms, 115 (68.5%) underwent EC and 53 (31.5%) underwent NC. Whereas among 180 patients treated for unruptured aneurysms, 140 (77.8%) underwent EC and 40 (22.2%) underwent NC. There were no statistically significant differences in the demographics, clinical presentation, and hospital‐level characteristics between patients undergoing EC versus NC for either ruptured or unruptured aneurysm groups. Among patients with ruptured aneurysms, 11.9% patients had perioperative ischemic stroke, 22.6% patients required mechanical ventilation for >24 hours, 6.5% patients underwent tracheostomy, 6.5% patients had acute kidney injury, 20.2% patients had infectious complications, 4.2% patients underwent gastrostomy tube placement, 30.0% patients had discharge disposition other than to home, 10.1% patients had in‐hospital mortality, and 4.8% patients had non‐elective readmission within 30 days of discharge. These outcomes were comparable between patients with EC and NC, except patients undergoing EC were less likely to develop ischemic stroke [odds ratio (OR): 0.21, 95% confidence interval (CI): 0.05‐0.98] (Figure 1A). None of the 30‐day readmissions were due to procedural complications and a majority (75%) of them were due to pregnancy‐related conditions. Among patients with unruptured aneurysms, 5.6% patients had perioperative ischemic stroke, 5.0% patients required mechanical ventilation for >24 hours, 6.1% patients had infectious complications, 11.1% patients had discharge disposition other than to home, 0.01% patient had in‐hospital mortality, and 0.01% patient had non‐elective readmission within 30 days of discharge. There were no significant differences in these outcomes or in the average length of hospital stay among patients undergoing EC versus NC for unruptured aneurysms (Figure 1B). Conclusions : Surgical treatment of intracranial aneurysms during pregnancy is safe with a relatively low rate of early complications. While a majority of patients undergo EC, we found that the safety profiles of NC and EC are largely comparable. Future large studies are needed to further evaluate the advantages and disadvantages of these procedures in detail in this patient population.

Aneurysm risk metrics and hemodynamics are associated with greater vessel wall enhancement in intracranial aneurysms

Vessel wall enhancement (VWE) in contrast-enhanced magnetic resonance imaging (MRI) is a potential biomarker for intracranial aneurysm (IA) risk stratification. In this study, we investigated the relationship between VWE features, risk metrics, morphology and hemodynamics in 41 unruptured aneurysms. We reconstructed the IA geometries from MR angiography and mapped pituitary stalk-normalized MRI intensity on the aneurysm surface using an in-house tool. For each case, we calculated the maximum intensity (CR stalk ) and IA risk (via size and the rupture resemblance score (RRS)). We performed correlation analysis to assess relationships between CR stalk and IA risk metrics (size and RRS), as well as each parameter encompassed in RRS, i.e. aneurysmal size ratio (SR), normalized wall shear stress (WSS) and oscillatory shear index. We found that CR stalk had a strong correlation (Pearson correlation coefficient, PCC = 0.630) with size and a moderate correlation (PCC = 0.472) with RRS, indicating an association between VWE and IA risk. Furthermore, CR stalk had a weak negative correlation with normalized WSS (PCC = −0.320) and a weak positive correlation with SR (PCC = 0.390). Local voxel-based analysis showed only a weak negative correlation between normalized WSS and contrast-enhanced MRI signal intensity (PCC = −0.240), suggesting that if low-normalized WSS induces enhancement-associated pathobiology, the effect is not localized.

Predictors of incomplete aneurysm occlusion after treatment with the Pipeline Embolization Device: PREMIER trial 1 year analysis

BackgroundFlow diverters have revolutionized the treatment of intracranial aneurysms. Nevertheless, some aneurysms fail to occlude with flow diversion. The Prospective Study on Embolization of Intracranial Aneurysms with the Pipeline Device (PREMIER) was a prospective, multicenter and single-arm trial of small and medium wide-necked unruptured aneurysms. In the current study, we evaluate the predictors of treatment failure in the PREMIER cohort.MethodsWe analyzed PREMIER patients who had incomplete occlusion (Raymond-Roy >1) at 1 year angiographic follow-up and compared them with those who achieved Raymond-Roy 1, aiming to identify predictors of treatment failure.Results25 aneurysms demonstrated incomplete occlusion at 1 year. There was a median reduction of 0.9 mm (IQR 0.41–2.43) in maximum diameter between pre-procedure and 1 year measurements, with no aneurysmal hemorrhage. Patients with incomplete occlusion were significantly older than those with complete occlusion (p=0.011). Smoking (p=0.045) and C6 segment location (p=0.005) were significantly associated with complete occlusion, while location at V4 (p=0.01) and C7 (p=0.007) and involvement of a side branch (p<0.001) were significantly associated with incomplete occlusion. In multivariable logistic regression, significant predictors of incomplete occlusion were non-smoker status (adjusted OR 4.49, 95% CI 1.11 to 18.09; p=0.03) and side branch involvement (adjusted OR 11.68, 95% CI 3.84 to 35.50; p<0.0001), while C6 location had reduced odds of incomplete occlusion (adjusted OR 0.29, 95% CI 0.10 to 0.84; p=0.02).ConclusionsThe results of our study are consistent with previous retrospective series and warrant consideration for technique adaptations to achieve higher occlusion rates. Further follow-up is needed to assess progression of aneurysm occlusion and clinical behavior in these cases.