Validation of a cerebral hemodynamic model with personalized calibration in patients with aneurysmal subarachnoid hemorrhage

This study aims to validate a numerical model developed for assessing personalized circle of Willis (CoW) hemodynamics under pathological conditions. Based on 66 computed tomography angiography images, investigations were obtained from 43 acute aneurysmal subarachnoid hemorrhage (aSAH) patients from a local neurovascular center. The mean flow velocity of each artery in the CoW measured using transcranial Doppler (TCD) and simulated by the numerical model was obtained for comparison. The intraclass correlation coefficient (ICC) over all cerebral arteries for TCD and the numerical model was 0.88 (N = 561; 95% CI 0.84–0.90). In a subgroup of patients who had developed delayed cerebral ischemia (DCI), the ICC had decreased to 0.72 but remained constant with respect to changes in blood pressure, Fisher grade, and location of ruptured aneurysm. Our numerical model showed good agreement with TCD in assessing the flow velocity in the CoW of patients with aSAH. In conclusion, the proposed model can satisfactorily reproduce the cerebral hemodynamics under aSAH conditions by personalizing the numerical model with TCD measurements. Clinical trial registration: [http://www.trialregister.nl/], identifier [NL8114]

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a non-invasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data is available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in non-traumatic SAH patients with the occurrence of DCI and functional outcome at two months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, world federation of neurosurgical societies after REsuscitation).METHODS: In this study, the rSO2 distribution of patient with and without DCI after SAH are compared. The optimal cutoff points to predict DCI and outcome are assessed, and its predictive value is compared to the SAFIRE grade.RESULTS: Out of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve (AUC) of 0.77 (95%CI 0.62-0.92; p=0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an AUC of 0.86 (95%CI 0.74-0.98; p=0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade.CONCLUSION: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.</p

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a non-invasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data is available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in non-traumatic SAH patients with the occurrence of DCI and functional outcome at two months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, world federation of neurosurgical societies after REsuscitation).METHODS: In this study, the rSO2 distribution of patient with and without DCI after SAH are compared. The optimal cutoff points to predict DCI and outcome are assessed, and its predictive value is compared to the SAFIRE grade.RESULTS: Out of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve (AUC) of 0.77 (95%CI 0.62-0.92; p=0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an AUC of 0.86 (95%CI 0.74-0.98; p=0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade.CONCLUSION: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.</p

The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage

Background and purpose: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. Methods: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient. Results: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79–0.99), DCI 0.68 (95% CI 0.50–0.87) and functional outcome 0.74 (95% CI 0.57–0.91). Cohen's kappa between the two raters was moderate to substantial (0.57–0.63). Conclusions: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression