Non-cerebral vasospasm factors and cerebral vasospasm predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
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ABSTRACT:
SUBMITTER: Chen Y
PROVIDER: S-EPMC8769126 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Non-cerebral vasospasm factors and cerebral vasospasm predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
Chen Yue Y Li Guanmin G Chen Xiaoyong X Wang Dengliang D Fang Wenhua W Kang Dezhi D Ding Chenyu C
Chinese medical journal 20211213 2
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Project description:Precision medicine provides individualized treatment of diseases through leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage carries tremendous morbidity and mortality with cerebral vasospasm and delayed cerebral ischemia proving devastating and unpredictable. Lack of treatment measures for these conditions could be improved through precision medicine. Areas covered: Discussed are the pathophysiology of CV and DCI, treatment guidelines, and evidence for precision medicine used for prediction and prevention of poor outcomes following aSAH. A PubMed search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were evaluated. The studies presented cover biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert commentary: The biomarkers reviewed here correlate with CV, DCI, and neurologic outcomes after aSAH. Though practical use in clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine.
| S-EPMC5573230 | biostudies-other
Project description:INTRODUCTION: Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is thought to cause ischemia. To evaluate the contribution of vasospasm to delayed cerebral ischemia (DCI), we investigated the effect of vasospasm on cerebral perfusion and the relationship of vasospasm with DCI. METHODS: We studied 37 consecutive SAH patients with CT angiography (CTA) and CT perfusion (CTP) on admission and within 14 days after admission or at time of clinical deterioration. CTP values (cerebral blood volume, cerebral blood flow (CBF) and mean transit time), degree of vasospasm on CTA, and occurrence of DCI were recorded. Vasospasm was categorized as follows: no spasm (0-25% decrease in vessel diameter), moderate spasm (25-50% decrease), and severe spasm (>50% decrease). The correspondence of the flow territory of the most spastic vessel with the least perfused region was evaluated, and differences in perfusion values and occurrence of DCI between degrees of vasospasm were calculated with 95% confidence intervals (95% CI). RESULTS: Fourteen patients had no vasospasm, 16 were moderate, and seven were severe. In 65% of patients with spasm, the flow territory of the most spastic vessel corresponded with the least perfused region. There was significant CBF (milliliters per 100 g per minute) difference (-21.3; 95% CI, -37 <--> -5.3) between flow territories of severe and no vasospasm. Four of seven patients with severe, six of 16 with moderate, and three of 14 patients with no vasospasm had DCI. CONCLUSION: Vasospasm decreases cerebral perfusion, but corresponds with the least perfused region in only two thirds of our patients. Furthermore, almost half of patients with severe vasospasm do not have DCI. Thus, although severe vasospasm can decrease perfusion, it may not result in DCI.
| S-EPMC2773037 | biostudies-other
Project description:BackgroundTranscranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated.MethodsA retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed.ResultsThe Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5.ConclusionTCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements.
| S-EPMC11217085 | biostudies-literature
Project description:Background We investigated the proportion of patients in an initial good clinical condition who developed devastating DCI, and aimed to characterize these patients by aneurysm location, blood pressure instability prior to DCI, and the extent of cerebral ischemia. Methods We included aSAH patients admitted between 2010 and 2021 with a Glasgow Coma Scale of 11 or higher 24 h after aneurysm treatment, who developed devastating DCI, defined as DCI leading to coma for at least 48 h with cerebral infarction on the subsequent scan. Blood pressure instability was defined as nimodipine-induced blood pressure drops, dosage adjustments, or the use of blood pressure drugs before onset of DCI. Descriptive statistics were used to summarize the data. Results Out of 1,211 consecutive aSAH patients, 617 patients had a good clinical condition after aneurysm treatment of whom 16 (3%) patients [14 (88%) women] were included in this study. Thirteen (81%) patients had an aneurysm in the anterior circulation. Thirteen patients (81%) had blood pressure instability: twelve (75%) had nimodipine-induced blood pressure drops, eleven (69%) received antihypertensive drugs, and 7 (44%) received hypertension induction before onset of DCI. Thirteen (81%) patients had bilateral ischemia, mainly in the anterior circulation (56%). Conclusions The proportion of aSAH patients with a good clinical condition after aneurysm treatment who develop devastating DCI is small. The vast majority of these patients had blood pressure instability. Future studies are needed to investigate if a reduction in the number and extent of blood pressure fluctuations decreases the incidence of devastating DCI.
| S-EPMC9606612 | biostudies-literature
Project description:Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (SAH). Matricellular protein periostin (POSTN) has been found to be upregulated and linked with early brain injury after experimental SAH. The aim of the present study was to investigate the relationship between plasma POSTN levels and various clinical factors including serum levels of C-reactive protein (CRP), an inflammatory marker, in 109 consecutive SAH patients whose POSTN levels were measured at days 1-12 after aneurysmal obliteration. DCI developed in 16 patients associated with higher incidence of angiographic vasospasm, cerebral infarction, and 90-day worse outcomes. POSTN levels peaked at days 4-6 before DCI development. Cerebrospinal fluid (CSF) drainage was associated with reduced POSTN levels, but did not influence CRP levels. There was no correlation between POSTN levels and other treatments or CRP levels. To predict DCI development, receiver-operating characteristic curves indicated that the most reasonable cutoff POSTN levels were obtained at days 1-3 in patients without CSF drainage (80.5 ng/ml; specificity, 77.6%; sensitivity, 85.7%). Multivariate analyses using variables obtained by day 3 revealed that POSTN level was an independent predictor of DCI. POSTN levels over the cutoff value were associated with higher incidence of DCI, but not angiographic vasospasm. This study shows for the first time that CSF drainage may reduce plasma POSTN levels, and that POSTN levels may increase prior to the development of DCI with and without vasospasm irrespective of systemic inflammatory reactions in clinical settings. These findings suggest POSTN as a new therapeutic molecular target against post-SAH DCI.
| S-EPMC6554464 | biostudies-literature
Project description:Background and purposeDelayed cerebral ischemia and vasospasm are significant complications following SAH leading to cerebral infarction, functional disability, and death. In recent years, CTA and CTP have been used to increase the detection of delayed cerebral ischemia and vasospasm. Our aim was to perform comparative-effectiveness and cost-effectiveness analyses evaluating CTA and CTP for delayed cerebral ischemia and vasospasm in aneurysmal SAH from a health care payer perspective.Materials and methodsWe developed a decision model comparing CTA and CTP with transcranial Doppler sonography for detection of vasospasm and delayed cerebral ischemia in SAH. The clinical pathways were based on the "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association" (2012). Outcome health states represented mortality and morbidity according to functional outcomes. Input probabilities of symptoms and serial test results from CTA and CTP, transcranial Doppler ultrasound, and digital subtraction angiography were directly derived from an SAH cohort by using a multinomial logistic regression model. Expected benefits, measured as quality-adjusted life years, and costs, measured in 2012 US dollars, were calculated for each imaging strategy. Univariable, multivariable, and probabilistic sensitivity analyses were performed to determine the independent and combined effect of input parameter uncertainty.ResultsThe transcranial Doppler ultrasound strategy yielded 13.62 quality-adjusted life years at a cost of $154,719. The CTA and CTP strategy generated 13.89 quality-adjusted life years at a cost of $147,097, resulting in a gain of 0.27 quality-adjusted life years and cost savings of $7622 over the transcranial Doppler ultrasound strategy. Univariable and multivariable sensitivity analyses indicated that results were robust to plausible input parameter uncertainty. Probabilistic sensitivity analysis results yielded 96.8% of iterations in the right lower quadrant, representing higher benefits and lower costs.ConclusionsOur model results suggest that CTA and CTP are the preferred imaging strategy in SAH, compared with transcranial Doppler ultrasound, leading to improved clinical outcomes and lower health care costs.
| S-EPMC4161647 | biostudies-literature
Project description:BackgroundCerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role in neuroinflammation and is a suggested source of tissue injury after aneurysm rupture. This study sought to determine whether patients with subarachnoid hemorrhage and cerebral vasospasm were more likely to have been exposed to early hyperoxemia than those without vasospasm.MethodsThis single-center retrospective cohort study included adult patients presenting with aneurysmal subarachnoid hemorrhage to Vanderbilt University Medical Center between January 2007 and December 2017. Patients with an ICD-9/10 diagnosis of aneurysmal subarachnoid hemorrhage were initially identified (N = 441) and subsequently excluded if they did not have intracranial imaging, arterial PaO2 values or died within 96 h post-rupture (N = 96). The final cohort was 345 subjects. The degree of hyperoxemia was defined by the highest PaO2 measured within 72 h after aneurysmal rupture. The primary outcome was development of cerebral vasospasm, which included asymptomatic vasospasm and delayed cerebral ischemia (DCI). Secondary outcomes were mortality and modified Rankin Scale.ResultsThree hundred and forty five patients met inclusion criteria; 218 patients (63%) developed vasospasm. Of those that developed vasospasm, 85 were diagnosed with delayed cerebral ischemia (DCI, 39%). The average patient age of the cohort was 55 ± 13 years, and 68% were female. Ninety percent presented with Fisher grade 3 or 4 hemorrhage (N = 310), while 42% presented as Hunt-Hess grade 4 or 5 (N = 146). In univariable analysis, patients exposed to higher levels of PaO2 by quintile of exposure had a higher mortality rate and were more likely to develop vasospasm in a dose-dependent fashion (P = 0.015 and P = 0.019, respectively). There were no statistically significant predictors that differentiated asymptomatic vasospasm from DCI and no significant difference in maximum PaO2 between these two groups. In multivariable analysis, early hyperoxemia was independently associated with vasospasm (OR = 1.15 per 50 mmHg increase in PaO2 [1.03, 1.28]; P = 0.013), but not mortality (OR = 1.10 [0.97, 1.25]; P = 0.147) following subarachnoid hemorrhage.ConclusionsHyperoxemia within 72 h post-aneurysmal rupture is an independent predictor of cerebral vasospasm, but not mortality in subarachnoid hemorrhage. Hyperoxemia is a variable that can be readily controlled by adjusting the delivered FiO2 and may represent a modifiable risk factor for vasospasm.
| S-EPMC8093321 | biostudies-literature
Project description:BackgroundDelayed cerebral ischemia (DCI), a complication of subarachnoid hemorrhage (SAH), is linked to cerebral vasospasm and associated with poor long-term outcome. We implemented a structured cerebral microdialysis (CMD) based protocol using the lactate/pyruvate ratio (LPR) as an indicator of the cerebral energy metabolic status in the neurocritical care decision making, using an LPR ≥ 30 as a cutoff suggesting an energy metabolic disturbance. We hypothesized that CMD monitoring could contribute to active, protocol-driven therapeutic interventions that may lead to the improved management of patients with SAH.MethodsBetween 2018 and 2020, 49 invasively monitored patients with SAH, median Glasgow Coma Scale 11 (range 3-15), and World Federation of Neurosurgical Societies scale 4 (range 1-5) on admission receiving CMD were included. We defined a major CMD event as an LPR ≥ 40 for ≥ 2 h and a minor CMD event as an LPR ≥ 30 for ≥ 2 h.ResultsWe analyzed 7,223 CMD samples over a median of 6 days (5-8). Eight patients had no CMD events. In 41 patients, 113 minor events were recorded, and in 23 patients 42 major events were recorded. Our local protocols were adhered to in 40 major (95%) and 98 minor events (87%), with an active intervention in 32 (76%) and 71 (63%), respectively. Normalization of energy metabolic status (defined as four consecutive samples with LPR < 30 for minor and LPR < 40 for major events) was seen after 69% of major and 59% of minor events. The incidence of DCI-related infarcts was 10% (five patients), with only two observed in a CMD-monitored brain region.ConclusionsActive interventions were initiated in a majority of LPR events based on CMD monitoring. A low DCI incidence was observed, which may be associated with the active interventions. The potential aid of CMD in the clinical decision-making targeting DCI needs confirmation in additional SAH studies.
| S-EPMC9283139 | biostudies-literature
Project description:Approximately one-third of aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral vasospasm (DCV) 3-10 days after aneurysm rupture resulting in additional, permanent neurologic disability. Currently, no validated biomarker is available to determine the risk of DCV in aSAH patients. MicroRNAs (miRNAs) have been implicated in virtually all human diseases, including aSAH, and are found in extracellular biofluids including plasma and cerebrospinal fluid (CSF). We used a custom designed TaqMan Low Density Array miRNA panel to examine the levels of 47 selected brain and vasculature injury related miRNAs in CSF and plasma specimens collected from 31 patients with or without DCV at 3 days and 7 days after aSAH, as well as from 8 healthy controls. The analysis of the first 18-patient cohort revealed a striking differential expression pattern of the selected miRNAs in CSF and plasma of aSAH patients with DCV from those without DCV. Importantly, this differential expression was observed at the early time point (3 days after aSAH), before DCV event occurs. Seven miRNAs were identified as reliable DCV risk predictors along with a prediction model constructed based on an array of additional 19 miRNAs on the panel. These chosen miRNAs were then used to predict the risk of DCV in a separate, testing cohort of 15 patients. The accuracy of DCV risk prediction in the testing cohort reached 87%. The study demonstrates that our novel designed miRNA panel is an effective predictor of DCV risk and has strong applications in clinical management of aSAH patients.
2021-06-02 | GSE165608 | GEO
Project description:Background A subset of good-grade patients with aneurysmal subarachnoid hemorrhage (aSAH) develop delayed cerebral ischemia (DCI) that may cause permanent disabilities after aSAH. However, little is known about the risk factors of DCI among this specific patient group. Methods and Results We obtained a multinational cohort of good-grade (Glasgow Coma Scale 13-15 on admission) patients with aSAH by pooling patient data from 4 clinical trials and 2 prospective cohort studies. We collected baseline data on lifestyle-related factors and the clinical characteristics of aSAHs. By calculating fully adjusted risk estimates for DCI and DCI-related poor outcome, we identified the most high-risk patient groups. The pooled study cohort included 1918 good-grade patients with aSAH (median age, 51 years; 64% women), of whom 21% and 7% experienced DCI and DCI-related poor outcome, respectively. Among men, patients with obesity and (body mass index ≥30 kg/m2) thick aSAH experienced most commonly DCI (33%) and DCI-related poor outcome (20%), whereas none of the normotensive or young (aged <50 years) men with low body mass index (body mass index <22.5 kg/m2) had DCI-related poor outcome. In women, the highest prevalence of DCI (28%) and DCI-related poor outcome (13%) was found in patients with preadmission hypertension and thick aSAH. Conversely, the lowest rates (11% and 2%, respectively) were observed in normotensive women with a thin aSAH. Conclusions Increasing age, thick aSAH, obesity, and preadmission hypertension are risk factors for DCI in good-grade patients with aSAH. These findings may help clinicians to consider which good-grade patients with aSAH should be monitored carefully in the intensive care unit.
| S-EPMC9851459 | biostudies-literature