Dataset Information

Permeability imaging as a predictor of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

ABSTRACT: Blood-brain barrier (BBB) dysfunction has been implicated in ischemic risk following aneurysmal subarachnoid hemorrhage (aSAH), but never directly imaged. We prospectively examined whether post-bleed day 4 dynamic contrast-enhanced magnetic resonance (DCE-MR) BBB permeability imaging could predict development of delayed cerebral ischemia (DCI). Global MR-derived BBB permeability ( K_trans) was significantly higher in aSAH patients who subsequently developed DCI (five patients; 2.28 ± 0.09 × 10^-3 min^-1) compared to those who experienced radiographic vasospasm only (three patients; 1.85 ± 0.12 × 10^-3 min^-1; p < 0.05), or no vasospasm/ischemia (eight patients; 1.74 ± 0.07 × 10^-3 min^-1; p < 0.01). K_trans > 2 × 10^-3 min^-1 predicted development of DCI (AUC = 0.98, 95% CI: 0.93-1). Global BBB dysfunction following aSAH is detectable with DCE-MR and predictive of ischemic risk.

SUBMITTER: Russin JJ

PROVIDER: S-EPMC5998996 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Permeability imaging as a predictor of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Russin Jonathan J JJ Montagne Axel A D'Amore Francesco F He Shuhan S Shiroishi Mark S MS Rennert Robert C RC Depetris Jena J Zlokovic Berislav V BV Mack William J WJ

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20180403 6

Blood-brain barrier (BBB) dysfunction has been implicated in ischemic risk following aneurysmal subarachnoid hemorrhage (aSAH), but never directly imaged. We prospectively examined whether post-bleed day 4 dynamic contrast-enhanced magnetic resonance (DCE-MR) BBB permeability imaging could predict development of delayed cerebral ischemia (DCI). Global MR-derived BBB permeability ( K<sub>trans</sub>) was significantly higher in aSAH patients who subsequently developed DCI (five patients; 2.28 ± 0 ...[more]

PMID: 29611451

Similar Datasets

Project description: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. 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. 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.

Project description:ObjectiveElevated ICP is a well-recognized phenomenon in aneurysmal subarachnoid hemorrhage (aSAH) that has been demonstrated to lead to poor outcomes. Delayed cerebral ischemia (DCI) is the most important reason for a poor clinical outcome after a subarachnoid hemorrhage. DCI is understood as a multifactorial process that evolves over time, largely caused by the sequelae of increased intracranial pressure (ICP). The study aimed to assess how to better define the association between ICP and DCI, and whether rational ICP management can improve the outcome of aSAH patients.MethodsWe prospectively reviewed patients diagnosed with aSAH and received microsurgery clipping at our department from December 2019 to January 2021. Subdural ICP monitoring devices were kept to monitor the ICP. The ICP values were recorded every 1-h epochs. ICP -guided dehydration treatments were routinely performed to control the ICP level of patients after surgery. To evaluate whether the subdural ICP-directed management improved the prognosis of the aSAH patients, we compared the outcome data of the patients in our cohort with those treated at another ward of our hospital at the same period.ResultsIn total, 144 consecutive aSAH patients received microsurgery clipping at our department, 68 of whom underwent ICP monitoring. A total of 11,424 1-h ICP measurements were recorded for the included patients (1.30 years of recordings). Of 68 patients with ICP monitoring, 27 (27/68, 39.7%) patients developed DCI. Univariate analysis showed that higher Hunt-Hess grade (OR 2.138, 95% CI 1.025-4.459, p = 0.043), higher preoperative modified Rankin Scale score (OR 1.534, 95% CI 1.033-2.276, p = 0.034), and the max ICP value of each day value >28.5 mmHg (OR 4.442, 95% CI 1.509-13.082, p = 0.007) were associated with DCI. Also, patients with ICP-directed treatment showed a significantly lower DCI incidence than patients without ICP monitoring.ConclusionOur study suggests that I less than 15 mmHg possibly constitute normal values and that 28.5 mmHg is the ICP threshold most strongly associated with the occurrence of DCI in aSAH patients. Patients who received the ICP-directed treatment presented a lower incidence of DCI. Our findings provide a basis for the recommendation of ICP-directed treatment after aSAH.Trial registration numberNCT04785976.

Dataset Information

Permeability imaging as a predictor of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Publications

Permeability imaging as a predictor of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets