Gabriel J E Rinkel's research while affiliated with University Medical Center Utrecht and other places
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Publications (606)
The pathophysiology and treatment of post-stroke cognitive impairment (PSCI) are not clear. Stroke triggers an inflammatory response, which might affect synapse function and cognitive status. We performed a systematic review and meta-analysis to assess whether patients with PSCI have increased levels of inflammatory markers and whether anti-inflamm...
Background and purpose
Aneurysmal subarachnoid hemorrhage (ASAH) is a complex disease with higher incidence in women compared to men and in Japan compared to other countries. It was hypothesized that ASAH is consistent with a multistep model of disease. The following assessments were made: (1) the number of steps needed for the disease to occur and...
Neuroinflammation and microthrombosis may be underlying mechanisms of brain injury after aneurysmal subarachnoid hemorrhage (aSAH), but they have not been studied in relation to each other. In postmortem brain tissue, we investigated neuroinflammation by studying the microglial and astrocyte response in the frontal cortex of 11 aSAH and 10 control...
Background and objectives
Screening for unruptured intracranial aneurysms (UIAs) is effective for first degree relatives (FDRs) of aneurysmal subarachnoid hemorrhage (aSAH) patients. Whether screening is also effective for FDRs of UIA patients is unknown. We determined the yield of screening in such FDRs, assessed rupture risk and treatment decisio...
Aneurysmal subarachnoid hemorrhage is a medical emergency that necessitates direct transfer to a tertiary referral center specialized in the diagnosis and treatment of this condition. The initial hours after aneurysmal rupture are critical for patients with aneurysmal subarachnoid hemorrhage, both in terms of rebleeding and combating the effect of...
Background:
Hypertension-induction is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid haemorrhage (aSAH), however, high-quality studies on its efficacy are lacking. We studied immediate and 3-/6-month clinical efficacy of hypertension-induction in aSAH patients with clinical DCI.
Methods:
A retrospective...
Background:
External ventricular drainage (EVD) for acute hydrocephalus after aneurysmal subarachnoid haemorrhage (aSAH) carries a risk of complications. We studied the proportion of patients in whom EVD can be avoided by treating acute hydrocephalus with ≥1 lumbar punctures (LP).
Methods:
From a prospectively collected database, we retrieved da...
Background:
In first-degree relatives of patients with aneurysmal subarachnoid hemorrhage (aSAH), the risk of an intracranial aneurysm can be predicted at initial screening but not at follow-up screening. We aimed to develop a model for predicting the probability of a new intracranial aneurysm after initial screening in people with a positive fami...
Background:
Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined...
Introduction and objective
Blood pressure is presumably related to rebleeding and delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (aSAH) and could serve as a target to improve outcome. We assessed the associations between blood pressure and rebleeding or DCI in aSAH-patients.
Materials and methods
In this observational study in 1167...
Background and Objectives
The ULTRA-trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at six months. An expected proportion of the included patients had non-aneurysmal subarachnoid hemorrhage In this post-hoc study, we will investigate whether ultra-early and short-...
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...
An amendment to this paper has been published and can be accessed via the original article.
Objective
Preventive unruptured intracranial aneurysm occlusion can reduce the risk of subarachnoid hemorrhage, but both endovascular and microneurosurgical treatment carry a risk of serious complications. To improve individualized management decisions, we developed risk scores for complications of endovascular and microneurosurgical treatment base...
Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of...
Background
Our randomized clinical trial on induced hypertension in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) was halted prematurely due to unexpected slow recruitment rates. This raised new questions regarding recruitment feasibility. As our trial can therefore be seen as a feasibility trial, we...
Background
The appropriate management of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains uncertain. We aimed to evaluate the effect of implementing a standardized protocol for detection and management of DCI after aSAH on cerebral infarction and functional outcome.
Methods
We studied two cohorts of aSAH pati...
Objective:
In counselling patients with an unruptured intracranial aneurysm (UIA), quality-of-life (QoL) outcomes are important for informed decision-making. We evaluated QoL outcomes in patients with and without preventive aneurysm occlusion at multiple time points during the first year after UIA diagnosis and studied predictors of QoL outcomes....
Background
Rupture of an intracranial aneurysm (IA) causes aneurysmal subarachnoid hemorrhage (ASAH). There is no accurate prediction model for IA or ASAH in the general population. Recent discoveries in genetic risk for IA may allow improved risk prediction.
Methods
We constructed a genetic risk score including genetic association data for IA and...
In patients with spontaneous intracerebral hemorrhage caused by different vasculopathies, cerebral microinfarcts have the same aspect on MRI and the same applies to cerebral microbleeds. It is unclear what pathological changes underlie these cerebral microinfarcts and cerebral microbleeds. In the current study, we explored the histopathological sub...
Blood pressure (BP) elevations often complicate the management of intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage, the most serious forms of acute stroke. Despite consensus on potential benefits of BP lowering in the acute phase of intracerebral hemorrhage, controversies persist over the timing, mechanisms, and approaches to treatme...
Rupture of an intracranial aneurysm (IA) leads to aneurysmal subarachnoid haemorrhage (ASAH), a severe type of stroke. Some rare variants that cause IA in families have been identified, but still, the majority of genetic causes, as well as the biological mechanisms of IA development and rupture, remain unknown. We aimed to identify rare, damaging v...
Background
High systolic blood pressure (SBP) after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with an increased risk of rebleeding. It remains unclear if an SBP lowering strategy before aneurysm treatment decreases this risk without increasing the risk of a delayed cerebral ischemia (DCI). Therefore, we compared the rates of in-...
Background
Persons with a positive family history of aneurysmal subarachnoid hemorrhage are at increased risk of aneurysmal subarachnoid hemorrhage. Preventive screening for intracranial aneurysms (IAs) in these persons is cost-effective but not very efficient. We aimed to develop and externally validate a model for predicting the probability of an...
Background:
Increased cerebral blood-flow pulsatility is associated with cerebral small vessel disease (cSVD). Reduced pulsatility attenuation over the internal carotid artery (ICA) could be a contributing factor to the development of cSVD and could be associated with intracranial ICA calcification (iICAC).
Purpose:
To compare pulsatility, pulsa...
Background and purpose:
In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed s...
Background and purpose:
Whether certain activities can trigger spontaneous intracerebral hemorrhage (ICH) remains unknown. Insights into factors that trigger vessel rupture resulting in ICH improves knowledge on the pathophysiology of ICH. We assessed potential trigger factors and their risk for ICH onset.
Methods:
We included consecutive patien...
Background
In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding anticoagulation is the best long-term strategy to prevent recurrent stroke and other vascular events. In APACHE-AF, we aimed to estimate the rates of non-fatal...
Background
In some acute care trials, immediate informed consent is not possible, but deferred consent is often considered problematic. We investigated the opinions of patients, proxies, and physicians about deferred consent in an acute stroke trial to gain insight into its acceptability and effects.
Methods
Paper-based surveys were sent to patien...
We compared velocity pulsatility, distensibility, and pulsatility attenuation along the intracranial ICA and MCA between 50 patients with pseudoxanthoma elasticum and 40 controls. Patients with pseudoxanthoma elasticum had higher pulsatility and lower distensibility at all measured locations, except for a similar distensibility at C4. The pulsatili...
Importance
The Restart or Stop Antithrombotics Randomized Trial (RESTART) found that antiplatelet therapy appeared to be safe up to 5 years after intracerebral hemorrhage (ICH) that had occurred during antithrombotic (antiplatelet or anticoagulant) therapy.
Objectives
To monitor adherence, increase duration of follow-up, and improve precision of e...
Importance
Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with an increase in risk of rupture. However, the absolute risk of aneurysm rupture after detection of growth remains unclear.
Objective
To determine the ab...
Background:
The Nationwide Inpatient Sample Subarachnoid Hemorrhage (SAH) Severity Score (NIS-SSS) was developed as a measure of SAH severity for use in administrative databases. The NIS-SSS consists of International Classification of Diseases Ninth Revision (ICD-9) diagnostic and procedure codes derived from the SAH inpatient course and has been...
Objective:
Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based me...
Background and Purpose
The computed tomography angiography spot sign is associated with hematoma expansion, case fatality, and poor functional outcome in spontaneous supratentorial intracerebral hemorrhage (ICH). However, no data are available on the spot sign in spontaneous cerebellar ICH.
Methods
We investigated consecutive patients with spontan...
Background: Many randomized controlled trials (RCT) have assessed new treatments in subarachnoid hemorrhage (SAH), yet most show no treatment efficacy. One explanation is the statistical analysis of the primary endpoint was not as efficient as possible. We reanalyzed SAH RCTs with various statistical tests to determine whether the statistical metho...
Background:
In patients with spontaneous cerebellar intracerebral hemorrhage (ICH) guidelines advocate evacuation when the hematoma diameter is > 3 cm. We studied outcome in patients with cerebellar ICH > 3 cm who did not undergo immediate hematoma evacuation.
Methods:
We included consecutive patients with cerebellar ICH > 3 cm at two academic h...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Background
In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year risks of rupture based on six easily retrievable patient and aneurysm characteristics. We assessed whether management decisions on UIAs changed after imple...
Background
In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6...
Introduction: One of the foremost challenges in subarachnoid hemorrhage (SAH) management is understanding which patient characteristics and treatment decisions lead to good outcomes. This study uses novel game theory-based methods in explainable machine learning (ML) and propensity-score matching to elucidate the clinical factors driving outcomes f...
Background
The inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischaemia, poor functional outcome, and case fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement compon...
Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of whic...
Background
Attenuation of velocity pulsatility along the internal carotid artery (ICA) is deemed necessary to protect the microvasculature of the brain. The role of the carotid siphon within the whole ICA trajectory in pulsatility attenuation is still poorly understood. This study aims to assess arterial variances in velocity pulsatility and disten...
Background
A previous study suggested that intracranial aneurysms are more likely to occur in the same arterial territory within families. We aimed to replicate this analysis in independent families and in a sample limited to intracranial aneurysms that ruptured.
Methods
Among families with ≥2 first-degree relatives with intracranial aneurysms, we...
Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of ane...
Objective
To conduct a systematic review and meta-analysis of studies reporting on risk factors according to the location of the intracerebral hemorrhage.
Methods
We searched PubMed and Embase for cohort and case-control studies reporting on ≥100 patients with spontaneous intracerebral hemorrhage, that specified the location of the hematoma and re...
Background
Patients undergoing cerebral bypass surgery are prone to cerebral hypoperfusion. Currently, arterial blood pressure is often increased with vasopressors to prevent cerebral ischaemia. However, this might cause vasoconstriction of the graft and cerebral vasculature and decrease perfusion. We hypothesised that cardiac output, rather than a...
Background
The inflammatory response after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischemia, poor functional outcome, and case-fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduce brain injury with approximately 40%. Complement component...
Background The inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischemia, poor functional outcome, and case-fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement compone...
Background and purpose:
In patients with SAH, the amount of blood is strongly associated with clinical outcome. However, it is commonly estimated with a coarse grading scale, potentially limiting its predictive value. Therefore, we aimed to develop and externally validate prediction models for clinical outcome, including quantified blood volumes,...
Background
Aneurysmal subarachnoid hemorrhage (aSAH) patients have an inflammatory response in the cerebrospinal fluid (CSF). We determined CSF cell counts, erythrocyte/leukocyte ratio, and glucose- and protein concentrations in patients ≤20 days after aSAH without bacterial meningitis. Such knowledge may help to interpret CSF parameters in patient...
Abstract Background Recurrent bleeding from an intracranial aneurysm after subarachnoid hemorrhage (SAH) is associated with unfavorable outcome. Recurrent bleeding before aneurysm occlusion can be performed occurs in up to one in five patients and most often happens within the first 6 h after the primary hemorrhage. Reducing the rate of recurrent b...
Background and purpose
Previously, we showed that co-prevalence of extracranial carotid artery aneurysms (ECAAs) in patients with intracranial aneurysms (IAs) was 2% in a Dutch cohort. In order to obtain more precise estimates and discover potential predictors of ECAA co-prevalence in the European population, we retrospectively compared differences...
Background:
Guidelines regarding recommendations for surgical treatment of spontaneous cerebellar intracerebral haemorrhage (ICH) differ. We aimed to systematically review the literature to assess treatment strategies and outcomes.
Methods:
We searched PubMed and Embase between 1970 and 2019 for randomised or otherwise controlled studies and obs...
Background and Purpose—
Interventional treatment of unruptured brain arteriovenous malformations (BAVMs) has become increasingly controversial. Because medical therapy is still lacking, we aimed to obtain insight into the disease mechanisms implicated in BAVMs and to identify potential targets for medical treatment to prevent rupture of a BAVM.
Me...
Objective:
To investigate to what extent low-frequency genetic variants (with minor allele frequencies <5%) affect the risk of intracranial aneurysms (IAs).
Methods:
One thousand fifty-six patients with IA and 2,097 population-based controls from the Netherlands were genotyped with the Illumina HumanExome BeadChip. After quality control (QC) of...
Background and purpose:
Prediction of intracranial aneurysm growth risk can assist physicians in planning of follow-up imaging of conservatively managed unruptured intracranial aneurysms. We therefore aimed to externally validate the ELAPSS (Earlier subarachnoid hemorrhage, aneurysm Location, Age, Population, aneurysm Size and Shape) score for pre...
Background
Cerebral ischaemia is thought to be an important determinant of cognitive outcome after aneurysmal subarachnoid haemorrhage (aSAH), but the exact relationship is unclear. We studied the effect of ischaemic brain lesions during clinical course on cognitive outcome 2 months after aSAH.
Methods
We studied 74 consecutive patients admitted t...
Background and Purpose—
Finding adequate control tissue for intracranial aneurysm (IA) pathophysiological studies, including gene expression studies, can be challenging. We compared gene expression profiles of superficial temporal, cortical, and circle of Willis (CoW) arteries and IA in search of the most optimal control tissue for future experimen...
Background and purpose:
Previous studies have suggested that gadolinium enhancement of the wall of unruptured intracranial aneurysms on MR imaging may reflect aneurysm wall instability. However, all previous studies were cross-sectional. In this longitudinal study, we investigated whether aneurysm wall enhancement is associated with an increased r...
Background
We previously showed that intracranial aneurysm (IA)–associated single‐nucleotide polymorphisms are enriched in promoters and putative enhancers identified in the human circle of Willis, on which IAs develop, suggesting a role for promoters and enhancers in IAs. We further investigated the role of putative enhancers in the pathogenesis o...
Intracranial aneurysms (IAs) develop more often on bifurcations compared with the rest of the circle of Willis (CoW). We investigated histological differences between 2 high IA prevalence sites (anterior communicating artery [AcomA] and basilar tip) and 2 corresponding low IA prevalence sites (anterior cerebral artery [ACA] and basilar artery [BA])...
Background:
Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but...
Background:
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greate...
Background and Purpose
A much higher rupture rate for patients with familial intracranial aneurysms (IA) compared with patients with sporadic IA has been reported in a study with highly selected familial aneurysms using sporadic patients from other populations a controls. We aimed to validate these findings in a large independent series of Dutch pa...
Table S1. Characteristics of CoW Donors and Use of CoW Tissue
Table S2. Primers for 4C Experiments
Table S3. Quality Assessment of 4C Datasets
Table S4. Primers Used for Testing Enhancer Activity in Zebrafish
Table S5. Primers Used to Make Antisense RNA Probes for In Situ Hybridization
Table S6. Identified Contacts Between Putative Enhancers a...
Assessment of publication bias.
(DOCX)
Sensitivity analysis high quality studies only.
Results of the comparison of patient and aneurysm-specific characteristics for ruptured and unruptured aneurysms.
(DOCX)
Background and purpose
Patient and aneurysm characteristics have been reported to differ between patients with familial and non-familial intracranial aneurysms (IAs), although results are inconsistent. We systematically reviewed and meta-analyzed the literature to identify and quantify patient- and aneurysm characteristics associated with familial...
Sensitivity analysis high quality studies only.
Results of the comparison of patient and aneurysm-specific characteristics for ruptured aneurysms only.
(DOCX)
Sensitivity analysis excluding Finnish and Inuit populations.
Results of the comparison of patient and aneurysm-specific characteristics for ruptured aneurysms only.
(DOCX)