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Article ; Online: Drug classes affecting intracranial aneurysm risk: Genetic correlation and Mendelian randomization.

Ruigrok, Ynte M / Veldink, Jan H / Bakker, Mark K

2024 , Page(s) 23969873241234134

Abstract: Introduction: There is no non-invasive treatment to prevent aneurysmal subarachnoid hemorrhage (ASAH) caused by intracranial aneurysm (IA) rupture. We aimed to identify drug classes that may affect liability to IA using a genetic approach.: Patients ... ...

Abstract	Introduction: There is no non-invasive treatment to prevent aneurysmal subarachnoid hemorrhage (ASAH) caused by intracranial aneurysm (IA) rupture. We aimed to identify drug classes that may affect liability to IA using a genetic approach. Patients and methods: Using genome-wide association summary statistics we calculated genetic correlation between unruptured IA ( Results: Correlations with IA were found for antidepressants, paracetamol, acetylsalicylic acid, opioids, beta-blockers, and peptic ulcer and gastro-esophageal reflux disease drugs. MR showed no evidence that genetically predicted usage of these drug classes caused IA. Genetically predicted high responders to antidepressant drugs were at higher risk of IA (odds ratio [OR] = 1.61, 95% confidence interval (CI) = 1.09-2.39, Conclusions: We did not find drugs decreasing liability to IA and ASAH but found that antidepressant drugs may increase liability. We observed pleiotropic relationships between IA and other drug classes and indications. Our results improve understanding of pathogenic mechanisms underlying IA.
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2851287-X
ISSN	2396-9881 ; 2396-9873
ISSN (online)	2396-9881
ISSN	2396-9873
DOI	10.1177/23969873241234134
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Article ; Online: Management of Unruptured Cerebral Aneurysms and Arteriovenous Malformations.

Ruigrok, Ynte M

Continuum (Minneapolis, Minn.)

2020 Volume 26, Issue 2, Page(s) 478–498

Abstract: Purpose of review: Unruptured intracranial aneurysms and brain arteriovenous malformations (AVMs) may be detected as incidental findings on cranial imaging. This article provides a practical approach to the management of unruptured intracranial ... ...

Abstract	Purpose of review: Unruptured intracranial aneurysms and brain arteriovenous malformations (AVMs) may be detected as incidental findings on cranial imaging. This article provides a practical approach to the management of unruptured intracranial aneurysms and unruptured brain AVMs and reviews the risk of rupture, risk factors for rupture, preventive treatment options with their associated risks, and the approach of treatment versus observation for both types of vascular malformations. Recent findings: For unruptured intracranial aneurysms, scoring systems on the risk of rupture can help with choosing preventive treatment or observation with follow-up imaging. Although the literature provides detailed information on the complication risks of preventive treatment of unruptured intracranial aneurysms, individualized predictions of these procedural complication risks are not yet available. With observation with imaging, growth of unruptured intracranial aneurysms can be monitored, and prediction scores for growth can help determine the optimal timing of monitoring. The past years have revealed more about the risk of complications of the different treatment modalities for brain AVMs. A randomized clinical trial and prospective follow-up data have shown that preventive interventional therapy in patients with brain AVMs is associated with a higher rate of neurologic morbidity and mortality compared with observation. Summary: The risk of hemorrhage from both unruptured intracranial aneurysms and brain AVMs varies depending on the number of risk factors associated with hemorrhage. For both types of vascular malformations, different preventive treatment options are available, and all carry risks of complications. For unruptured intracranial aneurysms, the consideration of preventive treatment versus observation is complex, and several factors should be included in the decision making. Overall, it is recommended that patients with unruptured asymptomatic brain AVMs should be observed.
MeSH term(s)	Aneurysm, Ruptured/prevention & control ; Arteriovenous Fistula/diagnosis ; Arteriovenous Fistula/surgery ; Arteriovenous Fistula/therapy ; Endovascular Procedures ; Humans ; Intracranial Aneurysm/diagnosis ; Intracranial Aneurysm/surgery ; Intracranial Aneurysm/therapy ; Intracranial Arteriovenous Malformations/diagnosis ; Intracranial Arteriovenous Malformations/surgery ; Intracranial Arteriovenous Malformations/therapy ; Intracranial Hemorrhages/prevention & control ; Neurosurgical Procedures
Language	English
Publishing date	2020-03-27
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1538-6899
ISSN (online)	1538-6899
DOI	10.1212/CON.0000000000000835
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Article ; Online: Genetics of Intracranial Aneurysms.

Bakker, Mark K / Ruigrok, Ynte M

Stroke

2021 Volume 52, Issue 9, Page(s) 3004–3012

Abstract: Rupture of an intracranial aneurysm leads to aneurysmal subarachnoid hemorrhage, a severe type of stroke which is, in part, driven by genetic variation. In the past 10 years, genetic studies of IA have boosted the number of known genetic risk factors and ...

Abstract	Rupture of an intracranial aneurysm leads to aneurysmal subarachnoid hemorrhage, a severe type of stroke which is, in part, driven by genetic variation. In the past 10 years, genetic studies of IA have boosted the number of known genetic risk factors and improved our understanding of the disease. In this review, we provide an overview of the current status of the field and highlight the latest findings of family based, sequencing, and genome-wide association studies. We further describe opportunities of genetic analyses for understanding, prevention, and treatment of the disease.
MeSH term(s)	Aneurysm, Ruptured/genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study/methods ; Humans ; Intracranial Aneurysm/genetics ; Risk Factors ; Subarachnoid Hemorrhage/genetics
Language	English
Publishing date	2021-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.120.032621
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Article ; Online: Preventive screening for intracranial aneurysms.

Rinkel, Gabriel Je / Ruigrok, Ynte M

International journal of stroke : official journal of the International Stroke Society

2021 Volume 17, Issue 1, Page(s) 30–36

Abstract: Background: Subarachnoid hemorrhage from rupture of an intracranial aneurysm (aneurysmal subarachnoid hemorrhage) is a devastating subset of stroke. Since brain damage from the initial hemorrhage is a major cause for the poor outcome after aneurysmal ... ...

Abstract	Background: Subarachnoid hemorrhage from rupture of an intracranial aneurysm (aneurysmal subarachnoid hemorrhage) is a devastating subset of stroke. Since brain damage from the initial hemorrhage is a major cause for the poor outcome after aneurysmal subarachnoid hemorrhage, prevention of aneurysmal subarachnoid hemorrhage has the highest potential to prevent poor outcome from aneurysmal subarachnoid hemorrhage. Aim: In this review, we describe the groups at high risk of aneurysmal subarachnoid hemorrhage who may benefit from preventive screening for unruptured intracranial aneurysms followed by preventive treatment of unruptured intracranial aneurysms found. Furthermore, we describe the advantages and disadvantages of screening and advise how to perform counseling on screening. Summary of review: Modeling studies show that persons with two or more affected first-degree relatives with aneurysmal subarachnoid hemorrhage and patients with autosomal dominant polycystic kidney disease (ADPKD) are candidates for screening for unruptured intracranial aneurysms. One modeling study also suggests that persons with only one affected first-degree relative with aneurysmal subarachnoid hemorrhage are also likely candidates for screening. Another group who may benefit from screening are persons ≥35 years who smoke(d) and are hypertensive, given their high lifetime risk of aneurysmal subarachnoid hemorrhage of up to 7%, but the prevalence of unruptured intracranial aneurysms in such persons and the efficiency and cost-effectiveness of screening in this group are not yet known. The ultimate goal of screening is to increase the number of quality years of life of the screening candidates, and therefore the benefits but also many downsides of screening -such as risk of incidental findings, very small unruptured intracranial aneurysms that require regular follow-up, preventive treatment with inherent risk of complications and anxiety - should be discussed with the candidate so that an informed decision can be made before intracranial vessels are imaged. Conclusions: Several groups of persons who may benefit from screening have been identified, but since these constitute only a minority of all aneurysmal subarachnoid hemorrhage patients, additional high-risk groups still need to be identified. Further research is also needed to identify persons at low or high risk of aneurysmal development and rupture within the groups identified thus far to improve the efficiency of screening. Moreover, if new medical treatment strategies that can reduce the risk of rupture of unruptured intracranial aneurysm become available, the groups of persons who may benefit from screening could increase considerably.
MeSH term(s)	Aneurysm, Ruptured ; Humans ; Intracranial Aneurysm/diagnosis ; Intracranial Aneurysm/epidemiology ; Mass Screening ; Polycystic Kidney, Autosomal Dominant ; Stroke ; Subarachnoid Hemorrhage/diagnosis ; Subarachnoid Hemorrhage/epidemiology
Language	English
Publishing date	2021-06-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2303728-3
ISSN	1747-4949 ; 1747-4930
ISSN (online)	1747-4949
ISSN	1747-4930
DOI	10.1177/17474930211024584
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Article ; Online: Drivers of healthcare costs in patients with ischaemic stroke: a hospital-based retrospective cohort study.

Mensing, Liselore A / Kappelle, L Jaap / Koffijberg, Hendrik / Ruigrok, Ynte M

BMJ open

2023 Volume 13, Issue 1, Page(s) e064445

Abstract: Objectives: To evaluate how costs of healthcare can be reduced, there is an increasing need to gain insight into the main drivers of such costs. We evaluated drivers of costs of predefined subgroups of patients who had a stroke by linking cost ... ...

Abstract	Objectives: To evaluate how costs of healthcare can be reduced, there is an increasing need to gain insight into the main drivers of such costs. We evaluated drivers of costs of predefined subgroups of patients who had a stroke by linking cost registration with clinical data. Methods: We retrospectively selected 555 consecutive patients with ischaemic stroke participating between June 2011 and December 2016 in the Dutch Parelsnoer Initiative. Patient characteristics and costs of healthcare activities during hospital admission and the first 3 months after discharge were linked. Patients were divided in subgroups based on age, severity of stroke, stroke subtype, discharge destination and functional outcome. Unit cost per healthcare activity was based on 2018 rates for mutual service in euros. Mean total costs per subgroup were calculated. Multivariate analysis was performed to identify factors associated with costs. Results: Number of admitted days was the main driver of total hospital costs (range 82%-93%) in all predefined subgroups of patients. Second driver was radiological diagnostic investigations (range 2%-9%). Highest costs were observed in patients with a younger age at the time of admission, a higher modified Rankin Scale at the time of discharge and a nursing home as discharge destination. The distribution of costs over the different healthcare activities was associated with stroke subtype; for example, in patients with a cardiac embolism most costs were spent on cardiology-related healthcare activities. Conclusion: The number of admitted days was the most important driver of costs in all subgroups of patients with ischaemic stroke. This implicates that to reduce healthcare costs for patients who had a stroke, focus should be on reducing length of hospital stay.
MeSH term(s)	Humans ; Stroke/diagnosis ; Brain Ischemia/therapy ; Retrospective Studies ; Health Care Costs ; Length of Stay ; Ischemic Stroke ; Hospital Costs ; Hospitals
Language	English
Publishing date	2023-01-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-064445
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Article ; Online: Serial quality of life assessment around screening for familial intracranial aneurysms: a prospective cohort study.

Mensing, Liselore A / Atash, Keneshka / Rinkel, Gabriel Je / Ruigrok, Ynte M

Cerebrovascular diseases (Basel, Switzerland)

2023

Abstract: Introduction: Screening for intracranial aneurysms (IAs) is cost-effective in first-degree relatives of aneurysmal subarachnoid haemorrhage (aSAH) patients, but its psychosocial impact is largely unknown.: Patients and methods: A consecutive series ... ...

Abstract	Introduction: Screening for intracranial aneurysms (IAs) is cost-effective in first-degree relatives of aneurysmal subarachnoid haemorrhage (aSAH) patients, but its psychosocial impact is largely unknown. Patients and methods: A consecutive series of persons aged 20-70 years visiting the University Medical Centre Utrecht for first screening for familial IA was approached between 2017-2020. E-questionnaires were administered at six time points, consisting of the EQ-5D for health-related quality of life (QoL), HADS for emotional functioning and USER-P for social participation. QoL outcomes were compared with the general population, and between participants with a positive and negative screening for IA. Predictors of QoL outcomes were assessed with linear mixed effects models. Results: 105 participants from 75 families were included; in 10 (10%) an IA was found. During the first year after screening we found no negative effect on QoL, except for a temporary decrease in QoL six months after screening in participants with a positive screen (EQ-5D -11.3 [95%CI:-21.7 to -0.8]). Factors associated with worse QoL were psychiatric disease (EQ-5D -10.3 [95%CI:-15.1 to -5.6]), physical complaints affecting mood (EQ-5D -8.1 [95%CI:-11.7 to -4.4]), and a passive coping style (EQ-5D decrease per point increase on the Utrecht Coping List -1.1 [95%CI:-1.5 to -0.6]). Discussion and conclusion: We did not find a lasting negative effect on QoL during the first year after screening for familial IA. Predictors for a worse QoL were psychiatric disease, physical complaints affecting mood, and a passive coping style. This information can be used in counselling about familial IA screening.
Language	English
Publishing date	2023-10-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1069462-6
ISSN	1421-9786 ; 1015-9770
ISSN (online)	1421-9786
ISSN	1015-9770
DOI	10.1159/000534373
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Zs.A 3181: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Graph convolutional networks for automated intracranial artery labeling.

Vos, Iris N / Ruigrok, Ynte M / Bhat, Ishaan R / Timmins, Kimberley M / Velthuis, Birgitta K / Kuijf, Hugo J

Journal of medical imaging (Bellingham, Wash.)

2024 Volume 11, Issue 1, Page(s) 14007

Abstract: Purpose: Unruptured intracranial aneurysms (UIAs) can cause aneurysmal subarachnoid hemorrhage, a severe and often lethal type of stroke. Automated labeling of intracranial arteries can facilitate the identification of risk factors associated with UIAs. ...

Abstract	Purpose: Unruptured intracranial aneurysms (UIAs) can cause aneurysmal subarachnoid hemorrhage, a severe and often lethal type of stroke. Automated labeling of intracranial arteries can facilitate the identification of risk factors associated with UIAs. This study aims to improve intracranial artery labeling using atlas-based features in graph convolutional networks. Approach: We included three-dimensional time-of-flight magnetic resonance angiography scans from 150 individuals. Two widely used graph convolutional operators, GCNConv and GraphConv, were employed in models trained to classify 12 bifurcations of interest. Cross-validation was applied to explore the effectiveness of atlas-based features in node classification. The results were tested for statistically significant differences using a Wilcoxon signed-rank test. Model repeatability and calibration were assessed on the test set for both operators. In addition, we evaluated model interpretability and node feature contribution using explainable artificial intelligence. Results: Atlas-based features led to statistically significant improvements in node classification ( Conclusions: The addition of atlas-based features improved node classification results. The GraphConv operator, which incorporates higher-order structural information during training, is recommended over the GCNConv operator based on the accuracy and calibration of predicted outcomes.
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ISSN	2329-4302
ISSN	2329-4302
DOI	10.1117/1.JMI.11.1.014007
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Article ; Online: Development of a questionnaire to identify persons with a family history of aneurysmal subarachnoid hemorrhage.

Zuurbier, Charlotte Cm / Greving, Jacoba P / Rinkel, Gabriel Je / Ruigrok, Ynte M

International journal of stroke : official journal of the International Stroke Society

2022 Volume 17, Issue 10, Page(s) 1100–1106

Abstract: Background: Preventive screening for intracranial aneurysms is effective in persons with a positive family history of aneurysmal subarachnoid hemorrhage (aSAH), but for many relatives of aSAH patients, it can be difficult to assess whether their ... ...

Abstract	Background: Preventive screening for intracranial aneurysms is effective in persons with a positive family history of aneurysmal subarachnoid hemorrhage (aSAH), but for many relatives of aSAH patients, it can be difficult to assess whether their relative had an aSAH or another type of stroke. Aim: We aimed to develop a family history questionnaire for people in the population who believe they have a first-degree relative who had a stroke and to assess its accuracy to identify relatives of aSAH patients. Methods: A questionnaire to distinguish between aSAH and other stroke types (ischemic stroke and intracerebral hemorrhage) was developed by a team of clinicians and consumers. The level of agreement between the questionnaire outcome and medical diagnosis was pilot tested in 30 previously admitted aSAH patients. Next, the sensitivity and specificity of the questionnaire were assessed in 91 first-degree relatives (siblings/children) of previously admitted stroke patients. Results: All 30 aSAH patients were identified by the questionnaire in the pilot study; 29 of 30 first-degree relatives of aSAH patients were correctly identified. The questionnaire had a sensitivity of 97% (95% confidence interval (CI) = 83-100%) and a specificity of 93% (95% CI = 84-98%) when tested in the first-degree relatives of stroke patients. Conclusion: Our questionnaire can help persons to discriminate an aSAH from other types of stroke in their affected relative. This family history questionnaire is developed in the Netherlands but could also be used in other countries after validation.
MeSH term(s)	Humans ; Child ; Subarachnoid Hemorrhage/diagnosis ; Subarachnoid Hemorrhage/genetics ; Subarachnoid Hemorrhage/epidemiology ; Pilot Projects ; Stroke/diagnosis ; Stroke/genetics ; Intracranial Aneurysm/epidemiology ; Surveys and Questionnaires
Language	English
Publishing date	2022-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2303728-3
ISSN	1747-4949 ; 1747-4930
ISSN (online)	1747-4949
ISSN	1747-4930
DOI	10.1177/17474930211069004
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Article: Imaging markers of intracranial aneurysm development: A systematic review.

Kancheva, Angelina K / Velthuis, Birgitta K / Ruigrok, Ynte M

Journal of neuroradiology = Journal de neuroradiologie

2021 Volume 49, Issue 2, Page(s) 219–224

Abstract: Background: Imaging markers of intracranial aneurysm (IA) development are not well established.: Purpose: To provide an overview of imaging markers of IA development.: Methods: A systematic search of PubMed and Embase up to December 1st 2020 using ...

Abstract	Background: Imaging markers of intracranial aneurysm (IA) development are not well established. Purpose: To provide an overview of imaging markers of IA development. Methods: A systematic search of PubMed and Embase up to December 1st 2020 using predefined criteria. Thirty-six studies met our inclusion criteria. We performed a quantitative summary of the included studies. Results: We found converging evidence for A1 segment asymmetry as an anatomical marker of anterior communicating artery (Acom) aneurysm development, and moderate evidence for several other markers. No hemodynamic markers yielded converging or moderate evidence. There was large heterogeneity across studies, especially in the definitions of imaging markers and study outcomes used. Due to the poor methodological quality of many studies and unavailability of effect sizes or crude data to calculate effect sizes, a formal meta-analysis was not possible. Conclusions: We only identified A1 segment asymmetry as an imaging marker of Acom aneurysm development with converging evidence. A meta-analysis was not possible due to the heterogeneity of marker definitions and outcomes used, and poor methodological quality of many studies. Future studies should use robust study designs and uniformly defined imaging markers and outcome measures.
MeSH term(s)	Anterior Cerebral Artery ; Diagnostic Imaging ; Humans ; Intracranial Aneurysm/diagnostic imaging ; Outcome Assessment, Health Care
Language	English
Publishing date	2021-10-08
Publishing country	France
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	131763-5
ISSN	1773-0406 ; 0150-9861
ISSN (online)	1773-0406
ISSN	0150-9861
DOI	10.1016/j.neurad.2021.09.001
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Article ; Online: Anti-Epileptic Drug Target Perturbation and Intracranial Aneurysm Risk: Mendelian Randomization and Colocalization Study.

Bakker, Mark K / van Straten, Tijmen / Chong, Michael / Paré, Guillaume / Gill, Dipender / Ruigrok, Ynte M

Stroke

2022 Volume 54, Issue 1, Page(s) 208–216

Abstract: Background: In a genome-wide association study of intracranial aneurysms (IA), enrichment was found between genes associated with IA and genes encoding targets of effective anti-epileptic drugs. Our aim was to assess if this pleiotropy is driven by ... ...

Abstract	Background: In a genome-wide association study of intracranial aneurysms (IA), enrichment was found between genes associated with IA and genes encoding targets of effective anti-epileptic drugs. Our aim was to assess if this pleiotropy is driven by shared disease mechanisms that could potentially highlight a treatment strategy for IA. Methods: Using 2-sample inverse-variance weighted Mendelian randomization and genetic colocalization analyses we assessed: (1) if epilepsy liability in general affects IA risk, and (2) whether changes in gene- and protein-expression levels of anti-epileptic drug targets in blood and arterial tissue may causally affect IA risk. Results: We found no overall effect of epilepsy liability on IA. Expression of 21 genes and 13 proteins corresponding to anti-epileptic drug targets supported a causal effect ( Conclusions: CNNM2
MeSH term(s)	Humans ; Intracranial Aneurysm/drug therapy ; Intracranial Aneurysm/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Genetic Predisposition to Disease/genetics ; Epilepsy/drug therapy ; Epilepsy/genetics ; Polymorphism, Single Nucleotide/genetics ; Risk Factors
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.122.040598
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