Background and ObjectivesScreening for unruptured intracranial aneurysms (UIAs) is effective for first-degree relatives(FDRs) of patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether... Show moreBackground and ObjectivesScreening for unruptured intracranial aneurysms (UIAs) is effective for first-degree relatives(FDRs) of patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether screening isalso effective for FDRs of patients with UIA is unknown. We determined the yield of screening insuch FDRs, assessed rupture risk and treatment decisions of aneurysms that were found, iden-tified potential high-risk subgroups, and studied the effects of screening on quality of life (QoL).MethodsIn this prospective cohort study, we included FDRs, aged 20–70 years, of patients with UIAwithout a family history of aSAH who visited the Neurology outpatient clinic in 1 of 3 partici-pating tertiary referral centers in the Netherlands. FDRs were screened for UIA with magneticresonance angiography between 2017 and 2021. We determined UIA prevalence and developed aprediction model for UIA risk at screening using multivariable logistic regression. QoL wasevaluated with questionnaires 6 times during the first year after screening and assessed with alinear mixed-effects model.ResultsWe detected 24 UIAs in 23 of 461 screened FDRs, resulting in a 5.0% prevalence (95% CI3.2–7.4). The median aneurysm size was 3 mm (interquartile range [IQR] 2–4 mm), and themedian 5-year rupture risk assessed with the PHASES score was 0.7% (IQR 0.4%–0.9%). AllUIAs received follow-up imaging, and none were treated preventively. After a median follow-up of24 months (IQR 13–38 months), no UIA had changed. Predicted UIA risk at screening rangedbetween 2.3% and 14.7% with the highest risk in FDRs who smoke and have excessive alcoholconsumption (c-statistic: 0.76; 95% CI 0.65–0.88). At all survey moments, health-related QoLand emotional functioning were comparable with those in a reference group from the generalpopulation. One FDR with a positive screening result expressed regret about screening.DiscussionBased on the current data, we do not advise screening FDRs of patients with UIA becauseall identified UIAs had a low rupture risk. We observed no negative effect of screening on QoL. Alonger follow-up should determine the risk of aneurysm growth requiring preventive treatment. Show less
Algra, A.M.; Greving, J.P.; Wermer, M.J.H.; Walderveen, M.A.A. van; Schaaf, I.C. van der; Zwan, A. van der; ... ; Vergouwen, M.D.I. 2022
Background and Objectives In counseling patients with an unruptured intracranial aneurysm (UIA), quality of life (QoL) outcomes are important for informed decision making. We evaluated QoL outcomes... Show moreBackground and Objectives In counseling 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. Methods We performed a prospective cohort study in patients aged >= 18 years with a newly diagnosed UIA in 2 tertiary referral centers in the Netherlands between 2017 and 2019. Patients were sent QoL questionnaires at 7 (aneurysm occlusion) or 5 (no occlusion) moments during the first year after diagnosis. We collected baseline data on patient and aneurysm characteristics, passive coping style (Utrecht Coping List), occlusion modality, and neurologic complications. We assessed health-related QoL (HRQoL) with the EuroQol 5 dimensions (EQ-5D), emotional functioning with the Hospital Anxiety and Depression Scale (HADS), and restrictions in daily activities with the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). We used a linear mixed-effects model to assess the course of QoL over time and to explore predictors of QoL outcomes. Results Of 153 eligible patients, 99 (65%) participated, of whom 30/99 (30%) underwent preventive occlusion. Patients undergoing occlusion reported higher baseline levels of passive coping, anxiety and depression, and restrictions than patients without occlusion. During recovery after occlusion, patients reported more restrictions compared with baseline (adjusted USER-P decrease 1 month post occlusion: -12.8 [95% CI -23.8 to -1.9]). HRQoL and emotional functioning gradually improved after occlusion (EQ-5D increase at 1 year: 8.6 [95% CI 0.1-17.0] and HADS decrease at 1 year: -5.4 [95% CI -9.4 to -1.5]). In patients without occlusion, the largest HRQoL improvement occurred directly after visiting the outpatient aneurysm clinic (EQ-5D increase: 9.2 [95% CI 5.5-12.8]). At 1 year, QoL outcomes were comparable in patients with and without occlusion. Factors associated with worse QoL outcomes were a passive coping style in all patients, complications in patients with occlusion, and higher rupture risks in patients without occlusion. Discussion After UIA diagnosis, QoL improves gradually after preventive occlusion and directly after counseling at the outpatient clinic in patients without occlusion, resulting in comparable 1-year QoL outcomes. A passive coping style is an important predictor of poor QoL outcomes in all patients with UIA. Show less
Introduction We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge... Show moreIntroduction We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge in Dutch comprehensive stroke centers. Furthermore, we studied the association between COVID-19-status and treatment times. Methods We included all patients receiving reperfusion treatment in 17 Dutch stroke centers from May 11th, 2017, until May 11th, 2020. We collected baseline characteristics, National Institutes of Health Stroke Scale (NIHSS) at admission, onset-to-door time (ODT), door-to-needle time (DNT), door-to-groin time (DGT) and COVID-19-status at admission. Parameters during the lockdown (March 15th, 2020 until May 11th, 2020) were compared with those in the same period in 2019, and between groups stratified by COVID-19-status. We used nationwide data and extrapolated our findings to the increasing trend of EVT numbers since May 2017. Results A decline of 14% was seen in reperfusion treatments during lockdown, with a decline in both IVT and EVT delivery. DGT increased by 12 min (50 to 62 min, p-value of < 0.001). Furthermore, median NIHSS-scores were higher in COVID-19 - suspected or positive patients (7 to 11, p-value of 0.004), door-to-treatment times did not differ significantly when stratified for COVID-19-status. Conclusions During the first surge of the COVID-19 pandemic, a decline in acute reperfusion treatments and a delay in DGT was seen, which indicates a target for attention. It also appeared that COVID-19-positive or -suspected patients had more severe neurologic symptoms, whereas their EVT-workflow was not affected. Show less
Kamp, L.T. van der; Rinkel, G.J.E.; Verbaan, D.; Berg, R. van den; Vandertop, W.P.; Murayama, Y.; ... ; Vergouwen, M.D.I. 2021
IMPORTANCE Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with... Show moreIMPORTANCE 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 absolute risk of rupture of an aneurysm after detection of growth during follow-up and to develop a prediction model for rupture.DESIGN, SETTING, AND PARTICIPANTS Individual patient datawere obtained from 15 international cohorts. Patients 18 years and older who had follow-up imaging for at least 1 untreated unruptured intracranial aneurysm with growth detected at follow-up imaging and with 1 day or longer of follow-up after growth were included. Fusiform or arteriovenous malformation-related aneurysms were excluded. Of the 5166 eligible patients who had follow-up imaging for intracranial aneurysms, 4827 were excluded because no aneurysm growth was detected, and 27 were excluded because they had less than 1 day follow-up after detection of growth.EXPOSURES All included aneurysms had growth, defined as 1mmor greater increase in 1 direction at follow-up imaging.MAIN OUTCOMES AND MEASURES The primary outcomewas aneurysm rupture. The absolute risk of rupture was measured with the Kaplan-Meier estimate at 3 time points (6 months, 1 year, and 2 years) after initial growth. Cox proportional hazards regression was used to identify predictors of rupture after growth detection. RESULTS A total of 312 patients were included (223 [71%] were women; mean [SD] age, 61 [12] years) with 329 aneurysms with growth. During 864 aneurysm-years of follow-up, 25 (7.6%) of these aneurysms ruptured. The absolute risk of rupture after growth was 2.9% (95% CI, 0.9-4.9) at 6 months, 4.3%(95% CI, 1.9-6.7) at 1 year, and 6.0% (95% CI, 2.9-9.1) at 2 years. In multivariable analyses, predictors of rupture were size (7mmor larger hazard ratio, 3.1; 95% CI, 1.4-7.2), shape (irregular hazard ratio, 2.9; 95% CI, 1.3-6.5), and site (middle cerebral artery hazard ratio, 3.6; 95% CI, 0.8-16.3; anterior cerebral artery, posterior communicating artery, or posterior circulation hazard ratio, 2.8; 95% CI, 0.6-13.0). In the triple-S (size, site, shape) prediction model, the 1-year risk of rupture ranged from 2.1% to 10.6%.CONCLUSION AND RELEVANCE Within 1 year after growth detection, rupture occurred in approximately 1 of 25 aneurysms. The triple-S risk prediction model can be used to estimate absolute risk of rupture for the initial period after detection of growth. Show less
Despite the large overall beneficial effects of endovascular treatment in patients with acute ischemic stroke, severe disability or death still occurs in almost one-third of patients. These... Show moreDespite the large overall beneficial effects of endovascular treatment in patients with acute ischemic stroke, severe disability or death still occurs in almost one-third of patients. These patients, who might not benefit from treatment, have been previously identified with traditional logistic regression models, which may oversimplify relations between characteristics and outcome, or machine learning techniques, which may be difficult to interpret. We developed and evaluated a novel evolutionary algorithm for fuzzy decision trees to accurately identify patients with poor outcome after endovascular treatment, which was defined as having a modified Rankin Scale score (mRS) higher or equal to 5. The created decision trees have the benefit of being comprehensible, easily interpretable models, making its predictions easy to explain to patients and practitioners. Insights in the reason for the predicted outcome can encourage acceptance and adaptation in practice and help manage expectations after treatment. We compared our proposed method to CART, the benchmark decision tree algorithm, on classification accuracy and interpretability. The fuzzy decision tree significantly outperformed CART: using 5-fold cross-validation with on average 1090 patients in the training set and 273 patients in the test set, the fuzzy decision tree misclassified on average 77 (standard deviation of 7) patients compared to 83 (+/- 7) using CART. The mean number of nodes (decision and leaf nodes) in the fuzzy decision tree was 11 (+/- 2) compared to 26 (+/- 1) for CART decision trees. With an average accuracy of 72% and much fewer nodes than CART, the developed evolutionary algorithm for fuzzy decision trees might be used to gain insights into the predictive value of patient characteristics and can contribute to the development of more accurate medical outcome prediction methods with improved clarity for practitioners and patients. Show less
Lindenholz, A.; Bresser, J. de; Kolk, A.G. van der; Worp, H.B. van der; Witkamp, T.D.; Hendrikse, J.; Schaaf, I.C. van der 2021
The relevance of intracranial vessel wall lesions detected with MRI is not fully established. In this study (trial identification number: NTR2119; ), 7T MRI was used to investigate if a higher... Show moreThe relevance of intracranial vessel wall lesions detected with MRI is not fully established. In this study (trial identification number: NTR2119; ), 7T MRI was used to investigate if a higher vessel wall lesion burden is associated with more cerebral parenchymal changes in patients with ischemic stroke or transient ischemic attack (TIA). MR images of 82 patients were assessed for the number of vessel wall lesions of the large intracranial arteries and for cerebral parenchymal changes, including the presence and number of cortical, small subcortical, and deep gray matter infarcts; lacunes of presumed vascular origin; cortical microinfarcts; and periventricular and deep white matter hyperintensities (WMHs). Regression analyses showed that a higher vessel wall lesion burden was associated with the presence of small subcortical infarcts, lacunes of presumed vascular origin, and deep gray matter infarcts (relative risk 1.18; 95% CI, 1.03-1.35) and presence of moderate-to-severe periventricular WMHs (1.21; 95% CI, 1.03-1.42), which are all manifestations of small vessel disease (SVD). The burden of enhancing vessel wall lesions was associated with the number of cortical microinfarcts only (1.48; 95% CI, 1.04-2.11). These results suggest an interrelationship between large vessel wall lesion burden and cerebral parenchymal manifestations often linked to SVD or, alternatively, that vascular changes occur in both large and small intracranial arteries simultaneously. Show less
Ramos, L.A.; Kappelhof, M.; Os, H.J.A. van; Chalos, V.; Kranendonk, K. van; Kruyt, N.D.; ... ; Marquering, H.A. 2020
Background: Although endovascular treatment (EVT) has greatly improved outcomes in acute ischemic stroke, still one third of patients die or remain severely disabled after stroke. If we could... Show moreBackground: Although endovascular treatment (EVT) has greatly improved outcomes in acute ischemic stroke, still one third of patients die or remain severely disabled after stroke. If we could select patients with poor clinical outcome despite EVT, we could prevent futile treatment, avoid treatment complications, and further improve stroke care. We aimed to determine the accuracy of poor functional outcome prediction, defined as 90-day modified Rankin Scale (mRS) score >= 5, despite EVT treatment.Methods: We included 1,526 patients from the MR CLEAN Registry, a prospective, observational, multicenter registry of ischemic stroke patients treated with EVT. We developed machine learning prediction models using all variables available at baseline before treatment. We optimized the models for both maximizing the area under the curve (AUC), reducing the number of false positives.Results: From 1,526 patients included, 480 (31%) of patients showed poor outcome. The highest AUC was 0.81 for random forest. The highest area under the precision recall curve was 0.69 for the support vector machine. The highest achieved specificity was 95% with a sensitivity of 34% for neural networks, indicating that all models contained false positives in their predictions. From 921 mRS 0-4 patients, 27-61 (3-6%) were incorrectly classified as poor outcome. From 480 poor outcome patients in the registry, 99-163 (21-34%) were correctly identified by the models.Conclusions: All prediction models showed a high AUC. The best-performing models correctly identified 34% of the poor outcome patients at a cost of misclassifying 4% of non-poor outcome patients. Further studies are necessary to determine whether these accuracies are reproducible before implementation in clinical practice. Show less
