Search

Background: Different Circle of Willis (CoW) variants have variable prevalences of aneurysm development, but the hemodynamic variation along the CoW and its relation to presence and size of unruptured intracranial aneurysms (UIAs) are not well known. Purpose: Gain insight into hemodynamic imaging markers of the CoW for UIA development by comparing these outcomes to the corresponding contralateral artery without an UIA using 4D flow magnetic resonance imaging (MRI). Study Type: Retrospective, cross-sectional study. Subjects: Thirty-eight patients with an UIA, whereby 27 were women and a mean age of 62 years old. Field Strength/Sequence: Four-dimensional phase-contrast (PC) MRI with a 3D time-resolved velocity encoded gradient echo sequence at 7 T. Assessment: Hemodynamic parameters (blood flow, velocity pulsatility index [vPI], mean velocity, distensibility, and wall shear stress [peak systolic (WSSMAX), and time-averaged (WSSMEAN)]) in the parent artery of the UIA were compared to the corresponding contralateral artery without an UIA and were related to UIA size. Statistical Tests: Paired t-tests and Pearson Correlation tests. The threshold for statistical significance was P < 0.05 (two-tailed). Results: Blood flow, mean velocity, WSSMAX, and WSSMEAN were significantly higher, while vPI was lower, in the parent artery relative to contralateral artery. The WSSMAX of the parent artery significantly increased linearly while the WSSMEAN decreased linearly with increasing UIA size. Conclusions: Hemodynamic parameters and WSS differ between parent vessels of UIAs and corresponding contralateral vessels. WSS correlates with UIA size, supporting a potential hemodynamic role in aneurysm pathology. Level of Evidence: 2. Technical Efficacy: Stage 2.

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.Methods:We performed a prospective cohort study in patients ≥18 years old with a newly diagnosed UIA in two 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 neurological 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 to baseline (adjusted USER-P decrease one-month post-occlusion: -12.8 (95%CI:-23.8- -1.9). HRQoL and emotional functioning gradually improved after occlusion (EQ-5D increase at one-year: 8.6 (95%CI:0.1-17.0) and HADS decrease at one-year: -5.4 (95%CI:-9.4- -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 one-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.Conclusions:After UIA diagnosis, QoL improves gradually after preventive occlusion and directly after counselling at the outpatient clinic in patients without occlusion, resulting in comparable one-year QoL outcomes. A passive coping style is an important predictor of poor QoL outcomes in all UIA patients.

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 based on easily retrievable patient, aneurysm, and treatment characteristics.Methods:For this multicenter cohort study, we combined individual patient data from unruptured intracranial aneurysm patients ≥18 years undergoing preventive endovascular treatment (standard, balloon-assisted or stent-assisted coiling, Woven EndoBridge-device, or flow-diverting stent) or microneurosurgical clipping at one of 10 participating centers from three continents between 2000-2018. The primary outcome was death from any cause or clinical deterioration from neurological complications ≤30 days. We selected predictors based on previous knowledge about relevant risk factors and predictor performance and studied the association between predictors and complications with logistic regression. We assessed model performance with calibration plots and concordance (c) statistics.Results:Of 1282 included patients, 94 (7.3%) had neurological symptoms that resolved c-statistic was 0.72 (95%CI:0.67-0.77) and the absolute complication risk ranged from 3.2% (95%CI:1.6%-14.9%;≤1 point) to 33.1% (95%CI:25.4%-41.5%;≥6 points). For microneurosurgical treatment (n=530), the c-statistic was 0.72 (95%CI:0.67-0.77) and the complication risk ranged from 4.9% (95%CI:1.5%-14.9%;≤1 point) to 49.9% (95%CI:39.4%-60.6%;≥6 points).Conclusions:The SAFETEA risk scores for endovascular and microneurosurgical treatment are based on seven easily retrievable risk factors to predict the absolute risk of procedural complications in patients with unruptured intracranial aneurysms. The scores need external validation before the predicted risks can be properly used to support decision making in clinical practice.

Background Intracranial atherosclerosis is an important cause of ischemic stroke and is associated with several vascular risk factors. Current imaging is mainly based on the assessment of luminal narrowing rather than abnormalities in the vessel wall. Purpose To investigate the relationship between vascular risk factors and atherosclerotic lesion burden of intracranial arteries assessed with vessel wall MRI at 7 T in participants with ischemic stroke or transient ischemic attack (TIA). Materials and Methods In this prospective study (trial identification number: NTR2119; www.trialregister.nl), study participants who presented with ischemic stroke or TIA of the anterior circulation between December 2009 and September 2017 underwent pre- and postcontrast 7-T vessel wall MRI within 3 months of symptom onset. All large arteries of the intracranial circulation were assessed for number, location, and enhancement of vessel wall lesions. Generalized estimating equations for Poisson regression were used to investigate the relationship between vascular risk factors and number or enhancement of vessel wall lesions. Results Ninety participants (52 men; mean age, 60 years) were evaluated. Increasing age (relative risk [RR], 1.02; 95% confidence interval [CI]: 1.01, 1.03), hypertension (RR, 1.46; 95% CI: 1.06, 2.02), diabetes mellitus (RR, 1.67; 95% CI: 1.20, 2.33), and a higher multivariable vascular risk score (Second Manifestations of Arterial Disease risk score) (RR, 1.01; 95% CI: 1.00, 1.02) were associated with a higher number of vessel wall lesions in the anterior circulation. Contrast material-enhancing vessel wall lesions were associated only with increasing age (RR, 1.03; 95% CI: 1.01, 1.05). No association was found between smoking and the number of vessel wall lesions. Conclusion Except for smoking, traditional common cardiovascular risk factors were associated with a higher number and enhancement of intracranial vessel wall lesions at 7-T MRI in individuals evaluated after ischemic stroke or transient ischemic attack. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

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).To compare pulsatility, pulsatility attenuation, and distensibility along the ICA between patients with cSVD and controls and to assess the association between iICAC and pulsatility and distensibility.Retrospective, explorative cross-sectional study.A total of 17 patients with cSVD, manifested as lacunar infarcts or deep intracerebral hemorrhage, and 17 age- and sex-matched controls.Three-dimensional (3D) T1-weighted gradient echo imaging and 4D phase-contrast (PC) MRI with a 3D time-resolved velocity encoded gradient echo sequence at 7 T.Blood-flow velocity pulsatility index (vPI) and arterial distensibility were calculated for seven ICA segments (C1-C7). iICAC presence and volume were determined from available brain CT scans (acquired as part of standard clinical care) in patients with cSVD.Independent t-tests and linear mixed models. The threshold for statistically significance was P 0.05 (two tailed).The cSVD group showed significantly higher ICA vPI and significantly lower distensibility compared to controls. Controls showed significant attenuation of vPI over the carotid siphon (-4.9% ± 3.6%). In contrast, patients with cSVD showed no attenuation, but a significant increase of vPI (+6.5% ± 3.1%). iICAC presence and volume correlated positively with vPI (r = 0.578) in patients with cSVD and negatively with distensibility (r = -0.386).Decreased distensibility and reduced pulsatility attenuation are associated with increased iICAC and may contribute to cSVD. Confirmation in a larger prospective study is required.2 TECHNICAL EFFICACY: Stage 2.

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 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 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.

Magnetic resonance imaging (MRI) is considered as the reference standard to assess early joint changes in hemophilia. However, the clinical relevance of MRI findings is still unknown. The aim of this prospective study was to assess the predictive value of MRI for 5-year joint bleeding and progression of arthropathy in patients with hemophilia. Both knees and ankles of patients with hemophilia and absent or limited arthropathy on radiographs were assessed by using MRI and radiographs. MRI scans were scored according to the International Prophylaxis Study Group MRI score for hemophilic arthropathy. Patients were followed up for 5 years, including assessment of joint bleeding and repeated radiographic assessment. Associations between baseline MRI findings with 5-year bleeding and progression of arthropathy were expressed as odds ratios (OR), adjusted for severity of disease and joint bleeding history. Baseline assessment included 104 joints of 26 patients with hemophilia (median age, 21 years). Four ankles with severe joint changes were excluded. Follow-up was available for 96 (92%) of 104 joints. During 5 years of follow-up, bleeding was reported for 36% of joints. Five-year bleeding was significantly increased in joints with synovial hypertrophy at 80% vs 27% in joints without synovial hypertrophy (OR, 10.1; 95% confidence interval, 3.4-31.3). In joints with normal baseline radiographs, any osteochondral or synovial changes on MRI were associated with radiographic changes 5 years later (positive predictive value, 75%; negative predictive value, 98%). Joints with synovial hypertrophy on MRI had a significantly higher chance of 5-year bleeding. All MRI changes, except effusion, were strong predictors for development of arthropathy on radiographs.

The relevance of intracranial vessel wall lesions detected with MRI is not fully established. In this study (trial identification number: NTR2119; www.trialregister.nl), 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.

Item does not contain fulltext 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 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 data were 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 1 mm or greater increase in 1 direction at follow-up imaging. MAIN OUTCOMES AND MEASURES: The primary outcome was 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 (7 mm or 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.

Time-of-Flight Magnetic Resonance Angiographs (TOF-MRAs) enable visualization and analysis of cerebral arteries. This analysis may indicate normal variation of the configuration of the cerebrovascular system or vessel abnormalities, such as aneurysms. A model would be useful to represent normal cerebrovascular structure and variabilities in a healthy population and to differentiate from abnormalities. Current anomaly detection using autoencoding convolutional neural networks usually use a voxelwise mean-error for optimization. We propose optimizing a variational-autoencoder (VAE) with structural similarity loss (SSIM) for TOF-MRA reconstruction. A patch-trained 2D fully-convolutional VAE was optimized for TOF-MRA reconstruction by comparing vessel segmentations of original and reconstructed MRAs. The method was trained and tested on two datasets: the IXI dataset, and a subset from the ADAM challenge. Both trained networks were tested on a dataset including subjects with aneurysms. We compared VAE optimization with L2-loss and SSIM-loss. Performance was evaluated between original and reconstructed MRAs using mean square error, mean-SSIM, peak-signal-to-noise-ratio and dice similarity index (DSI) of segmented vessels. The L2-optimized VAE outperforms SSIM, with improved reconstruction metrics and DSIs for both datasets. Optimization using SSIM performed best for visual image quality, but with discrepancy in quantitative reconstruction and vascular segmentation. The larger, more diverse IXI dataset had overall better performance. Reconstruction metrics, including SSIM, were lower for MRAs including aneurysms. A SSIM-optimized VAE improved the visual perceptive image quality of TOF-MRA reconstructions. A L2-optimized VAE performed best for TOF-MRA reconstruction, where the vascular segmentation is important. SSIM is a potential metric for anomaly detection of MRAs., Comment: SPIE Medical Imaging 2021

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 distensibility over the whole ICA trajectory, including effects of age and sex. Methods and Results We assessed arterial velocity pulsatility and distensibility using flow‐sensitized 2‐dimensional phase‐contrast 3.0 Tesla magnetic resonance imaging in 118 healthy participants. Velocity pulsatility index (vPI=(V max −V min )/V mean ) and arterial distensibility defined as area pulsatility index (A max −A min )/A mean ) were calculated at C1, C3, and C7 segments of the ICA. vPI increased between C1 and C3 (0.85±0.13 versus 0.93±0.13, P P P P P Conclusions Along the whole ICA trajectory, vPI increased from extracranial C1 up to the carotid siphon C3 with overall no effect on vPI between extracranial C1 and intracranial C7 segments. This suggests that the bony carotid canal locally limits the arterial distensibility of the ICA, increasing the vPI at C3 which is consequently decreased again over the carotid siphon. In addition, vPI in men is higher and increases with age.

Introduction Knowledge of risk factors for rebleeding after aneurysmal subarachnoid haemorrhage can help tailoring ultra-early aneurysm treatment. Previous studies have identified aneurysm size and various patient-related risk factors for early (≤24 h) rebleeding, but it remains unknown if aneurysm configuration is also a risk factor. We investigated whether irregular shape, aspect- and bottleneck ratio of the aneurysm are independent risk factors for early rebleeding after aneurysmal subarachnoid haemorrhage. Patients and methods From a prospectively collected institutional database, we investigated data from consecutive aneurysmal subarachnoid haemorrhage patients who were admitted ≤24 h after onset between December 2009 and January 2015. The admission computed tomographic angiogram was used to assess aneurysm size and configuration. With Cox regression, we calculated stepwise-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for irregular shape, aspect ratio ≥1.6 mm and bottleneck ratio ≥1.6 mm. Results Of 409 included patients, 34 (8%) patients had in-hospital rebleeding ≤24 h after ictus. Irregular shape was an independent risk factor for rebleeding (HR: 3.9, 95% CI: 1.3–11.3) after adjustment for age, sex, PAASH score, aneurysm location, aneurysm size and aspect- and bottleneck ratio. Aspect ratio ≥1.6 mm (HR: 2.3, 95% CI: 0.8–6.5) and bottleneck ratio ≥1.6 mm (HR: 1.7, 95% CI: 0.8–3.6) were associated with an increased risk of rebleeding, but were not independent risk factors after multivariable adjustment. Conclusions Irregular shape is an independent risk factor for early rebleeding. However, since the majority of subarachnoid haemorrhage patients have an irregular aneurysm, additional risk factors have to be found for aneurysm treatment prioritisation.

Objectives Recently, hippocampal calcification as observed on brain CT examinations was identified in over 20% of people over 50 years of age and a relation between hippocampal calcification and cognitive decline was shown. We determined the prevalence and investigated the vascular risk factors of hippocampal calcification in patients with cerebrovascular disease. Methods Hippocampal calcification was scored bilaterally on presence and severity on CT examinations in a cohort of 1130 patients with (suspected) acute ischaemic stroke. Multivariable logistic regression analysis, adjusting for age and gender as well as adjusting for multiple cardiovascular disease risk factors, was used to determine risk factors for hippocampal calcification. Results Hippocampal calcification was present in 381 (34%) patients. Prevalence increased with age from 8% below 40 to 45% at 80 years and older. In multivariable logistic regression analysis, age per decile (OR 1.41 [95% CI 1.26–1.57], p < 0.01), hypertension (OR 0.74 [95% CI 0.56–0.99], p = 0.049), diabetes mellitus (OR 1.57 [95% CI 1.10–2.25], p = 0.01) and hyperlipidaemia (OR 1.63 [95% CI 1.20–2.22], p < 0.01) were significantly associated with hippocampal calcification. Conclusions Hippocampal calcification was a frequent finding on CT in this cohort of stroke patients and was independently positively associated with hyperlipidaemia and diabetes mellitus, suggesting an atherosclerotic origin. Key Points • Hippocampal calcification is prevalent in over 30% of cerebrovascular disease patients. • Prevalence increases from 8% below 40 to 45% over 80 years. • Hippocampal calcification is associated with cardiovascular risk factors hyperlipidaemia and diabetes mellitus. Electronic supplementary material The online version of this article (10.1007/s00330-018-5372-8) contains supplementary material, which is available to authorized users.

Background and Purpose— Early prediction of outcome in acute ischemic stroke is important for clinical management. This study aimed to compare the relationship between early follow-up multimodality computed tomographic (CT) imaging and clinical outcome at 90 days in a large multicenter stroke study. Methods— From the DUST study (Dutch Acute Stroke Study), patients were selected with (1) anterior circulation occlusion on CT angiography (CTA) and ischemic deficit on CT perfusion (CTP) on admission, and (2) day 3 follow-up noncontrast CT, CTP, and CTA. Follow-up infarct volume on noncontrast CT, poor recanalization on CTA, and poor reperfusion on CTP (mean transit time index ≤75%) were related to unfavorable outcome after 90 days defined as modified Rankin Scale 3 to 6. Four multivariable models were constructed: (1) only baseline variables (model 1), (2) model 1 with addition of infarct volume, (3) model 1 with addition of recanalization, and (4) model 1 with addition of reperfusion. Area under the curves of the receiver operating characteristic curves of the models were compared using the DeLong test. Results— A total of 242 patients were included. Poor recanalization was found in 21%, poor reperfusion in 37%, and unfavorable outcome in 44%. The area under the curve of the receiver operating characteristic curve without follow-up imaging was 0.81, with follow-up noncontrast CT 0.85 ( P =0.02), CTA 0.86 ( P =0.01), and CTP 0.86 ( P =0.01). All 3 follow-up imaging modalities improved outcome prediction compared with no imaging. There was no difference between the imaging models. Conclusions— Follow-up imaging after 3 days improves outcome prediction compared with prediction based on baseline variables alone. CTA recanalization and CTP reperfusion do not outperform noncontrast CT at this time point. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00880113.

Background Patients with migraine might be more susceptible of spreading depolarizations, which are known to affect vascular and neuronal function and penumbra recovery after stroke. We investigated whether these patients have more severe stroke progression and less favorable outcomes after recanalization therapy. Methods We included patients from a prospective multicenter ischemic stroke cohort. Lifetime migraine history was based on the International Classification of Headache Disorders II criteria. Patients without confirmed migraine diagnosis were excluded. Patients underwent CT angiography and CT perfusion Results We included 600 patients of whom 43 had migraine. There were no differences between patients with or without migraine in presence of a perfusion deficit on admission (aRR: 0.98, 95%CI: 0.77–1.25), infarct core volume (aB: -10.8, 95%CI: -27.04–5.51), penumbra volume (aB: -11.6, 95%CI: -26.52–3.38), mean blood brain barrier permeability (aB: 0.08, 95%CI: -3.11–2.96), malignant edema (0% vs. 5%), hemorrhagic transformation (aRR: 0.26, 95%CI: 0.04–1.73), final infarct volume (aB: -14.8, 95%CI: 29.9–0.2) or outcome after recanalization therapy (mRS > 2, aRR: 0.50, 95%CI: 0.21–1.22). Conclusion Elderly patients with a history of migraine do not seem to have more severe stroke progression and have similar treatment outcomes compared with patients without migraine.

INTRODUCTION: The risk of rebleeding is highest during the initial hours after aneurysmal subarachnoid haemorrhage (aSAH), but the aneurysm is not occluded in all patients immediately after admission. Our aim was to determine the proportion of aSAH patients with poor outcome from early in-hospital rebleeding that can be prevented by three emergency aneurysm occlusion regimes. PATIENTS AND METHODS: From our prospectively collected database, we retrieved from all aSAH patients admitted between July 2007 and July 2017 data on clinical condition on admission, time of rebleeding, and outcome at 3 months. RESULTS: Of 1391 consecutive aSAH patients, 923 were in good clinical condition and had an aneurysm on initial imaging that was amenable for treatment. Poor outcome from rebleeding could have been avoided by treatment

Objective: To investigate sex differences in presence and location of atherosclerosis in a large population of acute ischaemic stroke patients. Methods: Participants were included from the Dutch acute stroke study (DUST), a large prospective multicentre cohort study. All patients received CT/CT-angiography within 9 hours of stroke onset. We assessed the presence of any sign of atherosclerosis in the intra- and extracranial circulation. In addition, we determined the burden of intracranial atherosclerosis by quantifying intracranial internal carotid artery (ICA) calcifications, resulting in calcium volumes. Relative risks between women and men were calculated using multivariable Poisson regression, and adjusted (aRR) for potential confounders (age, hypertension, hyperlipidemia, diabetes, smoking and alcohol use). Results: We included 1397 patients with a mean age of 67 years, of whom 600 (43%) were women. Presence of atherosclerosis in intracranial vessel segments was found as frequently in women as in men (71% versus 72%, aRR 0.95; 95%CI 0.89-1.01). In addition, intracranial ICA calcium volume did not differ between women and men (median volume 124 mm 3 , IQR 35.5-304.5 in women versus 112 mm 3 , IQR 33.0-276.5 in men; tertile largest volume 37% in women versus 33% in men, aRR 1.00; 95% CI 0.95-1.05). Extracranial atherosclerosis was less common in women compared with men (74% vs 81%, aRR 0.86; 95%CI 0.81-0.92). (Table) Conclusions: In patients with acute ischemic stroke the prevalence of intracranial atherosclerosis does not differ between women and men, while extracranial atherosclerosis is less often present in women compared with men.

IMPORTANCE: The risk of procedural clinical complications and the case-fatality rate (CFR) from preventive treatment of unruptured intracranial aneurysms varies between studies and may depend on treatment modality and risk factors. OBJECTIVE: To assess current procedural clinical 30-day complications and the CFR from endovascular treatment (EVT) and neurosurgical treatment (NST) of unruptured intracranial aneurysms and risk factors of clinical complications. DATA SOURCES: We searched PubMed, Excerpta Medica Database, and the Cochrane Database for studies published between January 1, 2011, and January 1, 2017. STUDY SELECTION: Studies reporting on clinical complications, the CFR, and risk factors, including 50 patients or more undergoing EVT or NST for saccular unruptured intracranial aneurysms after January 1, 2000, were eligible. DATA EXTRACTION AND SYNTHESIS: Per treatment modality, we analyzed clinical complication risk and the CFR with mixed-effects logistic regression models for dichotomous data. For studies reporting data on complication risk factors, we obtained risk ratios (RRs) or odds ratios (ORs) with 95% CIs and pooled risk estimates with weighted random-effects models. MAIN OUTCOMES AND MEASURES: Clinical complications within 30 days and the CFR. RESULTS: We included 114 studies (106 433 patients with 108 263 aneurysms). For EVT (74 studies), the pooled clinical complication risk was 4.96% (95% CI, 4.00%-6.12%), and the CFR was 0.30% (95% CI, 0.20%-0.40%). Factors associated with complications from EVT were female sex (pooled OR, 1.06 [95% CI, 1.01-1.11]), diabetes (OR, 1.81 [95% CI, 1.05-3.13]), hyperlipidemia (OR, 1.76 [95% CI, 1.3-2.37]), cardiac comorbidity (OR, 2.27 [95% CI, 1.53-3.37]), wide aneurysm neck (>4 mm or dome-to-neck ratio >1.5; OR, 1.71 [95% CI, 1.38-2.11]), posterior circulation aneurysm (OR, 1.42 [95% CI, 1.15-1.74]), stent-assisted coiling (OR, 1.82 [95% CI, 1.16-2.85]), and stenting (OR, 3.43 [95% CI, 1.45-8.09]). For NST (54 studies), the pooled complication risk was 8.34% (95% CI, 6.25%-11.10%) and the CFR was 0.10% (95% CI, 0.00%-0.20%). Factors associated with complications from NST were age (OR per year increase, 1.02 [95% CI, 1.01-1.02]), female sex (OR, 0.43 [95% CI, 0.32-0.85]), coagulopathy (OR, 2.14 [95% CI, 1.13-4.06]), use of anticoagulation (OR, 6.36 [95% CI, 2.55-15.85]), smoking (OR, 1.95 [95% CI, 1.36-2.79]), hypertension (OR, 1.45 [95% CI, 1.03-2.03]), diabetes (OR, 2.38 [95% CI, 1.54-3.67]), congestive heart failure (OR, 2.71 [95% CI, 1.57-4.69]), posterior aneurysm location (OR, 7.25 [95% CI, 3.70-14.20]), and aneurysm calcification (OR, 2.89 [95% CI, 1.35-6.18]). CONCLUSIONS AND RELEVANCE: This study identifies risk factors for procedural complications. Large data sets with individual patient data are needed to develop and validate prediction scores for absolute complication risks and CFRs from EVT and NST modalities.

Background and aims Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification. Methods Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis. Results In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27–3.44]) and hypertension (OR 2.09 [CI 1.29–3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11–5.14]) and previous vascular disease (OR 2.20 [CI 1.30–3.75]). Conclusions Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology.

PURPOSE: Leptomeningeal collaterals improve outcome in stroke patients. There is great individual variability in their extent. Internal carotid artery (ICA) stenosis may lead to more extensive recruitment of leptomeningeal collaterals. The purpose of this study was to evaluate the association of pre-existing ICA stenosis with leptomeningeal collateral filling visualized with computed tomography perfusion (CTP).METHODS: From a prospective acute ischemic stroke cohort, patients were included with an M1 middle cerebral artery (MCA) occlusion and absent ipsilateral, extracranial ICA occlusion. ICA stenosis was determined on admission CT angiography (CTA). Leptomeningeal collaterals were graded as good (>50%) or poor (≤50%) collateral filling in the affected MCA territory on CTP-derived vessel images of the admission scan. The association between ipsilateral ICA stenosis ≥70% and extent of collateral filling was analyzed using logistic regression. In a multivariable analysis the odds ratio (OR) of ICA stenosis ≥70% was adjusted for complete circle of Willis, gender and age.RESULTS: We included 188 patients in our analyses, 50 (26.6%) patients were classified as having poor collateral filling and 138 (73.4%) as good. Of the patients 4 with poor collateral filling had an ICA stenosis ≥70% and 14 with good collateral filling. Unadjusted and adjusted ORs of ICA stenosis ≥70% for good collateral filling were 1.30 (0.41-4.15) and 2.67 (0.81-8.77), respectively. Patients with poor collateral filling had a significantly worse outcome (90-day modified Rankin scale 3-6; 80% versus 52%, p = 0.001).CONCLUSION: No association was found between pre-existing ICA stenosis and extent of CTP derived collateral filling in patients with an M1 occlusion.

Objectives The radiological Pettersson score (PS) is widely applied for classification of arthropathy to evaluate costly haemophilia treatment. This study aims to assess and improve inter- and intra-observer reliability and agreement of the PS. Methods Two series of X-rays (bilateral elbows, knees, and ankles) of 10 haemophilia patients (120 joints) with haemophilic arthropathy were scored by three observers according to the PS (maximum score 13/joint). Subsequently, (dis-)agreement in scoring was discussed until consensus. Example images were collected in an atlas. Thereafter, second series of 120 joints were scored using the atlas. One observer rescored the second series after three months. Reliability was assessed by intraclass correlation coefficients (ICC), agreement by limits of agreement (LoA). Results Median Pettersson score at joint level (PSjoint) of affected joints was 6 (interquartile range 3–9). Using the consensus atlas, inter-observer reliability of the PSjoint improved significantly from 0.94 (95 % confidence interval (CI) 0.91–0.96) to 0.97 (CI 0.96–0.98). LoA improved from ±1.7 to ±1.1 for the PSjoint. Therefore, true differences in arthropathy were differences in the PSjoint of >2 points. Intra-observer reliability of the PSjoint was 0.98 (CI 0.97–0.98), intra-observer LoA were ±0.9 points. Conclusions Reliability and agreement of the PS improved by using a consensus atlas. Key Points • Reliability of the Pettersson score significantly improved using the consensus atlas. • The presented consensus atlas improved the agreement among observers. • The consensus atlas could be recommended to obtain a reproducible Pettersson score. Electronic supplementary material The online version of this article (doi:10.1007/s00330-015-4013-8) contains supplementary material, which is available to authorized users.

INTRODUCTION: Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT occurs secondary to reperfusion in combination with ischemic BBB injury or is caused by the negative effect of IV-rtPA on BBB integrity. The aim of this study was to establish the association between reperfusion and the occurrence of HT. METHODS: From the DUST study, patients were selected with admission and follow-up non-contrast CT (NCCT) and CT perfusion (CTP) imaging, and a perfusion deficit in the middle cerebral artery territory on admission. Reperfusion was categorized qualitatively as reperfusion or no-reperfusion by visual comparison of admission and follow-up CTP. Occurrence of HT was assessed on follow-up NCCT. The association between reperfusion and occurrence of HT on follow-up was estimated by calculating odds ratios (ORs) and 95 % confidence intervals (CIs) with additional stratification for IV-rtPA treatment. RESULTS: Inclusion criteria were met in 299 patients. There was no significant association between reperfusion and HT (OR 1.2 95%CI 0.5-3.1). In patients treated with IV-rtPA (n = 203), the OR was 1.3 (95%CI 0.4-4.0), and in patients not treated with IV-rtPA (n = 96), the OR was 0.8 (95%CI 0.1-4.5). HT occurred in 14 % of the IV-rtPA patients and in 7 % of patients without IV-rtPA (95%CI of difference -1 to 14 %). CONCLUSION: Our results suggest that the increased risk of HT after acute ischemic stroke treatment is not dependent on the reperfusion status.

PURPOSE: Increased blood-brain barrier permeability (BBBP) can result from ischemia. In this study the relation between stroke severity, patient characteristics and admission BBBP values measured with CT-perfusion (CTP) was investigated in acute ischemic stroke patients. METHODS: From prospective data of the Dutch Acute Stroke Study 149 patients with a middle cerebral artery stroke and extended CTP were selected. BBBP values were measured in the penumbra and infarct core as defined by CTP thresholds, and in the contra-lateral hemisphere. The relation between stroke (severity) variables and patient characteristics, including early CT signs, dense vessel sign (DVS), time to scan and National Institute of Health Stroke Score (NIHSS), and BBBP parameters in penumbra and infarct core was quantified with regression analysis. RESULTS: Early CT signs were related to higher BBBP values in the infarct core (B = 0.710), higher ipsi- to contra-lateral BBBP ratios (B = 0.326) and higher extraction ratios in the infarct core (B = 16.938). Females were found to have lower BBBP values in penumbra and infarct core (B = - 0.446 and - 0.776 respectively) and lower extraction ratios in the infarct core (B = - 10.463). If a DVS was present the ipsi- to contra-lateral BBBP ratios were lower (B = - 0.304). There was no relation between NIHSS or time to scan and BBBP values. CONCLUSION: Early CT signs are related to higher BBBP values in the infarct core, suggesting that only severe ischemic damage alters BBBP within the first hours after symptom onset.

Background Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. Methods We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and ≥2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family’s proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis. Results We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6–3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8–4.3). No association was found for the other three circle of Willis variations. Conclusions In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.

Background and Purpose— Induced hypertension is widely used to treat delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage, but a literature review shows that its presumed effectiveness is based on uncontrolled case-series only. We here report clinical outcome of aneurysmal subarachnoid hemorrhage patients with DCI included in a randomized trial on the effectiveness of induced hypertension. Methods— Aneurysmal subarachnoid hemorrhage patients with clinical symptoms of DCI were randomized to induced hypertension or no induced hypertension. Risk ratios for poor outcome (modified Rankin Scale score >3) at 3 months, with 95% confidence intervals, were calculated and adjusted for age, clinical condition at admission and at time of DCI, and amount of blood on initial computed tomographic scan with Poisson regression analysis. Results— The trial aiming to include 240 patients was ended, based on lack of effect on cerebral perfusion and slow recruitment, when 21 patients had been randomized to induced hypertension, and 20 patients to no hypertension. With induced hypertension, the adjusted risk ratio for poor outcome was 1.0 (95% confidence interval, 0.6–1.8) and the risk ratio for serious adverse events 2.1 (95% confidence interval, 0.9–5.0). Conclusions— Before this trial, the effectiveness of induced hypertension for DCI in aneurysmal subarachnoid hemorrhage patients was unknown because current literature consists only of uncontrolled case series. The results from our premature halted trial do not add any evidence to support induced hypertension and show that this treatment can lead to serious adverse events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01613235.

Introduction: Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. Methods: From a prospectively collected series of aSAH patients admitted between 2007–2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. Results: Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. Conclusion: Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose.

Background Perimesencephalic hemorrhage (PMH) is a type of subarachnoid hemorrhage with excellent long-term outcomes. Only 1 well-documented case of in-hospital rebleeding after PMH is described in the literature, which occurred after initiating antithrombotic treatment because of myocardial ischemia. We describe a patient with PMH without antithrombotic treatment who had 2 episodes of recurrent bleeding on the day of ictus. To validate the radiologic findings, we conducted a case-control study. Six neuroradiologists and 2 neuroradiology fellows performed a blinded assessment of serial unenhanced head computed tomography (CT) scans of 8 patients with a perimesencephalic bleeding pattern (1 index patient, 6 patients with PMH, 1 patient with perimesencephalic bleeding pattern and basilar artery aneurysm) to investigate a potential increase in amount of subarachnoid blood. Case Description A 56-year-old woman with a perimesencephalic bleeding pattern and negative CT angiography had 2 episodes after the onset headache with a sudden increase of the headache. Blinded assessment of serial head CT scans of 8 patients with a perimesencephalic bleeding pattern identified the patient who was clinically suspected to have 2 episodes of recurrent bleeding to have an increased amount of subarachnoid blood on 2 subsequent CT scans. Conclusions Recurrent bleeding after PMH may also occur in patients not treated with antithrombotics. Even after early rebleeding, the prognosis of PMH is excellent.

INTRODUCTION: Clinical reasoning in diagnostic imaging professions is a complex skill that requires processing of visual information and image manipulation skills. We developed a digital simulation-based test method to increase authenticity of image interpretation skill assessment. METHODS: A digital application, allowing volumetric image viewing and manipulation, was used for three test administrations of the national Dutch Radiology Progress Test for residents. This study describes the development and implementation process in three phases. To assess authenticity of the digital tests, perceived image quality and correspondence to clinical practice were evaluated and compared with previous paper-based tests (PTs). Quantitative and qualitative evaluation results were used to improve subsequent tests. RESULTS: Authenticity of the first digital test was not rated higher than the PTs. Test characteristics and environmental conditions, such as image manipulation options and ambient lighting, were optimized based on participants' comments. After adjustments in the third digital test, participants favored the image quality and clinical correspondence of the digital image questions over paper-based image questions. CONCLUSIONS: Digital simulations can increase authenticity of diagnostic radiology assessments compared with paper-based testing. However, authenticity does not necessarily increase with higher fidelity. It can be challenging to simulate the image interpretation task of clinical practice in a large-scale assessment setting, because of technological limitations. Optimizing image manipulation options, the level of ambient light, time limits, and question types can help improve authenticity of simulation-based radiology assessments.

Background and Purpose— Migraine is a well-established risk factor for ischemic stroke, but migraine is also related to other vascular diseases. This study aims to investigate the association between migraine and cerebrovascular atherosclerosis in patients with acute ischemic stroke. Methods— We retrieved data on patients with ischemic stroke from the DUST (Dutch Acute Stroke Study). Migraine history was assessed with a migraine screener and confirmed by telephone interview based on the ICHD criteria (International Classification of Headache Disorders). We assessed intra- and extracranial atherosclerotic changes and quantified intracranial internal carotid artery calcifications as measure of atherosclerotic burden on noncontrast computed tomography and computed tomographic angiography. We calculated risk ratios with adjustments for possible confounders with multivariable Poisson regression analyses. Results— We included 656 patients, aged 18 to 99 years, of whom 53 had a history of migraine (29 with aura). Patients with migraine did not have more frequent atherosclerotic changes in intracranial (51% versus 74%; adjusted risk ratio, 0.82; 95% confidence interval, 0.64–1.05) or extracranial vessels (62% versus 79%; adjusted risk ratio, 0.93; 95% confidence interval, 0.77–1.12) than patients without migraine and had comparable internal carotid artery calcification volumes (largest versus medium and smallest volume tertile, 23% versus 35%; adjusted risk ratio, 0.93; 95% confidence interval, 0.57–1.52). Conclusions— Migraine is not associated with excess atherosclerosis in large vessels in patients with acute ischemic stroke. Our findings suggest that the biological mechanisms by which migraine results in ischemic stroke are not related to macrovascular cerebral atherosclerosis.