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Background: Radiologically isolated syndrome (RIS) is typified by multiple sclerosis (MS)-like lesions on imaging, without clinical MS symptoms. The prevalence of pediatric RIS is largely unknown. Objective: The objective of the study is to provide an estimated RIS prevalence in a population-based cohort of children. Methods: We used data from the Generation R study to identify the childhood RIS prevalence. Results: In 5238 participants, only one RIS case was identified (prevalence: 0.02%; 95% confidence interval (CI): 0.00–0.11). During a 62-month follow-up, imaging examinations showed accrual of new focal demyelinating lesions; however, no clinical MS symptoms occurred. Conclusions: This study shows that the occurrence of RIS in children from the general population is rare.

BACKGROUND AND PURPOSE: Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up. MATERIALS AND METHODS: We included symptomatic patients with a carotid stenosis of ,70% who underwent MDCTA and MR imaging at baseline (n=180). MDCTA was repeated at 2 years (n=73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis. RESULTS: At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR = 12.1; 95% CI, 3.5-42.0), higher relative lipid-rich necrotic core (OR= 1.7; 95% CI, 1.3-2.2), higher relative intraplaque hemorrhage volume (OR= 1.7; 95% CI, 1.3-2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7-6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm3 [IQR, 0.97-1.16 cm3] versus 0.86 cm3 [IQR, 0.73-1.00 cm3]; P=.029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13-31%] versus 2% [IQR, 0-14%]; P=.002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8-24%] versus 0% [IQR, 0-5%]; P<.001). CONCLUSIONS: Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

OBJECTIVE: To evaluate the role of blood pressure (BP) as mediator of the effect of conscious sedation (CS) compared to local anesthesia (LA) on functional outcome after endovascular treatment (EVT). METHODS: Patients treated in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry centers with CS or LA as preferred anesthetic approach during EVT for ischemic stroke were analyzed. First, we evaluated the effect of CS on area under the threshold (AUT), relative difference between baseline and lowest procedural mean arterial pressure (∆LMAP), and procedural BP trend, compared to LA. Second, we assessed the association between BP and functional outcome (modified Rankin Scale [mRS]) with multivariable regression. Lastly, we evaluated whether BP explained the effect of CS on mRS. RESULTS: In 440 patients with available BP data, patients treated under CS (n = 262) had larger AUTs (median 228 vs 23 mm Hg*min), larger ∆LMAP (median 16% vs 6%), and a more negative BP trend (-0.22 vs -0.08 mm Hg/min) compared to LA (n = 178). Larger ∆LMAP and AUTs were associated with worse mRS (adjusted common odds ratio [acOR] per 10% drop 0.87, 95% confidence interval [CI] 0.78-0.97, and acOR per 300 mm Hg*min 0.89, 95% CI 0.82-0.97). Patients treated under CS had worse mRS compared to LA (acOR 0.59, 95% CI 0.40-0.87) and this association remained when adjusting for ∆LMAP and AUT (acOR 0.62, 95% CI 0.42-0.92). CONCLUSIONS: Large BP drops are associated with worse functional outcome. However, BP drops do not explain the worse outcomes in the CS group.

Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. Key Points: • Data-driven processes like radiomics risk false discoveries due to high-dimensionality

The aim of this study was to evaluate and present an automated method for registration of magnetic resonance imaging (MRI) and computed tomography (CT) or cone beam CT (CBCT) images of the mandibular region for patients with oral squamous cell carcinoma (OSCC). Registered MRI and (CB)CT could facilitate the three-dimensional virtual planning of surgical guides employed for resection and reconstruction in patients with OSCC with mandibular invasion. MRI and (CB)CT images were collected retrospectively from 19 patients. MRI images were aligned with (CB)CT images employing a rigid registration approach (stage 1), a rigid registration approach using a mandibular mask (stage 2), and two non-rigid registration approaches (stage 3). Registration accuracy was quantified by the mean target registration error (mTRE), calculated over a set of landmarks annotated by two observers. Stage 2 achieved the best registration result, with an mTRE of 2.5 ± 0.7 mm, which was comparable to the inter- and intra-observer variabilities of landmark placement in MRI. Stage 2 was significantly better aligned compared to all approaches in stage 3. In conclusion, this study demonstrated that rigid registration with the use of a mask is an appropriate image registration method for aligning MRI and (CB)CT images of the mandibular region in patients with OSCC.

Background: Radiologically isolated syndrome (RIS) is typified by multiple sclerosis (MS)-like lesions on imaging, without clinical MS symptoms. The prevalence of pediatric RIS is largely unknown. Objective: The objective of the study is to provide an estimated RIS prevalence in a population-based cohort of children. Methods: We used data from the Generation R study to identify the childhood RIS prevalence. Results: In 5238 participants, only one RIS case was identified (prevalence: 0.02%; 95% confidence interval (CI): 0.00–0.11). During a 62-month follow-up, imaging examinations showed accrual of new focal demyelinating lesions; however, no clinical MS symptoms occurred. Conclusions: This study shows that the occurrence of RIS in children from the general population is rare.

Objective The disconnectivity hypothesis postulates that partial loss of connecting white matter fibers between brain regions contributes to the development of dementia. Using diffusion MRI to quantify global and tract-specific white matter microstructural integrity, we tested this hypothesis in a longitudinal population-based study. Methods Global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were obtained in 4,415 people without dementia (mean age 63.9 years, 55.0% women) from the prospective population-based Rotterdam Study with brain MRI between 2005 and 2011. We modeled the association of these diffusion measures with risk of dementia (follow-up until 2016) and with changes on repeated cognitive assessment after on average 5.4 years, adjusting for age, sex, education, macrostructural MRI markers, depressive symptoms, cardiovascular risk factors, and APOE genotype. Results During a median follow-up of 6.8 years, 101 participants had incident dementia, of whom 83 had clinical Alzheimer disease (AD). Lower global values of FA and higher values of MD were associated with an increased risk of dementia (adjusted hazard ratio [95% confidence interval (CI)] per SD increase for MD 1.79 [1.44–2.23] and FA 0.65 [0.52–0.80]). Similarly, lower global values of FA and higher values of MD related to more cognitive decline in people without dementia (difference in global cognition per SD increase in MD [95% CI] was −0.04 [−0.07 to −0.01]). Associations were most profound in the projection, association, and limbic system tracts. Conclusions Structural disconnectivity is associated with an increased risk of dementia and more pronounced cognitive decline in the general population.

Background: The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. Methods: A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. Results: EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. Conclusion: One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs.

Introduction: Vascular remodeling is a compensatory enlargement of the vessel wall in response to atherosclerotic plaque growth. We aimed to investigate the association between intraplaque hemorrhage (IPH), vascular remodeling, and luminal dimensions in recently symptomatic patients with mild to moderate carotid artery stenosis in which the differences in plaque size were taken into account. Materials and Methods: We assessed vessel dimensions on MRI of the symptomatic carotid artery in 164 patients from the Plaque At RISK study. This study

OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed genom

Introduction and Aim: Hemorrhagic transformation (HT) frequently occurs after acute ischemic stroke and negatively influences the functional outcome. Usually, HT is classified by its radiological appearance. Discriminating between the subtypes can be complicated, and interobserver variation is considerable. Therefore, we aim to quantify rather than classify hemorrhage volumes and determine the association of hemorrhage volume with functional outcome in comparison with the European Cooperative Acute Stroke Study II classification. Patients and Methods: We included patients from the MR CLEAN trial with follow-up imaging. Hemorrhage volume was estimated by manual delineation of the lesion, and HT was classified according to the European Cooperative Acute Stroke Study II classification [petechial hemorrhagic infarction types 1 (HI1) and 2 (HI2) and parenchymal hematoma types 1 (PH1) and 2 (PH2)] on follow-up CT 24 h to 2 weeks after treatment. We assessed functional outcome using the modified Rankin Scale 90 days after stroke onset. Ordinal logistic regression with and without adjustment for potential confounders was used to describe the association of hemorrhage volume with functional outcome. We created regression models including and excluding total lesion volume as a confounder. Results: We included 478 patients. Of these patients, 222 had HT. Median hemorrhage volume was 3.37 ml (0.80–12.6) and per HT subgroup; HI1: 0.2 (0.0–1.7), HI2: 3.2 (1.7–6.1), PH1: 6.3 (4.2–13), and PH2: 47 (19–101). Hemorrhage volume was associated with functional outcome [adjusted common odds ratio (acOR): 0.83, 95% CI: 0.73–0.95] but not anymore after adjustment for total lesion volume (acOR: 0.99, 95% CI: 0.86–1.15, per 10 ml). Hemorrhage volume in patients with PH2 was significantly associated with functional outcome after adjusting total lesion volume (acOR: 0.70, 95% CI: 0.50–0.98). Conclusion: HT volume is associated with functional outcomes in patients with acute ischemic stroke but

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 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.

Purpose: In ASPECTS, 10 brain regions are scored visually for presence of acute ischemic stroke damage. We evaluated automated ASPECTS in comparison to expert readers. Methods: Consecutive, baseline non-contrast CT-scans (5-mm slice thickness) from the prospective MR CLEAN trial (n = 459, MR CLEAN Netherlands Trial Registry number: NTR1804) were evaluated. A two-observer consensus for ASPECTS regions (normal/abnormal) was used as reference standard for training and testing (0.2/0.8 division). Two other observers provided individual ASPECTS-region scores. The Automated ASPECTS software was applied. A region score specificity of ≥ 90% was used to determine the software threshold for detection of an affected region based on relative density difference between affected and contralateral region. Sensitivity, specificity, and receiver-operating characteristic curves were calculated. Additionally, we assessed intraclass correlation coefficients (ICCs) for automated ASPECTS and observers in comparison to the reference standard in the test set. Results: In the training set (n = 104), with software thresholds for a specificity of ≥ 90%, we found a sensitivity of 33–49% and an area under the curve (AUC) of 0.741–0.785 for detection of an affected ASPECTS region. In the test set (n = 355), the results for the found software thresholds were 89–89% (specificity), 41–57% (sensitivity), and 0.750–0.795 (AUC). Comparison of automated ASPECTS with the reference standard resulted in an ICC of 0.526. Comparison of observers with the reference standard resulted in an ICC of 0.383–0.464. Conclusion: The performance of automated ASPECTS is comparable to expert readers and could support readers in the detection of early ischemic changes.

Purpose: To optimize the diffusion-weighting b values and postprocessing pipeline for hybrid intravoxel incoherent motion diffusion kurtosis imaging in the head and neck region. Methods: Optimized diffusion-weighting b value sets ranging between 5 and 30 b values were constructed by optimizing the Cramér-Rao lower bound of the hybrid intravoxel incoherent motion diffusion kurtosis imaging model. With this model, the perfusion fraction, pseudodiffusion coefficient, diffusion coefficient, and kurtosis were estimated. Sixteen volunteers were scanned with a reference b value set and 3 repeats of the optimized sets, of which 1 with volunteers swallowing on purpose. The effects of (1) b value optimi

Introduction: Our aim was to study whether systemic metabolites are associated with magnetic resonance imaging (MRI) measures of brain and hippocampal atrophy and white matter hyperintensities (WMH). Methods: We studied associations of 143 plasma-based metabolites with MRI measures of brain and hippocampal atrophy and WMH in three independent cohorts (n = 3962). We meta-analyzed the results of linear regression analyses to determine the association of metabolites with MRI measures. Results: Higher glucose levels and lower levels of three small high density lipoprotein (HDL) particles were associated with brain atrophy. Higher glucose levels were associated with WMH. Discussion: Glucose levels were associated with brain atrophy and WMH, and small HDL particle levels were associated with brain atrophy. Circulating metabolites may aid in developing future intervention trials.

Background: Antiplatelet therapy may increase the risk of symptomatic intracranial hemorrhage after endovascular treatment for ischemic stroke but may also have a beneficial effect on functional outcome. The aim of this study is to compare safety and efficacy outcomes after endovascular treatment in patients with and without prior antiplatelet therapy. Methods: We analyzed patients registered in the MR CLEAN Registry between March 2014 and November 2017, for whom data on antiplatelet therapy were available. We used propensity score nearest-neighbor matching with replacement to balance the probability of receiving prior antiplatelet therapy between the prior antiplatelet therapy and no prior antiplatelet therapy group and adjusted for baseline prognostic factors to compare these groups. Primary outcome was symptomatic intracranial hemorrhage. Secondary outcomes were 90-day functional outcome (modified Rankin Scale), successful reperfusion (extended thrombolysis in cerebral infarction score ≥2B) and 90-day mortality. Results: Thirty percent (n = 937) of the 3154 patients were on prior antiplatelet therapy, who were matched to 477 patients not on prior antiplatelet therapy. Symptomatic intracranial hemorrhage occurred in 74/937 (7.9%) patients on prior antiplatelet therapy and in 27/477 (5.6%) patients without prior antiplatelet therapy adjusted odds ratio 1.47, 95% confidence interval 0.86–2.49. No associations were found between prior antiplatelet therapy and functional outcome (adjusted common odds ratio 0.87, 95% confidence interval 0.65–1.16), successful reperfusion (adjusted odds ratio 1.23, 95% confidence interval 0.77–1.97), or 90-day mortality (adjusted odds ratio 1.15, 95% confidence interval 0.86–1.54). Conclusion: We found no evidence of an association of prior antiplatelet therapy with the risk of symptomatic intracranial hemorrhage after endovascular treatment, nor on functional outcome, reperfusion, or mortality. A substantial beneficial or detrimental e

Introduction: Literature on prevalence of symptomatic internal carotid artery stenosis is scarce and heterogeneous. Prevalence may have decreased in recent years due to improved management of cardiovascular risk factors. We aim to estimate current prevalence and identify risk factors of ipsilateral internal carotid artery stenosis in patients with recent hemispheric transient ischaemic attack or ischa

Normal brain-aging occurs at all structural levels. Excessive pathophysiological changes in the brain, beyond the normal one, are implicated in the etiology of brain disorders such as severe forms of the schizophrenia spectrum and dementia. To account for brain-aging in health and disease, it is critical to study the age-dependent trajectories of brain biomarkers at various levels and among different age groups. The intracranial volume (ICV) is a key biological marker, and changes in the ICV during the lifespan can teach us about the biology of development, aging, and gene X environment interactions. However, whether ICV changes with age in adulthood is not resolved. Applying a semi-automatic in-house-built algorithm for ICV extraction on T1w MR brain scans in the Dutch longitudinal cohort (GROUP), we measured ICV changes. Individuals between the ages of 16 and 55 years were scanned up to three consecutive times with 3.320.32 years between consecutive scans (N ¼ 482, 359, 302). Using the extracted ICVs, we calculated ICV longitudinal aging-trajectories based on three analysis methods; direct calculation of ICV differences between the first and the last scan, fitting all ICV measurements of individuals to a straight line, and applying a global linear mixed model fitting. We report statistically significant increase in the ICV in adulthood until the fourth decade of life (average change þ0.03%/y, or about 0.5 ml/y, at age 20), and decrease in the ICV afte

Background Adiposity is associated with larger left ventricular mass in children and adults. The role of body fat distribution in these associations is not clear. We examined the

The aim of this study was to develop a convolutional neural network (CNN) that automatically detects and segments intra-arterial thrombi on baseline non-contrast computed tomography (NCCT) scans. We retrospectively collected computed tomography (CT)-scans of patients with an anterior circulation large vessel occlusion (LVO) from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands trial, both for training (n = 86) and validation (n = 43). For testing we included patients with (n = 58) and without (n = 45) an LVO from our comprehensive stroke center. Ground truth was established by consensus between two experts using both CT angiography and NCCT. We evaluated the CNN for correct identification of a thrombus, its location and thrombus segmentation and compared these with the results of a neurologist in training and expert neuroradiologist. Sensitivity of the CNN thrombus detection was 0.86, vs. 0.95 and 0.79 for the neuroradiologists. Specificity was 0.65 for the network vs. 0.58 and 0.82 for the neuroradiologists. The CNN correctly identified the location of the thrombus in 79% of the cases, compared to 81% and 77% for the neuroradiologists. The sensitivity and specificity for thrombus identification and the rate for correct thrombus location assessment by the CNN were similar to those of expert neuroradiologists.

BACKGROUND: Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributabl

Background: Atrial fibrillation is an important risk factor for ischemic stroke, and is associated with an increased risk of poor outcome after ischemic stroke. Endovascular thrombectomy is safe and effective in acute ischemic stroke patients with large vessel occlusion of the anterior circulation. This meta-analysis aims to investigate whether there is an interaction between atrial fibrillation and treatment effect of endovascular thrombectomy, and secondarily whether atrial fibrillation is associated with worse outcome in patients with ischemic stroke due to large vessel occlusion. Methods: Individual patient data were from six of the recent randomised clinical trials (MR CLEAN, EXTEND-IA, REVASCAT, SWIFT PRIME, ESCAPE, PISTE) in which endovascular thrombectomy plus standard care was compared to standard care alone. Primary outcome measure was the shift on the modified Rankin scale (mRS) at 90 days. Secondary outcomes were functional independence (mRS 0–2) at 90 days, National Institutes of Health Stroke Scale score at 24 h, symptomatic intracranial hemorrhage and mortality at 90 days. The primary effect parameter was the adjusted common odds ratio, estimated with ordinal logistic regression (shift analysis); treatment effect modification of atrial fibrillation was assessed with a multiplicative interaction term. Results: Among 1351 patients, 447 pa

Objectives: Intrathecal drug delivery is used for the treatment of intractable spasticity, dystonia, and pain. When the symptomatology fails to respond to therapy, the cause could be failure of the medication infusion. The purpose of this study is to assess pump catheter access port (CAP)-myelography and CAP-CT-myelography as advanced imaging methods in treatment failure. Materials and Methods: We analyzed observational routinely collected data of 70 CAP procedures with 2D/3D reconstructions and additional imaging of 53 adult patients where the cause of treatment was unclear between November 2013 and November 2018. CAP-myelography and CAP-CT myelography were performed with postprocessing 2D/3D reconstructions. When myelography could not be obtained or when the result did not reveal the cause of the treatment failure, additional procedures, such as noncontrast CT, MRI, lumbar puncture CT, and 111Indium-DTPA SPECT-CT, were performed. Results: CAP fluid aspiration prior to contrast medium injection was not possible (N = 17). In one case, contrast was injected into the pump pocket unintentionally (N = 1). Of 70 procedures, 24% were unaspiratable. The remaining CAP myelography examinations (N = 52) had limited value for the diagnosis. CAP-CT myelography (N = 50) was normal (N = 31). The abnormal results (N = 19) were dorsal dural leak (N = 5), subdural catheter position (N = 2), limited rostral flow of contrast material (N = 4), limited and abnormal contrast distribution (N = 3), obstruction of rostral flow (N = 2), a leak at the pump-catheter connection (N = 1), and a sheared catheter localized in the pump pocket (N = 2). Limited contrast distributions were found to be false positive findings (N = 2). Four normal CT-CAP myelographic procedures were false negatives, as the reference tests revealed a cause of intrathecal drug delivery (ITDD) failure. The CAP-CT procedures resulted in a sensitivity of 81% (17/21) and a specificity of 93% (27/29). Conclusions: CAP-CT myelog

Background: The Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading. Aims: We present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology. Methods: We included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0–2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors. Results: In total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58–88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome. Conclusion: qTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score.

Background and Purpose- The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods- We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results- In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22-2.32) to respectively 1.36 (95% CI, 0.97-1.91) and 1.24 (95% CI, 0.87-1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions- The NIHSS within 1 week satisfies the requir

Background: To investigate the association between fasting serum insulin and glucose levels with atherosclerotic plaque composition in the carotid artery. Impaired insulin and glucose levels are implicated in the etiology of cardiovascular disease; however, their influence on the formation and composition of atherosclerotic plaque

Background and purpose: Infarct volume is a valuable outcome measure in treatment trials of acute ischemic stroke and is strongly associated with functional outcome. Its manual volumetric assessment is, however, too demanding to be implemented in clinical practice. Objective: To assess the value of convolutional neural networks (CNNs) in the automatic segmentation of infarct volume in follow-up CT images in a large population of patients with acute ischemic stroke. Materials and methods: We included CT images of 1026 patients from a large pooling of patients with acute ischemic stroke. A reference standard for the infarct segmentation was generated by manual delineation. We introduce three CNN models for the segmentatio

Background and aims: COPD is associated with an increased risk of cardiovascular morbidity and mortality, potentially by mechanisms of atherosclerosis. Insight into location-specific vulnerability to atherosclerosis in COPD, including intracranial arteries, is lacking. We aimed to investigate the relation between COPD and atherosclerosis in multiple vessel beds within a large population-based cohort study. Methods: From 2003 to 2006, a random sample of 2187 elderly participants (mean age, 69.6 ± 6.8 years; 50.9% female; 11.7% COPD) from the population-based Rotterdam Study underwent computed tomography to quantify atherosclerotic coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial carotid artery calcification (ECAC), and intracranial carotid artery calcification (ICAC). We investigated the association of COPD [ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) < 70%] with the presence of calcification and with calcification volumes in each vessel bed using logistic and linear regression, with adjustments for cardiovascular risk factors including smoking. Results: The prevalence of CAC, AAC and ECAC was significantly higher in subjects with COPD compared to those without. After adjusting for age and smoking, COPD remained associated with the presence of ECAC (odds ratio 1.46 [95% confidence interval, 1.02–2.07, p = 0.037]). COPD was significantly associated with larger calcification volumes in all four vessel beds in people in whom calcification was present. Conclusions: The results of this study suggest that COPD plays a role in extracranial carotid artery atherosclerosis initiation and systemic atherosclerosis aggravation.

Objectives: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. Design: A cross-sectional study. Participants: 200 women aged >45 with PCOS, and 200 age-matched controls. Measurements: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. Results: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P <.001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P <.001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. Conclusions: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long

Objectives This study explored group-wise quantitative measures of tract-specific white matter (WM) microstructure and functional default mode network (DMN) connectivity to establish an initial indication of their clinical applicability for early-stage and follow-up differential diagnosis of Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD). Methods Eleven AD and 12 bvFTD early-stage patients and 18 controls underwent diffusion tensor imaging and resting state functional magnetic resonance imaging at 3 T. All AD and 6 bvFTD patients underwent the same protocol at 1-year follow-up. Functional connectivity measures of DMN and WM tract-specific diffusivity measures were determined for all groups. Exploratory analyses were performed to compare all measures between the three groups at baseline and between patients at follow-up. Additionally, the difference between baseline and follow-up diffusivity measures in AD and bvFTD patients was compared. Results Functional connectivity of the DMN was not different between groups at baseline and at follow-up. Diffusion abnormalities were observed widely in bvFTD and regionally in the hippocampal cingulum in AD. The extent of the differences between bvFTD and AD was diminished at follow-up, yet abnormalities were still more pronounced in bvFTD. The rate of change was similar in bvFTD and AD. Conclusions This study provides a tentative indication that quantitative tract-specific microstructural WM abnormalities, but not quantitative functional connectivity of the DMN, may aid early-stage and follow-up differential diagnosis of bvFTD and AD. Specifically, pronounced microstructural changes in anterior WM tracts may characterise bvFTD, whereas microstructural abnormalities of the hippocampal cingulum may characterise AD.

Phenocopy frontotemporal dementia (phFTD) shares core characteristics with behavioral variant frontotemporal dementia (bvFTD), yet without associated cognitive deficits and brain abnormalities on conventional magnetic resonance imaging (MRI), and without progression. Using advanced MRI techniques, we previously observed subtle structural and functional brain changes in phFTD similar to bvFTD. The aim of the current study was to follow these as well as cognition in phFTD over time, by means of a descriptive case series. Cognition, gray matter (GM) volume and white matter (WM) microstructure, and perfusion of 6 phFTD patients were qualitatively compared longitudinally (3-years follow-up), and cross-sectionally with baseline data from 9 bvFTD patients and 17 controls. For functional brain changes, arterial spin labeling (ASL) was performed to assess GM perfusion. For structural brain changes, diffusion tensor imaging was performed to assess WM microstructure and T1w imaging to assess GM volume. MRI acquisition was performed at 3T (General Electric, US). Clinical profiles of phFTD cases at follow-up are described. At follow-up phFTD patients showed clinical symptomatology similar to bvFTD, but had a relatively stable clinical profile. Longitudinal qualitative comparisons in phFTD showed some deterioration of language and memory function, a stable pattern of structural brain abnormalities and increased perfusion over time. Additionally, both baseline and follow-up cognitive scores and structural values in phFTD were generally in between those of controls and bvFTD. Although a descriptive case series does not allow for strong conclusions, these observations in a unique longitudinal phFTD patient cohort are suggestive of the notion that phFTD and bvFTD may belong to the same disease spectrum. They may also provide a basis for further longitudinal studies in phFTD, specifically exploring the structural vs. functional brain changes. Such studies are essential for improved in

Background-—The purpose of this study was to investigate the association between kidney function and arterial calcification in major vascular beds and to establish whether arterial calcification mediates the relation between kidney function measures and cardiovascular disease (CVD) incidence. Methods and Results-—In 2241 participants from the Rotterdam Study (mean age 69 years, 52% female), kidney function was assessed using the estimated glomerular filtration rate and urine albumin-to-creatinine ratio. All participants underwent noncontrast computed tomography to quantify the amount of arterial calcification in the coronary arteries, aortic arch, extracranial, and intracranial internal carotid arteries. We used linear regression models, adjusted for age, sex, and cardiovascular risk factors, to evaluate the association between kidney function and arterial calcification volume in the 4 vessel beds. Incidence rate of CVD was calculated in 3 groups of participants based on their kidney function and presence of arterial calcification. We conducted mediation analysis to evaluate whether arterial calcification mediates this association. We found that in age- and sex-adjusted models, lower estimated glomerular filtration rate and higher albumin-to-creatinine ratio were associated with larger calcification volumes in all 4 vascular beds. Adjusting for cardiovascular risk factors attenuated the effect estimates. CVD incidence was higher in participants with estimated glomerular filtration rate <60 mL/min per 1.73 m2 and presence of arterial calcification compared with individuals with estimated glomerular filtration rate >60 and no calcification. After adjusting for cardiovascular risk factors, arterial calcification did not mediate the association between kidney function measures and CVD incidence. Conclusions-—The association of impaired kidney function and larger volumes of arterial calcification is partly explained by cardiovascular risk factors. Arterial calcification

Background: Actinomycetes can rarely cause intracranial infection and may cause a variety of complications. We describe a fatal case of intracranial and intra-orbital actinomycosis of odontogenic origin with a unique presentation and route of dissemination. Also, we provide a review of the current literature. Case presentation: A 58-year-old man presented with diplopia and progressive pain behind his left eye. Six weeks earlier he had undergone a dental extraction, followed by clindamycin treatment for a presumed maxillary infection. The diplopia responded to steroids but recurred after cessation. The diplopia was thought to result from myositis of the left medial rectus muscle, possibly related to a defect in the lamina papyracea. During exploration there was no abnormal tissue for biopsy. The medial wall was reconstructed and the myositis responded again to steroids. Within weeks a myositis on the right side occurred, with CT evidence of muscle swelling. Several months later he presented with right hemiparesis and dysarthria. Despite treatment the patient deteriorated, developed extensive intracranial hemorrhage, and died. Autopsy showed bacterial aggregates suggestive of actinomycotic meningoencephalitis with septic thromboembolism. Retrospectively, imaging studies showed abnormalities in the left infratemporal fossa and skull base and bilateral cavernous sinus. Conclusions: In conclusion, intracranial actinomycosis is difficult to diagnose, with potentially fatal outcome. An accurate diagnosis can often only be established by means of histology and biopsy should be performed whenever feasible. This is the first report of actinomycotic orbital involvement of odontogenic origin, presenting initially as bilateral orbital myositis rather than as orbital abscess. Infection from the upper left jaw extended to the left infratemporal fossa, skull base and meninges and subsequently to the cavernous sinus and the orbits.

Wall shear stress (WSS), the frictional force exerted on endothelial cells by blood flow, is hypothesised to influence atherosclerotic plaque growth and composition. We developed a methodology for image registration of MR and histology images of advanced human carotid plaques and corresponding WSS data, obtained by MRI and computational fluid dynamics. The image registration method requires four types of input images, in vivo MRI, ex vivo MRI, photographs of transversally sectioned plaque tissue and histology images. These images are transformed to a shared 3D image domain by applying a combination of rigid and non-rigid registration algorithms. Transformation matrices obtained from registration of these images are used to transform subject-specific WSS data to the shared 3D image domain as well. WSS values originating from the 3D WSS map are visualised in 2D on the corresponding lumen locations in the histological sections and divided into eight radial segments. In each radial segment, the correlation between WSS values and plaque composition based on histological parameters can be assessed. The registration method was successfully applied to two carotid endarterectomy specimens. The resulting matched contours from the imaging modalities had Hausdorff distances between 0.57 and 0.70 mm, which is in the order of magnitude of the in vivo MRI resolution. We simulated the effect of a mismatch in the rigid registration of imaging modalities on WSS results by relocating the WSS data with respect to the stack of histology images. A 0.6 mm relocation altered the mean WSS values projected on radial bins on average by 0.59 Pa, compared to the output of original registration. This mismatch of one image slice did not change the correlation between WSS and plaque thickness. In conclusion, we created a method to invest

Objects: We describe five traumatic spinal cord injury (SCI) patients with an intrathecal baclofen administration (ITB) failure caused by a rostral CSF flow obstruction referred to our expert center between January 2014 and January 2019. We discuss the diagnostic workup, rostral CSF flow obstruction as the cause of the ITB failure and treatment. Methods: When we could not determine the cause of the ITB failure through the patient’s history, physical spasticity examination, pump readout, absence of fluid in the pump reservoir during aspiration, or plain radiography, we performed pump catheter access port (computed tomography [CT]) myelography. When CT myelography did not reveal the diagnosis, we used scintigraphy. In an obstruction, we aimed for CSF flow restoration. In three cases, we conducted a laminectomy with microsurgical adhesiolysis. In two of these patients, we could not achieve CSF flow restoration; thus, we placed an intradural catheter bypass. Recently, in three patients, we applied a less invasive technique of percutaneous fenestration of the obstruction. Results: In one case, we performed a successful catheter replacement. In another case using surgical adhesiolysis, spasticity control was complete. In two cases, we could obtain improvement with an additional intradural bypass, followed by a percutaneous fenestration of the obstruction, resulting in further improved CSF flow restoration. In one case, percutaneous fenestration was the first line of treatment. In all cases with percutaneous fenestration, we experienced spasticity control. Conclusion: Preliminary results showed that the restoration of rostral CSF flow might result in an effective ITB treatment in patients with an intrathecal obstruction.

Background An adverse fetal environment leads to fetal hemodynamic adaptations with cardiac flow alterations that may subsequently affect cardiac development. We examined the associations of third trimester placental and fetal cardiac hemodynamics with cardiac outcomes in school-age children. Methods and Results We performed a population-based prospective cohort study among 547 mothers and their children. At a gestational age of 30.4 (95% range 28.4-32.7) weeks, we measured umbilical and cerebral artery resistance, cardiac output, and tricuspid and mitral E/A waves with Doppler. At the median age of 10.0 years (95% range 9.4-11.7) we measured cardiac outcomes with cardiac magnetic resonance imaging. Cardiac outcomes included right ventricular end-diastolic volume) and right ventricular ejection fraction, left ventricular end diastolic volume and left ventricular ejection fraction, left ventricular mass, an

Background and Purpose— Predicting malignant middle cerebral artery (MCA) infarction can help to identify patients who may benefit from preventive decompressive surgery. We aimed to investigate the association between the ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) and malignant MCA infarction. Methods— Patients with an occlusion proximal to the M3 segment of the MCA were selected from the DUST (Dutch Acute Stroke Study). Admission imaging included noncontrast computed tomography (CT), CT perfusion, and CT angiography. Patient characteristics and CT findings were collected. The ratio of intracranial CSF volume to ICV (CSF/ICV) was quantified on admission thin-slice noncontrast CT. Malignant MCA infarction was defined as a midline shift of >5 mm on follow-up noncontrast CT, which was performed 3 days after the stroke or in case of clinical deterioration. To test the association between CSF/ICV and malignant MCA infarction, odds ratios and 95% CIs were calculated for 3 multivariable models by using binary logistic regression. Model performances were compared by using the likelihood ratio test. Results— Of the 286 included patients, 35 (12%) developed malignant MCA infarction. CSF/ICV was independently associated with malignant MCA infarction in 3 multivariable models: (1) with age and admission National Institutes of Health Stroke Scale (odds ratio, 3.3; 95% CI, 1.1–11.1), (2) with admission National Institutes of Health Stroke Scale and poor collateral score (odds ratio, 7.0; 95% CI, 2.6–21.3), and (3) with terminal internal carotid artery or proximal M1 occlusion and poor collateral score (odds ratio, 7.7; 95% CI, 2.8–23.9). The performance of model 1 (areas under the receiver operating characteristic curves, 0.795 versus 0.824; P=0.033), model 2 (areas under the receiver operating characteristic curves, 0.813 versus 0.850; P<0.001), and model 3 (areas under the receiver operating characteristic curves, 0.811 versus 0.856; P<0

Background It is unclear whether intravenous thrombolysis ( IVT ) with alteplase before endovascular treatment ( EVT ) is beneficial for patients with acute ischemic stroke caused by a large vessel occlusion. We compared clinical and procedural outcomes, safety, and workflow between patients treated with both IVT and EVT and those treated with EVT alone in routine clinical practice. Methods and Results Using multivariable regression, we evaluated the association of IVT + EVT with 90-day functional outcome (modified Rankin Scale), mortality, reperfusion, first-pass effect, and symptomatic intracranial hemorrhage in the MR CLEAN (Multicenter Randomised Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) Registry. Of 1485 patients, 1161 (78%) were treated with IVT + EVT , and 324 (22%) with EVT alone. Patients treated with IVT + EVT had atrial fibrillation less often (16% versus 44%) and had better pre-stroke modified Rankin Scale scores (pre-stroke modified Rankin Scale 0: 73% versus 52%) than those treated with EVT alone. Procedure time was shorter in the IVT + EVT group (median 62 versus 68 minutes). Nontransferred IVT + EVT patients had longer door-to-groin-puncture times (median 105 versus 94 minutes). IVT + EVT was associated with better functional outcome (adjusted common odds ratio 1.47; 95% CI : 1.10-1.96) and lower mortality (adjusted odds ratio 0.58; 95% CI : 0.40-0.82). Successful reperfusion, first-pass effect, and symptomatic intracranial hemorrhage did not differ between groups. Conclusions In this observational study, patients treated with IVT + EVT had better clinical outcomes than patients who received EVT alone. This finding may demonstrat

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or

Background and Purpose- It is unclear whether endovascular treatment (EVT) is beneficial for patients with acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery. We aimed to compare functional outcomes, technical aspects, and complications of EVT between patients with acute ischemic stroke because of M2 and M1 occlusions in clinical practice. Furthermore, outcome and complications after EVT in dominant and nondominant caliber M2 division occlusions were studied. Methods- Data were obtained from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) which is an ongoing observational study in 16 Dutch centers performing EVT in the Netherlands. Functional outcome was measured with the modified Rankin Scale score at 90 days. Neurological recovery (delta National Institutes of Health Stroke Scale), successful reperfusion rates (extended Thrombolysis in Cerebral Infarction ≥2B), and safety outcomes were also investigated. Associations between occlusion location and outcome were analyzed with ordinal logistic regression models, with adjustment for other prognostic factors. Results- In total, 244 (24%) patients with an M2 and 759 (76%) patients with an M1 occlusion who underwent EVT were analyzed. Functional outcomes were not significantly different between patients with M2 versus M1 occlusions (adjusted common odds ratio, 1.24; 95% CI, 0.87-1.73). Occurrence of symptomatic intracerebral hemorrhage was also similar for M2 and M1 occlusions (6.6% versus 5.9%; P=0.84). Further analysis about dominance of an M2 branch was performed in 175 (72%) patients. Neurological recovery was comparable (mean delta National Institutes of Health Stroke Scale, -2±10 for dominant M2, -5±5 for nondominant M2, and -4±9 [ P=0.24] for M1 occlusions). Furthermore, the effect of reperfusion status on functional outcome was comparable between occlusion divisions (common odds ratio, 1.27; 95%

Introduction: The efficacy of both intravenous treatment (IVT) and endovascular treatment (EVT) for patients with acute ischaemic stroke strongly declines over time. Only a subset of patients with ischaemic stroke caused by an intracranial large vessel occlusion (LVO) in the anterior circulation can benefit from EVT. Several prehospital stroke scales were developed to identify patients that are likely to have an LVO, which could allow for direct transportation of EVT eligible patients to an endovascular-capable centre without delaying IVT for the other patients. We aim to prospectively validate these prehospital stroke scales simultaneously to assess their accuracy in predicting LVO in the prehospital setting. Methods and analysis: Prehospital triage of patients with suspected stroke symptoms (PRESTO) is a prospective multicentre observational cohort study in the southwest of the Netherlands including adult patients with suspected stroke in the ambulance. The paramedic will assess a combination of items from five prehospital stroke scales, without changing the normal workflow. Primary outcome is the clinical diagnosis of an acute ischaemic stroke with an intracranial LVO in the anterior circulation. Additional hospital data concerning the diagnosis and provided treatment will be collected by chart review. Logistic regression analysis will be performed, and performance of the prehospital stroke scales will be expressed as sensitivity, specificity and area under the receiver operator curve. Ethics and dissemination: The Institutional Review Board of the Erasmus MC University Medical Centre has reviewed the study protocol and confirmed that the Dutch Medical Research Involving Human Subjects Act (WMO) is not applicable. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations. The best performing scale, or the simplest scale in case of clinical equipoise, will be integrated in a decision model with other cli

Background and Purpose— Direct transportation to a center with facilities for endovascular treatment might be beneficial for patients with acute ischemic stroke, but it can also cause harm by delay of intravenous treatment. Our aim was to determine the optimal prehospital transportation strategy for individual patients and to assess which factors influence this decision. Methods— We constructed a decision tree model to compare outcome of ischemic stroke patients after transportation to a primary stroke center versus a more distant intervention center. The optimal strategy was estimated based on individual patient characteristics, geographic location, and workflow times. In the base case scenario, the primary stroke center was located at 20 minutes and the intervention center at 45 minutes. Additional sensitivity analyses included an urban scenario (10 versus 20 minutes) and a rural scenario (30 versus 90 minutes). Results— Direct transportation to the intervention center led to better outcomes in the base case scenario when the likelihood of a large vessel occlusion as a cause of the ischemic stroke was >33%. With a high likelihood of large vessel occlusion (66%, comparable with a Rapid Arterial Occlusion Evaluation score of 5 or above), the benefit of direct transportation to the intervention center was 0.10 quality-adjusted life years (=36 days in full health). In the urban scenario, direct transportation to an intervention center was beneficial when the risk of large vessel occlusion was 24% or higher. In the rural scenario, this threshold was 49%. Other factors influencing the decision included door-to-needle times, door-to-groin times, and the door-in-door-out time. Conclusions— The preferred prehospital transportation strategy for suspected stroke patients depends mainly on the likelihood of large vessel occlusion, driving times, and in-hospital workflow times. We constructed a robust model that combines these characteristics and can be used to personalize pre

Structural brain markers are studied extensively in the field of neurodegeneration, but are thought to occur rather late in the process. Functional measures such as functional connectivity are gaining interest as potentially more subtle markers of neurodegeneration. However, brain structure and function are also affected by ‘normal’ brain ageing. More information is needed on how functional connectivity relates to aging, particularly in the absence of overt neurodegenerative disease. We investigated the association of age with resting-state functional connectivity in 2878 non-demented persons between 50 and 95 years of age (54.1% women) from the population-based Rotterdam Study. We obtained nine well-known resting state networks using data-driven methodology. Within the anterior default mode network, ventral attention network, and sensorimotor network, functional connectivity was significantly lower with older age. In contrast, functional connectivity was higher with older age within the visual network. Between resting state networks, we found patterns of both increases and decreases in connectivity in approximate equal proportions. Our results reinforce the notion that the aging brain undergoes a reorganization process, and serves as a solid basis for exploring functional connectivity as a preclinical marker of neurodegenerative disease.

Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO. Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24–48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO. Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (resp. mean −5 vs. mean −1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (−4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00). Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparabl

Background and Purpose-Thrombus characteristics and collateral score are associated with functional outcome in patients with acute ischemic stroke. It has been suggested that they affect each other. The aim of this study is to evaluate the association between clot burden score, thrombus perviousness, and collateral score and to determine whether collateral score influences the association of thrombus characteristics with functional outcome. Methods-Patients with baseline thin-slice noncontrast computed tomography and computed tomographic angiography images from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands) were included (n=195). Collateral score and clot burden scores were determined on baseline computed tomographic angiography. Thrombus attenuation increase was determined by comparing thrombus density on noncontrast computed tomography and computed tomographic angiography using a semiautomated method. The association of collateral score with clot burden score and thrombus attenuation increase was evaluated with linear regression. Mediation and effect modification analyses were used to assess the influence of collateral score on the association of clot burden score and thrombus attenuation increase with functional outcome. Results-A higher clot burden score (B=0.063; 95% confidence interval, 0.008-0.118) and a higher thrombus attenuation increase (B=0.014; 95% confidence interval, 0.003-0.026) were associated with higher collateral score. Collateral score mediated the association of clot burden score with functional outcome. The association between thrombus attenuation increase and functional outcome was modified by the collateral score, and this association was stronger in patients with moderate and good collaterals. Conclusions-Patients with lower thrombus burden and higher thrombus perviousness scores had higher collateral score. The positive effect of thrombus perviousness on clin

Background and Purpose- Previous studies suggest that intracranial carotid artery calcification (ICAC) volume might influence the clinical outcome of patients after endovascular treatment (EVT) for acute ischemic stroke. Importantly, ICAC can be subtyped into a medial or intimal pattern that may differentially influence the effect of EVT in patients with acute ischemic stroke. Methods- All 500 patients included in the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular treatment for acute ischemic stroke in the Netherlands) were evaluated. Volume (mm3) and location pattern (tunica intima or tunica media) of ICAC could be determined on baseline noncontrast computed tomography in 344 patients. Functional outcome at 90 days was assessed with the modified Rankin Scale. Next, we investigated the association of ICAC volume and pattern with functional outcome using adjusted ordinal logistic regression models. Effect modification by EVT was assessed with an interaction term between treatment allocation and ICAC aspect. Results- We found evidence for treatment effect modification by ICAC pattern ( P interaction=0.04). Patients with predominantly medial calcification had better functional outcome with EVT than without this treatment (adjusted common odds ratio, 2.32; 95% CI, 1.23-4.39), but we observed no effect of EVT in patients with predominantly intimal calcifications (adjusted common odds ratio, 0.82; 95% CI, 0.40-1.68). We did not find an association of ICAC volume with functional outcome (adjusted common odds ratio per unit increase ICAC volume 1.01 (95% CI, 0.89-1.13). Moreover, we found no evidence for effect modification by ICAC volume ( P interaction=0.61). Conclusions- The benefit of EVT in acute ischemic stroke patients with a medial calcification pattern is larger than the benefit in patients with an intimal calcification pattern. Clinical Trial Registration- URL: http://www.trialregister.nl . Unique identifier: NTR1804. URL: http://www.isrctn.com .

Background Up to two-thirds of patients are either dependent or dead 3 €months after thrombectomy for acute ischemic stroke (AIS). Loss of cerebral autoregulation may render patients with AIS vulnerable to decreases in mean arterial pressure (MAP). Objective To determine whether a fall in MAP during intervention under general anesthesia (GA) affects funct

Background and Purpose-The utility-weighted modifed Rankin Scale (UW-mRS) has been proposed as a new patientcentered primary outcome in stroke trials. We aimed to describe utility weights for the mRS health states and to evaluate the statistical effciency of the UW-mRS to detect treatment effects in stroke intervention trials. Methods-We used data of the 500 patients enrolled in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Utility values were elicited from the EuroQol Group 5-Dimension Self-Report Questionnaire assessed at 90 days after inclusion, simultaneously with the mRS. Utility weights were determined by averaging the utilities of all patients within each mRS category. We performed simulations to evaluate statistical effciency. The simulated treatment effect was an odds ratio of 1.65 in favor of the treatment arm, similar for all mRS cutoffs. This treatment effect was analyzed using 3 approaches: linear regression with the UW-mRS as outcome, binary logistic regression with a dichotomized mRS (0-1/2-6, 0-2/3-6, and 0-4/5-6), and proportional odds logistic regression with the ordinal mRS. The statistical power of the 3 approaches was expressed as the proportion of 10 000 simulations that resulted in a statistically signifcant treatment effect (P=0.05). Results-The mean utility values (SD) for mRS categories 0 to 6 were: 0.95 (0.08), 0.93 (0.13), 0.83 (0.21), 0.62 (0.27), 0.42 (0.28), 0.11 (0.28), and 0 (0), respectively, but varied substantially between individual patients within each category. The UW-mRS approach was more effcient than the dichotomous approach (power 85% versus 71%) but less effcient than the ordinal approach (power 85% versus 87%). Conclusions-The UW-mRS as primary outcome does not capture individual variation in utility values and may reduce the statistical power of a randomized trial.