Assessment of collateral status by dynamic ct angiography in acute mca stroke: Timing of acquisition and relationship with final infarct volume

BACKGROUND AND PURPOSE: Dynamic CTA is a promising technique for visualization of collateral filling in patients with acute ischemic stroke. Our aim was to describe collateral filling with dynamic CTA and assess the relationship with infarct volume at follow-up. MATERIALS AND METHODS: We selected patients with acute ischemic stroke due to proximal MCA occlusion. Patients underwent NCCT, single-phase CTA, and whole-brain CT perfusion/dynamic CTA within 9 hours after stroke onset. For each patient, a detailed assessment of the extent and velocity of arterial filling was obtained. Poor radiologic outcome was defined as an infarct volume of\70 mL. The association between collateral score and follow-up infarct volume was analyzed with Poisson regression. RESULTS: Sixty-one patients with a mean age of 67 years were included. For all patients combined, the interval that contained the peak of arterial filling in both hemispheres was between 11 and 21 seconds after ICA contrast entry. Poor collateral status as assessed with dynamic CTA was more strongly associated with infarct volume of 70 mL (risk ratio, 1.9; 95% CI, 1.3-2.9) than with single-phase CTA (risk ratio, 1.4; 95% CI, 0.8-2.5). Four subgroups (good-versus-poor and fast-versus-sl

A replication study of genetic risk loci for ischemic stroke in a Dutch population: A case-control study

We aimed to replicate reported associations of 10 SNPs at eight distinct loci with overall ischemic stroke (IS) and its subtypes in an independent cohort of Dutch IS patients. We included 1,375 IS patients enrolled in a prospective multicenter hospital-based cohort in the Netherlands, and 1,533 population-level controls of Dutch descent. We tested these SNPs for association with overall IS and its subtypes (large artery atherosclerosis, small vessel disease and cardioembolic stroke (CE), as classified by TOAST) using an additive multivariable logistic regression model, adjusting for age and sex. We obtained odds ratios (OR) with 95% confidence intervals (95% CI) for the risk allele of each SNP analyzed and exact p-values by permutation. We confirmed the association at 4q25 (PITX2) (OR 1.43; 95% CI, 1.13-1.81, p = 0.029) and 16q22 (ZFHX3) (OR 1.62; 95% CI, 1.26-2.07, p = 0.001) as risk loci for CE. Locus 16q22 was also associated with overall IS (OR 1.24; 95% CI, 1.08-1.42, p = 0.016). Other loci previously associated with IS and/or its subtypes were not confirmed. In conclusion, we validated two loci (4q25, 16q22) associated with CE. In addition, our study may suggest that the association of locus 16q22 may not be limited to CE, but also includes overall IS

CT angiography and CT perfusion improve prediction of infarct volume in patients with anterior circulation stroke

Introduction: We investigated whether baseline CT angiography (CTA) and CT perfusion (CTP) in acute ischemic stroke could improve prediction of infarct presence and infarct volume on follow-up imaging. Methods: We analyzed 906 patients with suspected anterior circulation stroke from the prospective multicenter Dutch acute stroke study (DUST). All patients underwent baseline non-contrast CT, CTA, and CTP and follow-up non-contrast CT/MRI after 3 days. Multivariable regression models were developed including patient characteristics and non-contrast CT, and subsequently, CTA and CTP measures were added. The increase in area under the curve (AUC) and R2 was assessed to determine the additional value of CTA and CTP. Results: At follow-up, 612 patients (67.5 %) had a detectable infarct on CT/MRI; median infarct volume was 14.8 mL (interquartile range (IQR) 2.8–69.6). Regarding infarct presence, the AUC of 0.82 (95 % confidence interval (CI) 0.79–0.85) for patient characteristics and non-contrast CT was improved with addition of CTA measures (AUC 0.85 (95 % CI 0.82–0.87); p < 0.001) and was even higher after addition of CTP measures (AUC 0.89 (95 % CI 0.87–0.91); p < 0.001) and combined CTA/CTP measures (AUC 0.89 (95 % CI 0.87–0.91); p < 0.001). For infarct volume, adding combined CTA/CTP measures (R2 = 0.58) was superior to patient characteristics and non-contrast CT alone (R2 = 0.44) and to addition of CTA alone (R2 = 0.55) or CTP alone (R2 = 0.54; all p < 0.001). Conclusion: In the acute stage, CTA and CTP have additional value over patient characteristics and non-contrast CT for predicting infarct presence and infarct volume on follow-up imaging. These findings could be applied for patient selection in future trials on ischemic stroke treatment

Prediction of outcome in patients with suspected acute ischaemic stroke with CT perfusion and CT angiography: The Dutch acute stroke trial (DUST) study protocol

Background: Prediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated.Methods/design: The DUST is a prospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0-2 represents good outcome, and a score of 3-6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests.Discussion: This study will provide insight in the added prognosti

Cold extremities in migraine: a marker for vascular dysfunction in women

Background and purpose: Migraine is recognized as a vascular risk factor, especially in women. Presumably, migraine, stroke and cardiovascular events share pathophysiological mechanisms. Self-reported cold extremities were investigated as a marker for vascular dysfunction in migraine. Secondly, it was hypothesized that suffering from cold extremities affects sleep quality, possibly exacerbating migraine attack frequency. Methods: In this case–control study, a random sample of 1084 migraine patients and 348 controls (aged 22–65 years) from the LUMINA migraine cohort were asked to complete questionnaires concerning cold extremities, sleep quality and migraine. Results: A total of 594 migraine patients and 199 controls completed the questionnaires. In women, thermal discomfort and cold extremities (TDCE) were more often reported by migraineurs versus controls (odds ratio 2.3, 95% confidence interval 1.4–3.7; P < 0.001), but not significantly so in men (odds ratio 2.5, 95% confidence interval 0.9–6.9; P = 0.09). There was no difference in TDCE comparing migraine with or without aura. Female migraineurs who reported TDCE had higher attack frequencies compared to female migraineurs without TDCE (4 vs. 3 attacks per month; P = 0.003). The association between TDCE and attack frequency was mediated by the presence of difficulty initiating sleep (P = 0.02). Conclusion: Women with migraine more often reported cold extremities compared with controls, possibly indicating a sex-specific vascular vulnerability. Female migraineurs with cold extremities had higher attack frequencies, partly resulting from sleep disturbances. Future studies need to demonstrate whether cold extremities in female migraineurs are a predictor for cardiovascular and cerebrovascular events

No relation between body temperature and arterial recanalization at three days in patients with acute ischaemic stroke

Background: Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. Methods: We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1°Celsius increase in admission body temperature and recanalization at three days. Results: Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1°Celsius, 0.99; 95% confidence interval, 0.94-1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. Conclusions: Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase

Temporal profile of body temperature in acute ischemic stroke: Relation to infarct size and outcome

Background: High body temperatures after ischemic stroke have been associated with larger infarct size, but the temporal profile of this relation is unknown. We assess the relation between temporal profile of body temperature and infarct size and functional outcome in patients with acute ischemic stroke. Methods: In 419 patients with acute ischemic stroke we assessed the relation between body temperature on admission and during the first 3 days with both infarct size and functional outcome. Infarct size was measured in milliliters on CT or MRI after 3 days. Poor functional outcome was defined as a modified Rankin Scale score ≥3 at 3 months. Results: Body temperature on admission was not associated with infarct size or poor outcome in adjusted analyses. By contrast, each additional 1.0 °C in body temperature on day 1 was associated with 0.31 ml larger infarct size (95% confidence interval (CI) 0.04-0.59), on day 2 with 1.13 ml larger infarct size(95% CI, 0.83-1.43), and on day 3 with 0.80 ml larger infarct size (95% CI, 0.48-1.12), in adjusted linear regression analyses. Higher peak body temperatures on days two and three were also associated with poor outcome (adjusted relative risks per additional 1.0 °C in body temperature, 1.52 (95% CI, 1.17-1.99) and 1.47 (95% CI, 1.22-1.77), respectively). Conclusions: Higher peak body temperatures during the first days after ischemic stroke, rather than on admission, are associated with larger infarct size and poor functional outcome. This suggests that prevention of high temperatures may improve outcome if continued for at least 3 days

Distribution of Cardioembolic Stroke: A Cohort Study

Background: A cardiac origin in ischemic stroke is more frequent than previously assumed, but it is not clear which patients benefit from cardiac work-up if obvious cardiac pathology is absent. We hypothesized that thromboembolic stroke with a cardiac source occurs more frequently in the posterior circulation compared with thromboembolic stroke of another etiology. Methods: We performed a multicenter observational study in 3,311 consecutive patients with ischemic stroke who were enrolled in an ongoing prospective stroke registry of 8 University hospitals between September 2009 and November 2014 in The Netherlands. In thi

Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)