Marianne A. A. van Walderveen

Can Arterial Spin Labeling Detect White Matter Perfusion Signal

Since the invention of arterial spin labeling (ASL) it has been acknowledged that ASL does not allow reliable detection of a white matter (WM) perfusion signal. However, recent developments such as pseudo‐continuous labeling and background suppression have improved the quality. The goal of this research was to study the ability of these newer ASL sequences to detect WM perfusion signal. Background suppressed pseudo‐continuous ASL was implemented at 3T with multislice 2D readout after 1525 ms. In five volunteers it was shown that 10 min scanning resulted in significant perfusion signal in 70% of WM voxels. Increasing the labeling and delay time did not lead to a higher percentage. In 27 normal volunteers it was found that 35 averages are necessary to detect significant WM signal, but 150 averages are needed to detect signal in the deep WM. Finally, it was shown in a patient with a cerebral arteriovenous malformation that pseudo‐continuous ASL enabled the depiction of hypointense WM perfusion signal, although dynamic susceptibility contrast MRI showed that this region was merely showing delayed arrival of contrast agent than hypoperfusion. It can be concluded that, except within the deep WM, ASL is sensitive enough to detect WM perfusion signal and perfusion deficits. Magn Reson Med, 2009.

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial

IMPORTANCE Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. DESIGN, SETTING, AND PARTICIPANTS The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. MAIN OUTCOMES AND MEASURES Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. RESULTS Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. CONCLUSION AND RELEVANCE For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion. TRIAL REGISTRATION trialregister.nl Identifier: NTR1804.

Collateral Status on Baseline Computed Tomographic Angiography and Intra-Arterial Treatment Effect in Patients with Proximal Anterior Circulation Stroke

Background and Purpose— Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods— MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. Results— We found a significant modification of treatment effect by collaterals (P=0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7–6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0–2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7–2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1–8.7] for patients with absent collaterals (grade 0). Conclusions— In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. Clinical Trial Registration— URL: http://www.trialregister.nl and http://www.controlled-trials.com. Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.

PHASES Score for Prediction of Intracranial Aneurysm Growth

Background and Purpose— Growth of an intracranial aneurysm occurs in around 10% of patients at 2-year follow-up imaging and may be associated with aneurysm rupture. We investigated whether PHASES, a score providing absolute risks of aneurysm rupture based on 6 easily retrievable risk factors, also predicts aneurysm growth. Methods— In a multicenter cohort of patients with unruptured intracranial aneurysms and follow-up imaging with computed tomography angiography or magnetic resonance angiography, we performed univariable and multivariable Cox regression analyses for the predictors of the PHASES score at baseline, with aneurysm growth as outcome. We calculated hazard ratios and corresponding 95% confidence intervals (CI), with the PHASES score as continuous variable and after division into quartiles. Results— We included 557 patients with 734 unruptured aneurysms. Eighty-nine (12%) aneurysms in 87 patients showed growth during a median follow-up of 2.7 patient-years (range 0.5–10.8). Per point increase in PHASES score, hazard ratio for aneurysm growth was 1.32 (95% CI, 1.22–1.43). With the lowest quartile of the PHASES score (0–1) as reference, hazard ratios were for the second (PHASES 2–3) 1.07 (95% CI, 0.49–2.32), the third (PHASES 4) 2.29 (95% CI, 1.05–4.95), and the fourth quartile (PHASES 5–14) 2.85 (95% CI, 1.43–5.67). Conclusions— Higher PHASES scores were associated with an increased risk of aneurysm growth. Because higher PHASES scores also predict aneurysm rupture, our findings suggest that aneurysm growth can be used as surrogate outcome measure of aneurysm rupture in follow-up studies on risk prediction or interventions aimed to reduce the risk of rupture.

Value of Computed Tomographic Perfusion–Based Patient Selection for Intra-Arterial Acute Ischemic Stroke Treatment

Background and Purpose— The utility of computed tomographic perfusion (CTP)–based patient selection for intra-arterial treatment of acute ischemic stroke has not been proven in randomized trials and requires further study in a cohort that was not selected based on CTP. Our objective was to study the relationship between CTP-derived parameters and outcome and treatment effect in patients with acute ischemic stroke because of a proximal intracranial arterial occlusion. Methods— We included 175 patients who underwent CTP in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN). Association of CTP-derived parameters (ischemic-core volume, penumbra volume, and percentage ischemic core) with outcome was estimated with multivariable ordinal logistic regression as an adjusted odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale. Interaction between CTP-derived parameters and treatment effect was determined using multivariable ordinal logistic regression. Interaction with treatment effect was also tested for mismatch (core <70 mL; penumbra core >1.2; penumbra core >10 mL). Results— The adjusted odds ratio for improved functional outcome for ischemic core, percentage ischemic core, and penumbra were 0.79 per 10 mL (95% confidence interval: 0.71–0.89; P<0.001), 0.82 per 10% (95% confidence interval: 0.66–0.90; P=0.002), and 0.97 per 10 mL (96% confidence interval: 0.92–1.01; P=0.15), respectively. No significant interaction between any of the CTP-derived parameters and treatment effect was observed. We observed no significant interaction between mismatch and treatment effect. Conclusions— CTP seems useful for predicting functional outcome, but cannot reliably identify patients who will not benefit from intra-arterial therapy.

The Prognostic Value of CT Angiography and CT Perfusion in Acute Ischemic Stroke.

Background: CT angiography (CTA) and CT perfusion (CTP) are important diagnostic tools in acute ischemic stroke. We investigated the prognostic value of CTA and CTP for clinical outcome and determined whether they have additional prognostic value over patient characteristics and non-contrast CT (NCCT). Methods: We included 1,374 patients with suspected acute ischemic stroke in the prospective multicenter Dutch acute stroke study. Sixty percent of the cohort was used for deriving the predictors and the remaining 40% for validating them. We calculated the predictive values of CTA and CTP predictors for poor clinical outcome (modified Rankin Scale score 3-6). Associations between CTA and CTP predictors and poor clinical outcome were assessed with odds ratios (OR). Multivariable logistic regression models were developed based on patient characteristics and NCCT predictors, and subsequently CTA and CTP predictors were added. The increase in area under the curve (AUC) value was determined to assess the additional prognostic value of CTA and CTP. Model validation was performed by assessing discrimination and calibration. Results: Poor outcome occurred in 501 patients (36.5%). Each of the evaluated CTA measures strongly predicted outcome in univariable analyses: the positive predictive value (PPV) was 59% for Alberta Stroke Program Early CT Score (ASPECTS) ≤7 on CTA source images (OR 3.3; 95% CI 2.3-4.8), 63% for presence of a proximal intracranial occlusion (OR 5.1; 95% CI 3.7-7.1), 66% for poor leptomeningeal collaterals (OR 4.3; 95% CI 2.8-6.6), and 58% for a >70% carotid or vertebrobasilar stenosis/occlusion (OR 3.2; 95% CI 2.2-4.6). The same applied to the CTP measures, as the PPVs were 65% for ASPECTS ≤7 on cerebral blood volume maps (OR 5.1; 95% CI 3.7-7.2) and 53% for ASPECTS ≤7 on mean transit time maps (OR 3.9; 95% CI 2.9-5.3). The prognostic model based on patient characteristics and NCCT measures was highly predictive for poor clinical outcome (AUC 0.84; 95% CI 0.81-0.86). Adding CTA and CTP predictors to this model did not improve the predictive value (AUC 0.85; 95% CI 0.83-0.88). In the validation cohort, the AUC values were 0.78 (95% CI 0.73-0.82) and 0.79 (95% CI 0.75-0.83), respectively. Calibration of the models was satisfactory. Conclusions: In patients with suspected acute ischemic stroke, admission CTA and CTP parameters are strong predictors of poor outcome and can be used to predict long-term clinical outcome. In multivariable prediction models, however, their additional prognostic value over patient characteristics and NCCT is limited in an unselected stroke population.

Impact of Collateral Status Evaluated by Dynamic Computed Tomographic Angiography on Clinical Outcome in Patients With Ischemic Stroke

Background and Purpose— Status of collateral circulation is a strong predictor of outcome after acute ischemic stroke. Our aim was to compare the predictive value of strategies for collateral blood flow assessment with dynamic computed tomographic angiography (CTA) and conventional single-phase CT angiography. Methods— Patients with a proximal middle cerebral artery occlusion underwent noncontrast CT, single-phase CTA and whole brain CT perfusion/dynamic CTA within 9 hours after stroke onset. We defined poor outcome as a score on the modified Rankin Scale score of ≥3. The association between collateral score and clinical outcome at 3 months was analyzed with Poisson regression. The prognostic value of collateral scoring with dynamic CTA and single-phase CTA in addition to age, stroke severity, and noncontrast CT was assessed with logistic regression and summarized with the area under the curve. Results— Seventy patients were included, with a mean age of 68 years. We observed an increased risk of poor outcome in patients with poor collaterals on single-phase CTA (risk ratio, 1.8; 95% confidence interval, 1.0–3.1) and on dynamic CTA (risk ratio, 2.0; 95% confidence interval, 1.5–2.7). The prediction of poor clinical outcome by means of collateral adjustment was better with dynamic CTA (area under the curve, 0.84; likelihood ratio test P<0.01) than by single-phase CTA (area under the curve, 0.80; likelihood ratio test P=0.33). Conclusions— Collateral assessment with dynamic CTA better predicts clinical outcome at 3 months than single-phase conventional CTA. Clinical Trial Registration— URL: http://www.trialregister.nl/trialreg. Unique identifier: NTR1804. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00880113.

ELAPSS score for prediction of risk of growth of unruptured intracranial aneurysms.

Objective: To develop a risk score that estimates 3-year and 5-year absolute risks for aneurysm growth. Methods: From 10 cohorts of patients with unruptured intracranial aneurysms and follow-up imaging, we pooled individual data on sex, population, age, hypertension, history of subarachnoid hemorrhage, and aneurysm location, size, aspect ratio, and shape but not on smoking during follow-up and family history of intracranial aneurysms in 1,507 patients with 1,909 unruptured intracranial aneurysms and used aneurysm growth as outcome. With aneurysm-based multivariable Cox regression analysis, we determined predictors for aneurysm growth, which were presented as a risk score to calculate 3-year and 5-year risks for aneurysm growth by risk factor status. Results: Aneurysm growth occurred in 257 patients (17%) and 267 aneurysms (14%) during 5,782 patient-years of follow-up. Predictors for aneurysm growth were earlier subarachnoid hemorrhage, location of the aneurysm, age >60 years, population, size of the aneurysm, and shape of the aneurysm (ELAPSS). The 3-year growth risk ranged from <5% to >42% and the 5-year growth risk from <9% to >60%, depending on the risk factor status. Conclusions: The ELAPSS score consists of 6 easily retrievable predictors and can help physicians in decision making on the need for and timing of follow-up imaging in patients with unruptured intracranial aneurysms.

Intra-Arterial Treatment in a Child with Embolic Stroke Due to Atrial Myxoma

Arterial ischaemic stroke is an important cause of morbidity in children. Timely diagnosis is necessary for acute stroke treatment but can be challenging in clinical practice. Due to a paucity of data there are no specific recommendations regarding the use of mechanical thrombectomy devices in current paediatric stroke guidelines. A 14-year-old boy presented with a severe acute left hemisphere stroke due to a proximal middle cerebral artery occlusion caused by emboli from an atrial myxoma. No clinical improvement was seen after administration of intravenous thrombolysis. Subsequent mechanical thrombectomy with a second-generation stent-based thrombectomy device resulted in successful recanalization and clinical improvement. To our knowledge, this is the first report of mechanical thrombectomy in a child with acute embolic stroke caused by atrial myxoma.

Clot Burden Score on Baseline Computerized Tomographic Angiography and Intra-Arterial Treatment Effect in Acute Ischemic Stroke

Background and Purpose— A high clot burden score (CBS) is associated with favorable outcome after intravenous treatment for acute ischemic stroke. The added benefit of intra-arterial treatment might be less in these patients. The aim of this exploratory post hoc analysis was to assess the relation of CBS with neurological improvement and endovascular treatment effect. Methods— For 499 of 500 patients in the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the CBS was determined. Ordinal logistic regression models with and without main baseline prognostic variables were used to assess the association between CBS (continuous or dichotomized at CBS of 6) and a shift toward better outcome on the modified Rankin Scale. The model without main baseline prognostic variables only included treatment allocation and CBS. Models with and without a multiplicative interaction term of CBS and treatment were compared using the &khgr;2 test to assess treatment effect modification by CBS. Results— Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale; adjusted common odds ratio per point CBS was 1.12 (95% confidence interval, 1.04–1.20]. Dichotomized CBS had an adjusted common odds ratio of 1.67 (95% confidence interval, 1.12–2.51). Both effect estimates were slightly attenuated by adding baseline prognostic variables. The addition of the interaction terms did not significantly improve the fit of the models. There was a small and insignificant increase of intra-arterial treatment efficacy in the high CBS group. Conclusions— A higher CBS is associated with improved outcome and may be used as a prognostic marker. We found no evidence that CBS modifies the effect of intra-arterial treatment. Clinical Trial Registration— URL: http://www.trialregister.nl. Unique identifier: NTR1804. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN10888758.