Marieke C. Visser

Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study.

Background and Purpose— Vascular dementia (VaD) is thought to be the most common cause of dementia after Alzheimer’s disease. The commonly used International Workshop of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (AIREN) criteria for VaD necessitate evidence of vascular disease on CT or MRI of the brain. The purposes of our study were to operationalize the radiological part of the NINDS-AIREN criteria and to assess the effect of this operationalization on interobserver agreement. Methods— Six experienced and 4 inexperienced observers rated a set of 40 MRI studies of patients with clinically suspected VaD twice using the NINDS-AIREN set of radiological criteria. After the first reading session, operational definitions were conceived, which were subsequently used in the second reading session. Interobserver reproducibility was measured by Cohen’s &kgr;. Results— Overall agreement at the first reading session was poor (&kgr;=0.29) and improved slightly after application of the additional definitions (&kgr;=0.38). Raters in the experienced group improved their agreement from almost moderate (&kgr;=0.39) to good (0.62). The inexperienced group started out with poor agreement (&kgr;=0.17) and did not improve (&kgr;=0.18). The experienced group improved in both the large- and small-vessel categories, whereas the inexperienced group improved generally in the extensive white matter hyperintensities categories. Conclusions— Considerable interobserver variability exists for the assessment of the radiological part of the NINDS-AIREN criteria. Use of operational definitions improves agreement but only for already experienced observers.

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.

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.

What Makes Children Behave Aggressively? : The Inner Logic of Dutch Children in Special Education

The ambiguous results of existing intervention programmes show the need for new ways in research on aggression among children. The present study focuses on the children’s own perspective on their aggressive behaviour. Based on a constructivist approach, the inner logic of narratives about peer conflicts of 64 children in Dutch special education was analysed. Contrary to the much used dichotomy of reactive and proactive aggression, we found a more differentiated picture. Children use aggression: to get understanding for their situation; to escape from the conflict situation; because of inner conflicts; to get revenge; and for the fun of bullying. The study makes clear that, from the perspective of the children, aggressive behaviour is closely related to the peer culture at school. Moreover, some children need individual treatment and support, because of specific concerns related to self‐regulation that make them behave aggressively.

Migraine and Cerebrovascular Atherosclerosis in Patients With Ischemic Stroke

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

The Dutch String-of-Pearls Stroke Study: Protocol of a large prospective multicenter genetic cohort study

Background In the last couple of years, genome-wide association studies have largely altered the scope in genetic research in diseases in which both environmental and genetic risk factors contribute to the disease. To date, the genetic risk loci identified in stroke have lagged behind those in other complex diseases, possibly because of the heterogeneity of stroke phenotypes. Sufficiently large cohorts with well-defined and detailed phenotyping of stroke patients are needed to identify additional genetic risk loci. Design The String-of-Pearls Institute is a unique partnership between all eight University Medical Centers in the Netherlands. It was established in 2007 by the Netherlands Federation of University Medical Centers, and it conducts a large prospective cohort study in which comprehensive clinical data, detailed phenotyping of stroke, imaging data, and biomaterials are collected in a large cohort of stroke patients. Aims The study aims (1) to collect a sufficiently large prospective cohort of stroke patients, with well-defined phenotypes; (2) to collect blood samples and DNA in a standardized infrastructure, allowing for storing and analyzing the samples in a uniform way; (3) to investigate associations between genetic risk loci and stroke; (4) to create possibilities to perform epidemiological studies in a well-defined hospital-based cohort of stroke patients; and (5) to allow for pooling data with other large ongoing genetic stroke studies.

Practice Variation in Long-term Secondary Stroke Prevention in The Netherlands

BACKGROUND Stroke guidelines emphasize the importance of adequate vascular risk factor assessment and management in transient ischemic attack (TIA) and ischemic stroke patients, but it is not clear how these guidelines are applied in routine clinical practice. The limited data that are available indicate that TIA and ischemic stroke patients often do not receive the recommended interventions. The aim of this study was to investigate practice variations in long-term secondary stroke prevention in The Netherlands. METHODS Between June and December 2013, an invitation for a web-based survey was sent to 90 Dutch neurologists with a special interest in stroke neurology. This web-based survey contained questions regarding the organization of outpatient care for TIA and ischemic stroke patients after initial hospital assessment, pharmacologic treatment, and nonpharmacologic strategies for long-term secondary prevention. RESULTS In total, 84 (93%) neurologists completed the survey. Although nearly all respondents reported that they follow-up TIA and ischemic stroke patients after initial hospital assessment, the number of follow-up visits and the follow-up duration were variable. A similar variation was found in treatment targets levels for both blood pressure and low-density lipoprotein cholesterol. Regarding nonpharmacologic strategies for long-term secondary stroke prevention, most respondents inform their TIA and ischemic stroke patients about the importance of smoking cessation. There is considerably less attention for the other lifestyle risk factors. CONCLUSIONS We found considerable practice variation in long-term secondary stroke prevention. These variations may have an impact on the risk for stroke recurrence and cardiovascular disease in general.

Variation in Organization of Transient Ischemic Attack Care in The Netherlands. A Nationwide Survey Study

BACKGROUND Previous research has shown the importance of urgent initiation of antiplatelet therapy after transient ischemic attack (TIA) to reduce the risk of stroke. Many hospitals in the Netherlands have therefore implemented rapid pathways for assessment of patients with TIA. Dutch stroke guidelines lack clear directives for organization of TIA assessment and thus allow for variation. The aim of this study was to investigate variation in organization of TIA assessment in Dutch hospitals. METHODS One neurologist per hospital (of 88 Dutch hospitals) with special interest in stroke was invited to participate in a web-based survey addressing the organization, content, and timing of TIA assessment. RESULTS Seventy (80%) neurologists completed the survey, all of whom reported performing TIA assessment in their hospital. There was considerable variation in the method of application and the location of assessment. In 10% of the hospitals, patients with TIA are always admitted to the ward. The content of diagnostics is fairly similar, but hospitals vary in the extent of cardiological workup. Almost all hospitals aim for a swift start of assessment as directed by guidelines, but access time differs. Eighty-six percent of respondents reported that antiplatelet therapy is usually initiated before assessment, based on history. CONCLUSIONS This study showed variation in organization of TIA assessment in Dutch hospitals, especially regarding location within the hospital, time to assessment after announcement, and cardiological workup. Further research is needed to investigate implications of this variation for quality of care.