Ewoud J. van Dijk

Background: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. Methods: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). Results: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P P P <0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07–1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98–1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99–1.30]). Outcomes were consistent in the analysis per chronological quartile. Conclusions: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.

Background and Purpose: Blinded outcome assessment in trials with prospective randomized open blinded end point design is challenging. Unblinding can result in misclassified outcomes and biased treatment effect estimates. An outcome adjudication committee assures blinded outcome assessment, but the added value for trials with prospective randomized open blinded end point design and subjective outcomes is unknown. We aimed to assess the degree of misclassification of modified Rankin Scale (mRS) scores by a central assessor and its impact on treatment effect estimates in a stroke trial with prospective randomized open blinded end point design. Methods: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was the mRS at 90 days. Standardized, algorithm-based telephone interviews to assess the mRS were conducted from a central location by an experienced research nurse, unaware but not formally blinded to treatment allocation (central assessor). Masked reports of these interviews were adjudicated by a blinded outcome committee. Misclassification was defined as an incorrect classification of the mRS by the central assessor. The effect of endovascular treatment on the mRS was assessed with multivariable ordinal logistic regression. Results: In MR CLEAN, 53/500 (10.6%) of the mRS scores were misclassified. The degree and direction of misclassification did not differ between treatment arms ( P =0.59). Benefit of endovascular treatment was shown on the mRS when scored by the central assessor (adjusted common odds ratio, 1.60 [95% CI, 1.16–2.21]) and the outcome adjudication committee (adjusted common odds ratio, 1.67 [95% CI, 1.21–2.20]). Conclusions: Misclassification by the central assessor was small, randomly distributed over treatment arms, and did not affect treatment effect estimates. This study suggests that the added value of a blinded outcome adjudication committee is limited in a stroke trial with prospective randomized open blinded end point design applying standardized, algorithm-based outcome assessment by a central assessor, who is unaware but not formally blinded to treatment allocation. Registration: URL: https://www.isrctn.com ; Unique identifier: ISRCTN10888758.

Background and Purpose—: The clinical diagnosis of a transient ischemic attack (TIA) can be difficult. Evidence-based criteria hardly exist. We evaluated if the recently proposed Explicit Diagnostic Criteria for TIA (EDCT), an easy to perform clinical tool focusing on type, duration, and mode of onset of clinical features, would facilitate the clinical diagnosis of TIA. Methods—: We used data from patients suspected of a TIA by a general practitioner and referred to a TIA service in the region of Utrecht, the Netherlands, who participated in the MIND-TIA (Markers in the Diagnosis of TIA) study. Information about the clinical features was collected with a standardized questionnaire within 72 hours after onset. A panel of 3 experienced neurologists ultimately determined the definite diagnosis based on all available diagnostic information including a 6-month follow-up period. Two researchers scored the EDCT. Sensitivity, specificity, and predictive values of the EDCT were assessed using the panel diagnosis as reference. A secondary analysis was performed with modified subcriteria of the EDCT. Results—: Of the 206 patients, 126 (61%) had a TIA (n=104) or minor stroke (n=22), and 80 (39%) an alternative diagnosis. Most common alternative diagnoses were migraine with aura (n=24; 30.0%), stress related or somatoform symptoms (n=16; 20.0%), and syncope (n=9; 11.3%). The original EDCT had a sensitivity of 98.4% (95% CI, 94.4–99.8) and a specificity of 61.3% (49.7–71.9). Negative and positive predictive values were 96.1% (86.0–99.0) and 80.0% (75.2–84.1), respectively. The modified EDCT showed a higher specificity of 73.8% (62.7–83.0) with the same sensitivity and a similar negative predictive value of 96.7%, but a higher positive predictive value of 85.5% (80.3–89.5). Conclusions—: The EDCT has excellent sensitivity and negative predictive value and could be a valuable diagnostic tool for the diagnosis of TIA.

The Dutch Parelsnoer Institute-Cerebrovascular accident (CVA) Study is part of the Parelsnoer Institute (PSI), initiated in 2007 by the Netherlands Federation of University Medical Centers (NFU). PSI is a cooperation of all eight Dutch University Medical Centers (UMCs) and aims at building large prospectively collected datasets with uniformly and standardized storage of biomaterials for complex diseases. Currently, PSI covers 18 disease-specific cohorts called ‘Pearls’, and this number is still growing. One of these cohorts is the Stroke or CVA Pearl. For each of the cohorts, PSI offers the UMCs an infrastructure and standard procedures for storing the specific biomaterials in their certified biobanks. Clinical data are stored in a central database after being pseudonymized to ensure patient privacy. For the Parelsnoer Institute-CVA Study, blood for genetic analysis, serum and plasma are collected according to nationally agreed standards. Currently (November 2017) the Stroke Pearl has stored blood samples with prospectively obtained clinical data of around 6000 patients in all UMCs combined. Blood samples and data are available for all researchers with a methodologically valid research proposal. Funding statement: PSI was founded in 2007 with a five year grant from the Dutch Government. From 2011 until now PSI is funded and facilitated by the Netherlands Federation of University Medical Centers (NFU) and its member institutions, independent of external funds. Additional funds from governmental sources, industry sponsors and charity are used for the analysis on the existing data and the expansion of PSI with new diseases.

Background and Purpose—: Although by definition transient, both transient ischemic attack (TIA) and transient neurological attack (TNA) are associated with cognitive impairment. Determinants and course of cognitive function afterward are, however, unclear. We prospectively determined cognitive performance after TIA and TNA in relation to clinical diagnosis and diffusion-weighted imaging (DWI) results. Methods—: TIA and TNA patients aged ≥45 years without prior stroke or dementia underwent comprehensive cognitive assessment and magnetic resonance imaging within 7 days after the qualifying event. Cognitive tests were repeated after 6 months. Domain-specific compound z scores based on the baseline mean and SD were calculated. Repeated-measures analysis was used to test for differences in domain-specific cognitive performance over time between DWI-positive and DWI-negative patients, as well as between TIA and TNA patients. Results—: One hundred twenty-one patients were included (mean age (SD), 64.6 years (9.2 years), 60% TIA and 40% TNA) of whom 32 (26%) had a DWI lesion. Executive function performance decreased over time (mean change in compound score −0.23; P =0.01 adjusted for age, sex, education), whereas attention improved (0.11; P =0.02), and information processing speed and episodic memory remained unchanged. Patients with a DWI lesion had worse executive function at baseline than those without a DWI lesion (compound scores −0.26 versus 0.08; P =0.048), which persisted throughout the study period ( P =0.04). Clinical diagnosis (TIA or TNA) was not related to cognitive function over time. Conclusions—: Executive function declines during the first 6 months after TIA or TNA. Patients with an initial DWI lesion have persisting worse executive function than those without.

Due to their young age young stroke survivors have to cope with a dramatic impact on their life for the decades to come. We investigated the sex-specific very long-term functional outcome after transient ischemic attack (TIA) and ischemic stroke (IS) in adults aged 18–50 years. This study is part of a cohort study among 619 first-ever young ischemic stroke patients, admitted to our department between January 1, 1980 and November 1, 2010. Functional outcome was assessed during follow-up in 2009–2011 and in 2014–2015 with the modified Rankin Scale (mRS) and instrumental Activities of Daily Living scale (iADL). Risk factors for a poor functional outcome (mRS > 2 and iADL < 8) were calculated by logistic regression analysis. After a mean follow-up of 13.9 (SD 8.2) years, 24.5 % of TIA patients and 44.7 % of IS patients had a poor functional outcome (mRS > 2). When assessing the survivors, 15.2 % of TIA patients and 22.9 % of IS patients had a poor outcome as assessed by iADL. The strongest baseline predictors of poor outcome were female sex (OR 2.7, 95 % CI 1.5–5.0) and baseline NIHSS (OR 1.1, 95 % CI 1.1–1.2 per point increase). In conclusion, 14 years after an ischemic cerebrovascular event in young adults, one out of five IS survivors and one out of ten TIA survivors is still dependent in daily life, with a two to threefold higher risk of a poor outcome in women. This includes a period of life, during which important decisions regarding work and family life have to be made.

Transient ischemic attack (TIA) can be difficult to diagnose. Episodes of acute atypical or nonfocal neurological symptoms, referred to as transient neurological attack (TNA), are as prevalent as TIAs. Diffusion‐weighted imaging (DWI) provides evidence of acute cerebral ischemia in a third of TIA patients. We now report that DWI shows acute ischemia in 23% of patients clinically diagnosed as TNA by experienced stroke neurologists. This questions the accuracy of clinically diagnosing TIA and suggests added value for early magnetic resonance imaging after an episode of acute onset atypical or nonfocal neurological symptoms. Ann Neurol 2015;78:1005–1010