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BACKGROUND: Hypertension alters the structure and function of cerebral blood vessels, and is an important risk factor for stroke and cerebral small vessel disease (cSVD). However, the pathophysiological process is not yet well understood. This study aimed to investigate the relationship between the pulsatility measures in small perforating arteries and hypertension, since hypertension-induced arterial stiffening may lead to a higher blood flow pulsatility and lower damping.METHODS: We examined 28 patients with essential hypertension and 25 age-and sex-matched healthy controls (mean age: 63.4, range: 43-81 years, 26 males). Blood flow velocity waveforms were acquired in the lenticulostriate arteries (LSAs) and the middle cerebral artery using phase-contrast MRI at 7 Tesla. Several cSVD markers were scored. The velocity and pulsatility measures were compared between the hypertensives and controls.RESULTS: A higher pulsatility index (PI) in the LSAs and a lower damping factor (DF) was found in the hypertensive compared to the normotensive group (P=0.015, P=0.015, respectively), but no association was found for the PI in the middle cerebral artery. Higher systolic and mean arterial pressures were associated with higher PI in the LSA and DF. For diastolic blood pressure, only an association with a lower DF was found. Adjusting for cSVD score did not alter these relationships.CONCLUSIONS: This study shows a higher PI in the LSAs and a lower DF in subjects with hypertension, independent of cSVD presence. This supports the hypothesis that hypertension-induced arterial remodeling may alter the intracerebral blood flow velocity profiles, which could eventually contribute to cerebral tissue damage.

Background: Early neurological deterioration (END) after endovascular treatment (EVT) in patients with anterior circulation acute ischemic stroke (AIS) is associated with poor outcome. END may remain unexplained by parenchymal hemorrhage (UnEND). We aim to analyze the risk factors of UnEND in the medical management (MM) and EVT arms of the HERMES study. Methods: We conducted a post-hoc analysis of anterior AIS patients who underwent EVT for proximal anterior occlusions. Risk factors of UnEND, defined as a worsening of ≥4 points between baseline National Institutes of Health Stroke Scale (NIHSS) and NIHSS at 24 hours without hemorrhage, were compared between both arms using mixed logistic regression models adjusted for baseline characteristics. An interaction analysis between the EVT and MM arms for risk factors of UnEND was conducted. Results: Among 1723 patients assessable for UnEND, 160 patients experienced an UnEND (9.3%), including 9.1% (78/854) in the EVT arm and 9.4% (82/869) in the MM arm. There was no significant difference in the incidence of UnEND between the two study arms. In the EVT population, independent risk factors of UnEND were lower baseline NIHSS, higher baseline glucose, and lower collateral grade. In the MM population, the only independent predictor of UnEND was higher baseline glucose. However, we did not demonstrate an interaction between EVT and MM for baseline factors as risk factors of UnEND. UnEND was, similarly in both treatment groups, a significant predictor of unfavorable outcome in both the EVT (p<0.001) and MM (p<0.001) arms. Conclusions: UnEND is not an uncommon event, with a similar rate which ever treatment arm is considered. In the clinical scenario of AIS due to large vessel occlusion, no patient-related factor seems to increase the risk for UnEND when treated by EVT compared with MM.

Aims Cardiovascular disease (CVD) has been suggested to accelerate cognitive decline and to be a risk factor for dementia, but still little is known about the cognitive course after a first cardiovascular event. Therefore, the present study aims to investigate the cognitive trajectories in both prevalent and incident CVD over a 12-year time period in the general population. Methods and results Cognitively healthy participants (age 24-82 years, n = 1823) of a prospective cohort study were serially assessed at baseline, 6 and 12 years. Verbal memory, executive function, and information processing speed were analysed in adults with prevalent, incident, and no CVD. Random effects models were used to test the association between CVD and change in cognitive function over time. At baseline, participants with prevalent CVD showed more decline in memory and information processing speed than healthy controls. Participants with incident CVD also showed more decline in these cognitive domains, but this was only significant in the follow-up period from 6 to 12 years. Associations were more pronounced in participants aged younger than 65 years at baseline, and in sub-analyses with angina pectoris or myocardial infarction as the most prevalent CVD conditions. Conclusion Prevalent and incident CVD predict cognitive decline in middle-aged individuals. Findings for incident CVD suggest that the onset of decline is linked in time with the vascular event itself. Timely CVD management may delay the onset of decline.

Background and Purpose: Acute ischemic stroke due to large vessel occlusion is uncommon in young adults. We assessed stroke cause in young patients and compared their outcomes after endovascular thrombectomy with older patients. Methods: We used data (March 2014 until November 2017) of patients with an anterior circulation large vessel occlusion stroke from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a nationwide, prospective study on endovascular thrombectomy in the Netherlands. We compared young patients (18-49 years) with older patients (>= 50 years). Outcomes included modified Rankin Scale score after 90 days (both shift and dichotomized analyses), expanded Thrombolysis in Cerebral Infarction score, and symptomatic intracranial hemorrhage. Analyses were adjusted for confounding. Results: We included 3256 patients, 310 (10%) were 18 to 49 years old. Young patients had lower median National Institutes of Health Stroke Scale scores (14 versus 16, P<0.001) and less cardiovascular comorbidities than older patients. Stroke etiologies in young patients included carotid dissection (16%), cardio-embolism (15%), large artery atherosclerosis (10%), and embolic stroke of undetermined source (31%). Clinical outcome was better in young than older patients (acOR for modified Rankin Scale shift: 1.8 [95% CI, 1.5-2.2]; functional independence [modified Rankin Scale score 0-2] 61 versus 39% [adjusted odds ratio, 2.1 [95% CI, 1.6-2.8]); mortality 7% versus 32%, adjusted odds ratio, 0.2 [95% CI, 0.1-0.3]). Symptomatic intracranial hemorrhage occurred less frequently in young patients (3% versus 6%, adjusted odds ratio, 0.5 [95% CI, 0.2-1.00]). Successful reperfusion (expanded Thrombolysis in Cerebral Infarction Score 2b-3) did not differ between groups. Onset to reperfusion time was shorter in young patients (253 versus 255 minutes, adjusted B in minutes 12.4 [95% CI, 2.4-22.5]). Concl

Background and Purpose: Computed tomography perfusion imaging allows estimation of tissue status in patients with acute ischemic stroke. We aimed to improve prediction of the final infarct and individual infarct growth rates using a deep learning approach. Methods: We trained a deep neural network to predict the final infarct volume in patients with acute stroke presenting with large vessel occlusions based on the native computed tomography perfusion images, time to reperfusion and reperfusion status in a derivation cohort (MR CLEAN trial [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands]). The model was internally validated in a 5-fold cross-validation and externally in an independent dataset (CRISP study [CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project]). We calculated the mean absolute difference between the predictions of the deep learning model and the final infarct volume versus the mean absolute difference between computed tomography perfusion imaging processing by RAPID software (iSchemaView, Menlo Park, CA) and the final infarct volume. Next, we determined infarct growth rates for every patient. Results: We included 127 patients from the MR CLEAN (derivation) and 101 patients of the CRISP study (validation). The deep learning model improved final infarct volume prediction compared with the RAPID software in both the derivation, mean absolute difference 34.5 versus 52.4 mL, and validation cohort, 41.2 versus 52.4 mL (P<0.01). We obtained individual infarct growth rates enabling the estimation of final infarct volume based on time and grade of reperfusion. Conclusions: We validated a deep learning-based method which improved final infarct volume estimations compared with classic computed tomography perfusion imaging processing. In addition, the deep learning model predicted individual infarct growth rates which could enable the introduction of tissue clocks during the

Background Post-stroke cognitive impairment (PSCI) occurs in approximately half of people in the first year after stroke. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations predictive of PSCI is unavailable. We aimed to identify infarct locations most strongly predictive of PSCI after acute ischaemic stroke and use this information to develop a prediction model. Methods In this large-scale multicohort lesion-symptom mapping study, we pooled and harmonised individual patient data from 12 cohorts through the Meta-analyses on Strategic Lesion Locations for Vascular Cognitive Impairment using Lesion-Symptom Mapping (Meta VCI Map) consortium. The identified cohorts (as of Jan 1, 2019) comprised patients with acute symptomatic infarcts on CT or MRI (with available infarct segmentations) and a cognitive assessment up to 15 months after acute ischaemic stroke onset. PSCI was defined as performance lower than the fifth percentile of local normative data, on at least one cognitive domain on a multidomain neuropsychological assessment or on the Montreal Cognitive Assessment. Voxel-based lesion-symptom mapping (VLSM) was used to calculate voxel-wise odds ratios (ORs) for PSCI that were mapped onto a three-dimensional brain template to visualise PSCI risk per location. For the prediction model of PSCI risk, a location impact score on a 5-point scale was derived from the VLSM results on the basis of the mean voxel-wise coefficient (ln[OR]) within each patient's infarct. We did combined internal-external validation by leave-one-cohort-out cross-validation for all 12 cohorts using logistic regression. Predictive performance of a univariable model with only the location impact score was compared with a multivariable model with addition of other clinical PSCI predictors (age, sex, education, time interval between stroke onset and cognitive assessment, history of stroke, and total infarct volume). Testing of visual ratings was d

Alteplase with EVT versus EVT Alone for Stroke Trials involving Asian patients with acute stroke have suggested that endovascular treatment alone is not inferior to the usual practice of thrombolysis before endovascular treatment. This trial involving European patients did not show noninferiority or superiority of endovascular treatment alone.Background The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. Methods We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. Results The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). Conclusions In

Background and Purpose:Thrombectomy with stent retriever and direct aspiration are equally effective in the endovascular treatment of anterior circulation acute ischemic stroke. We report efficacy and safety of initial treatment technique per occlusion segment.Methods:For this study, we analyzed data from the MR CLEAN Registry, a prospective, observational study in all centers that perform endovascular therapy in the Netherlands. We used ordinal logistic regression analysis to compare clinical and technical results of first line direct aspiration treatment with that of stent retriever thrombectomy stratified for occlusion segment. Primary outcome measure was functional outcome at 3 months. Secondary outcome measures included reperfusion grade expressed as the extended Thrombolysis in Cerebral Infarction score, periprocedural complication risk, time to reperfusion, and mortality.Results:Of the 2282 included patients, 1658 (73%) were initially treated with stent retriever and 624 (27%) with aspiration. Four hundred sixty-two patients had an occlusion of the intracranial part of the carotid artery, 1349 of the proximal middle cerebral artery, and 471 of the distal parts of the middle cerebral artery. There was no difference in functional outcome between aspiration and stent retriever thrombectomy (odds ratio, 1.0 [95% CI, 0.9-1.2]) in any of the occlusion segments (P value for interaction=0.2). Reperfusion rate was higher in the aspiration group (odds ratio, 1.4 [95% CI, 1.1-1.6]) and did not differ between occlusion segments (P value for interaction=0.6). Procedure times were shorter in the aspiration group (minutes 50 versus 65 minutes; P<0.0001). There was no difference in periprocedural complications or mortality.Conclusions:In unselected patients with anterior circulation infarcts, we observed equal functional outcome of aspiration and stent retriever thrombectomy in all occlusion segments. When aspiration was the first line treatment modality, reperfusion rate

Objective: Epileptic seizures are a common complication after stroke. The relation between occurrence of seizures after stroke and long-term mortality remains elusive. We aimed to assess whether seizures in an early or late phase after ischemic stroke are an independent determinant of long-term mortality. Methods: We prospectively included and followed 444 ischemic stroke patients with a first-ever supratentorial brain infarct for at least 2 years after their stroke regarding the occurrence of seizures. The final follow-up for mortality is from April 2015 (follow-up duration 24.5–27.8 years, mean 26.0 years, SD 0.9 years). We compared patients with early-onset seizures with all seizure-free patients, whereas the patients with late-onset seizures were compared with the 1-week survivors without any seizures. We used Cox-regression analyses to correct for possible confounding factors. Results: Kaplan–Meier analysis showed significantly higher mortality for the patients with early-onset seizures (p = 0.002) but after correction for known risk factors for (long term) mortality early-onset seizures had no independent influence on long-term mortality (HR 1.09; 95% CI 0.64–1.85). In patients with late-onset seizures, no significant influence from late-onset seizures on long-term mortality was found (univariate p = 0.717; multivariate HR 0.81; 95% CI 0.54–1.20). Conclusion: Both early-onset and late-onset seizures do not influence long-term mortality after ischemic stroke.

Introduction: Stroke etiology and outcome after ischemic stroke differ between men and women. We examined if sex modifies the effect of intra-arterial treatment (IAT) in a randomized clinical trial of IAT for acute ischemic stroke in the Netherlands (MR CLEAN). Patients and Methods: The primary outcome was the score on the modified Rankin scale at 90 days. We tested for interaction between sex and treatment and estimated the treatment effect by sex with multiple ordinal logistic regression with adjustment for prognostic factors. Results: All 500 patients were included in the analysis; 292 (58.4%) were men. The treatment effect (adjusted common odds ratio) was 2.39 [95% confidence interval (CI) 1.55-3.68] in men and 0.99 (95% CI 0.60-1.66) in women (pinteraction = 0.016). In women, mortality was higher in the intervention group than in the control group (24 vs. 15%, p = 0.07). Serious adverse events occurred more often in women than in men undergoing intervention. There were no differences in neuro-imaging outcomes. Discussion and Conclusion: Contrary to other studies, we found a significant interaction between sex and treatment effect in the MR CLEAN trial. Pooled analyses of all published thrombectomy trials did not confirm this finding. In MR CLEAN, women seem to have a slightly more unfavorable profile, causing higher mortality and more serious adverse events, but insufficient to explain the absence of an overall effect. This suggests a play of chance and makes it clear that IAT should not be withheld in women.

Purpose: Although cytologic examination of CSF is the primary method for the evaluation of response to therapy for leptomeningeal metastases (LMMs), the procedure's sensitivity decreases throughout the course of protracted therapy. We studied whether this response could be monitored more accurately through the detection of numerical chromosomal aberrations by interphase cytogenetics, using fluorescence in situ hybridization (FISH), Patients and Methods: Seven patients treated for LMMs and with a known numerical aberration for chromosome; 1 in their pretreatment CSF were included in this study, Up to 16 consecutive CSF samples were analyzed by means of the fluorescence in situ hybridization (FISH) technique for cells with aberrant chromosome 1 content, The results of routine cytology and FISH analyses were compared and were correlated with each patient's neurologic status. Results: Routine cytology detected malignancies in only 24 of the 76 samples, all of which were classified as chromosomally abnormal by FISH (except for two samples that could not be evaluated). Moreover, FISH demonstrated aneusomic cells in 32 additional samples, which could therefore be classified as malignant, The FISH results correlated better with patient neurologic status in that more malignant cells were detected in the CSF of neurologically deteriorating patients. Conclusion: Using FISH in addition to performing routine cytologic examination of CSF leer to a more accurate evaluation of response to treatment in patients treated for LMMs. J Clin Oncol 18:2053-2058.