Introduction: Carotid atherosclerotic intraplaque hemorrhage (IPH) predicts stroke. Patients with a history of stroke are treated with antiplatelet agents to prevent secondary cardiovascular... Show moreIntroduction: Carotid atherosclerotic intraplaque hemorrhage (IPH) predicts stroke. Patients with a history of stroke are treated with antiplatelet agents to prevent secondary cardiovascular events. A positive association between previous antiplatelet use and IPH was reported in a cross-sectional analysis. We investigated the changes in IPH over 2 years in patients who recently started versus those with continued antiplatelet use. Methods: In the Plaque at Risk (PARISK) study, symptomatic patients with <70% ipsilateral carotid stenosis underwent carotid plaque magnetic resonance imaging (MRI) at the baseline and after 2 years to determine IPH presence and volume. Participants were categorized into new users (starting antiplatelet therapy following the index event) and continued users (previous use of antiplatelet therapy before the index event). The association between previous antiplatelet therapy and the presence of IPH at baseline MRI was investigated using multivariable logistic regression analysis. The IPH volume change over a period of 2 years, defined as the difference in volume between follow-up and baseline, was investigated in each group with a Wilcoxon signed-rank test. The IPH volume change was categorized as progression, regression, or no change. Using multivariable logistic regression, we investigated the association between new antiplatelet use and (1) newly developed ipsilateral or contralateral IPH and (2) IPH volume progression. Results: A total of 108 patients underwent carotid MRI at the baseline and follow-up. At the baseline, previous antiplatelet therapy was associated with any IPH (OR = 5.6, 95% CI: 1.3–23.1; p = 0.02). Ipsilateral IPH volume did not change significantly during the 2 years in patients who continued receiving antiplatelet agents (86.4 mm3 [18.2–235.9] vs. 59.3 mm3 [11.4–260.3]; p = 0.6) nor in the new antiplatelet users (n = 31) (61.5 mm3 [0.0–166.9] vs. 27.7 mm3 [9.5–106.4]; p = 0.4). Similar results of a nonsignificant change in contralateral IPH volume during those 2 years were observed in both groups (p > 0.05). No significant associations were found between new antiplatelet use and newly developed IPH at 2 years (odds ratio [OR] = 1.0, 95% CI: 0.1–7.4) or the progression of IPH (ipsilateral: OR = 2.4, 95% CI: 0.3–19.1; contralateral: OR = 0.3, 95% CI: 0.01–8.5). Conclusion: Although the baseline association between IPH and previous antiplatelet therapy was confirmed in this larger cohort, the new onset of antiplatelet therapy after transient ischemic attack/stroke was not associated with the newly developed IPH or progression of IPH volume over the subsequent 2 years. Show less
Kassem, M.; Kam, S.S. de; Velzen, T.J. van; Geest, R. van der; Wagner, B.; Sokolska, M.; ... ; Kooi, M.E. 2023
Purpose: Carotid intraplaque hemorrhage (IPH) on MRI predicts stroke. Magnetization-prepared rapid acquisition gradient (MP-RAGE) is widely used to detect IPH. CE-MRA is used routinely to assess... Show morePurpose: Carotid intraplaque hemorrhage (IPH) on MRI predicts stroke. Magnetization-prepared rapid acquisition gradient (MP-RAGE) is widely used to detect IPH. CE-MRA is used routinely to assess stenosis. Initial studies indicated that IPH can be identified on mask images of CE-MRA, while Time-of-Flight (TOF) images were reported to have high specificity but lower sensitivity. We investigated the diagnostic accuracy of detecting IPH on mask images of CE-MRA and TOF. Methods: Thirty-six patients with >= 50% stenosis enrolled in the ongoing 2nd European Carotid Surgery Trial underwent carotid MRI. A 5-point quality score was used. Inter-observer agreement between two independent readers was determined. The sensitivity and specificity of IPH detection on mask MRA and TOF were calculated with MP-RAGE as a reference standard. Results: Of the 36 patients included in the current analysis, 66/72 carotid arteries could be scored. The interobserver agreements for identifying IPH on MP-RAGE, mask, and TOF were outstanding (K: 0.93, 0.96, and 0.85). The image quality of mask (1.42 +/- 0.66) and TOF (2.42 +/- 0.66) was significantly lower than MP-RAGE (3.47 +/- 0.61). When T1w images were used to delineate the outer carotid wall, very high specificities (>95%) of IPH detection on mask and TOF images were found, while the sensitivity was high for mask images (>81%) and poor for TOF (50–60%). Without these images, the specificity was still high (>97%), while the sensitivity reduced to 62–71%. Conclusion: Despite the lower image quality, routinely acquired mask images from CE-MRA, but not TOF, can be used as an alternative to MP-RAGE images to visualize IPH. Show less
Background:Identification of risk factors and causes of stroke is key to optimize treatment and prevent recurrence. Up to one-third of young patients with stroke have a cryptogenic stroke according... Show moreBackground:Identification of risk factors and causes of stroke is key to optimize treatment and prevent recurrence. Up to one-third of young patients with stroke have a cryptogenic stroke according to current classification systems (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] and atherosclerosis, small vessel disease, cardiac pathology, other causes, dissection [ASCOD]). The aim was to identify risk factors and leads for (new) causes of cryptogenic ischemic stroke in young adults, using the pediatric classification system from the IPSS study (International Pediatric Stroke Study).Methods:This is a multicenter prospective cohort study conducted in 17 hospitals in the Netherlands, consisting of 1322 patients aged 18 to 49 years with first-ever, imaging confirmed, ischemic stroke between 2013 and 2021. The main outcome was distribution of risk factors according to IPSS classification in patients with cryptogenic and noncryptogenic stroke according to the TOAST and ASCOD classification.Results:The median age was 44.2 years, and 697 (52.7%) were men. Of these 1322 patients, 333 (25.2%) had a cryptogenic stroke according to the TOAST classification. Additional classification using the ASCOD criteria reduced the number patients with cryptogenic stroke from 333 to 260 (19.7%). When risk factors according to the IPSS were taken into account, the number of patients with no potential cause or risk factor for stroke reduced to 10 (0.8%).Conclusions:Among young adults aged 18 to 49 years with a cryptogenic ischemic stroke according to the TOAST classification, risk factors for stroke are highly prevalent. Using a pediatric classification system provides new leads for the possible causes in cryptogenic stroke, and could potentially lead to more tailored treatment for young individuals with stroke. Show less
Background and ObjectivesCauses of stroke in young adults differ from those in the elderly individuals, and in a larger percentage,no cause can be determined. To gain more insight into the etiology... Show moreBackground and ObjectivesCauses of stroke in young adults differ from those in the elderly individuals, and in a larger percentage,no cause can be determined. To gain more insight into the etiology of (cryptogenic) stroke in theyoung population, we investigated whether trigger factors, such as short-lasting exposure to toxins orinfection, may play a role.MethodsPatients aged 18–49 years with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) in 17participating centers in the Netherlands completed a questionnaire about exposure to 9 potentialtrigger factors in hazard periods and on a regular yearly basis. A case-crossover design was used toassess relative risks (RRs) with 95% confidence intervals (95% CIs) by the Mantel-Haenszel case-crossover method, for any stroke (ischemic stroke and ICH combined) and for different etiologicsubgroups of ischemic stroke.ResultsOne thousand one hundred forty-six patients completed the questionnaire (1,043 patients withan ischemic stroke and 103 with an ICH, median age 44.0 years, 52.6% men). For any stroke, anincreased risk emerged within 1 hour of cola consumption (RR 2.0, 95% CI 1.5–2.8) and vigorousphysical exercise (RR 2.6, 95% CI 2.2–3.0), within 2 hours after sexual activity (RR 2.4, 95% CI1.6–3.5), within 4 hours after illicit drug use (RR 2.8, 95% CI 1.7–4.9), and within 24 hours afterfever or flu-like disease (RR 14.1, 95% CI 10.5–31.2; RR 13.9, 95% CI 8.9–21.9). Four triggerfactors increased the risk of other determined and cryptogenic ischemic stroke, 3 that of car-dioembolic stroke, 2 that of large vessel atherosclerosis and likely atherothrombotic strokecombined and stroke with multiple causes, and none that of stroke due to small vessel disease.DiscussionWe identified cola consumption, vigorous physical exercise, sexual activity, illicit drug use, fever, andflu-like disease as potential trigger factors for stroke in the young population and found differencesin the type and number of trigger factors associated with different etiologic subgroups of ischemicstroke. These findings might help in better understanding the pathophysiologic mechanisms of(cryptogenic) stroke in the young population. Show less
Background: The optimal management of ipsilateral extracranial internal carotid artery (ICA) stenosis during endovascular treatment (EVT) is unclear. We compared the outcomes of two different... Show moreBackground: The optimal management of ipsilateral extracranial internal carotid artery (ICA) stenosis during endovascular treatment (EVT) is unclear. We compared the outcomes of two different strategies: EVT with vs without carotid artery stenting (CAS). Methods: In this observational study, we included patients who had an acute ischaemic stroke undergoing EVT and a concomitant ipsilateral extracranial ICA stenosis of >= 50% or occlusion of presumed atherosclerotic origin, from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014-2017). The primary endpoint was a good functional outcome at 90 days, defined as a modified Rankin Scale score <= 2. Secondary endpoints were successful intracranial reperfusion, new clot in a different vascular territory, symptomatic intracranial haemorrhage, recurrent ischaemic stroke and any serious adverse event. Results: Of the 433 included patients, 169 (39%) underwent EVT with CAS. In 123/168 (73%) patients, CAS was performed before intracranial thrombectomy. In 42/224 (19%) patients who underwent EVT without CAS, a deferred carotid endarterectomy or CAS was performed. EVT with and without CAS were associated with similar proportions of good functional outcome (47% vs 42%, respectively; adjusted OR (aOR), 0.90; 95% CI, 0.50 to 1.62). There were no major differences between the groups in any of the secondary endpoints, except for the increased odds of a new clot in a different vascular territory in the EVT with CAS group (aOR, 2.96; 95% CI, 1.07 to 8.21). Conclusions: Functional outcomes were comparable after EVT with and without CAS. CAS during EVT might be a feasible option to treat the extracranial ICA stenosis but randomised studies are warranted to prove non-inferiority or superiority. Show less
Background The optimal management of ipsilateral extracranial internal carotid artery (ICA) stenosis during endovascular treatment (EVT) is unclear. We compared the outcomes of two different... Show moreBackground The optimal management of ipsilateral extracranial internal carotid artery (ICA) stenosis during endovascular treatment (EVT) is unclear. We compared the outcomes of two different strategies: EVT with vs without carotid artery stenting (CAS).Methods In this observational study, we included patients who had an acute ischaemic stroke undergoing EVT and a concomitant ipsilateral extracranial ICA stenosis of ≥50% or occlusion of presumed atherosclerotic origin, from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014–2017). The primary endpoint was a good functional outcome at 90 days, defined as a modified Rankin Scale score ≤2. Secondary endpoints were successful intracranial reperfusion, new clot in a different vascular territory, symptomatic intracranial haemorrhage, recurrent ischaemic stroke and any serious adverse event.Results Of the 433 included patients, 169 (39%) underwent EVT with CAS. In 123/168 (73%) patients, CAS was performed before intracranial thrombectomy. In 42/224 (19%) patients who underwent EVT without CAS, a deferred carotid endarterectomy or CAS was performed. EVT with and without CAS were associated with similar proportions of good functional outcome (47% vs 42%, respectively; adjusted OR (aOR), 0.90; 95% CI, 0.50 to 1.62). There were no major differences between the groups in any of the secondary endpoints, except for the increased odds of a new clot in a different vascular territory in the EVT with CAS group (aOR, 2.96; 95% CI, 1.07 to 8.21).Conclusions Functional outcomes were comparable after EVT with and without CAS. CAS during EVT might be a feasible option to treat the extracranial ICA stenosis but randomised studies are warranted to prove non-inferiority or superiority. Show less
Ali, M.; Meij, A. van der; Os, H.J.A. van; Zwet, E.W. van; Spaander, F.H.M.; Hofmeijer, J.; ... ; MR CLEAN Registry Investigators 2022
BackgroundWomen have been reported to have worse outcomes after endovascular treatment (EVT), despite a similar treatment effect in non-clinical trial populations. We aimed to assess sex... Show moreBackgroundWomen have been reported to have worse outcomes after endovascular treatment (EVT), despite a similar treatment effect in non-clinical trial populations. We aimed to assess sex differences at hospital presentation with respect to workflow metrics, prestroke disability, and presenting clinical symptoms. MethodsWe included consecutive patients from the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in The Netherlands (MR CLEAN) Registry (2014-2018) who received EVT for anterior circulation large vessel occlusion (LVO). We assessed sex differences in workflow metrics, prestroke disability (modified Rankin Scale (mRS) score >= 1), and stroke severity and symptoms according to the National Institutes of Health Stroke Scale (NIHSS) score on hospital admission with logistic and linear regression analyses and calculated the adjusted OR (aOR). ResultsWe included 4872 patients (47.6% women). Compared with men, women were older (median age 76 vs 70 years) and less often achieved good functional outcome at 90 days (mRS <= 2: 35.2% vs 46.4%, aOR 0.70, 95% CI 0.60 to 0.82). Mean onset-to-door time was longer in women (2 hours 16 min vs 2 hours 7 min, adjusted delay 9 min, 95% CI 4 to 13). This delay contributed to longer onset-to-groin times (3 hours 26 min in women vs 3 hours 13 min in men, adjusted delay 13 min, 95% CI 9 to 17). Women more often had prestroke disability (mRS >= 1: 41.1% vs 29.1%, aOR 1.57, 95% CI 1.36 to 1.82). NIHSS on admission was essentially similar in men and women (mean 15 +/- 6 vs 15 +/- 6, NIHSS <10 vs >= 10, aOR 0.91, 95% CI 0.78 to 1.06). There were no clear sex differences in the occurrence of specific stroke symptoms. ConclusionWomen with LVO had longer onset-to-door times and more often prestroke disability than men. Raising awareness of these differences at hospital presentation and investigating underlying causes may help to improve outcome after EVT in women. Show less
Introduction: We aimed to investigate the prevalence of cognitive impairment in the subacute phase after transient ischemic attack (TIA) and ischemic stroke (IS), factors associated with a vascular... Show moreIntroduction: We aimed to investigate the prevalence of cognitive impairment in the subacute phase after transient ischemic attack (TIA) and ischemic stroke (IS), factors associated with a vascular cognitive disorder, and the prevalence of subjective cognitive complaints and their relation with objective cognitive performance. Patients and methods: In this multicenter prospective cohort study, we recruited patients with first-ever TIA and IS, aged 18-49 years, between 2013 and 2021 for cognitive assessment up to 6 months after index event. We calculated composite Z-scores for seven cognitive domains. We defined cognitive impairment as a composite Z-score < -1.5. We defined major vascular cognitive disorder as a Z-score < -2.0 in one or more cognitive domains. Results: Fifty three TIA and 545 IS patients completed cognitive assessment with mean time to assessment of 89.7 (SD 40.7) days. The median NIHSS at admission was 3 (interquartile range, 1-5). Cognitive impairment was common in five domains (up to 37%), with similar proportion in TIA and IS patients. Patients with major vascular cognitive disorder had a lower education level, higher NIHSS scores and more frequent lesions in the left frontotemporal lobe than without vascular cognitive disorder (p < 0.05 FDR-corrected). Subjective memory and executive cognitive complaints were present in about two-thirds of the patients, but were weakly associated with objective cognitive performance (beta: -0.32 and -0.21, respectively). Discussion and conclusion: In the subacute phase after TIA or stroke in young adults, cognitive impairment and subjective cognitive complaints are prevalent, but they are weakly associated with each other. Show less
Introduction:We aimed to investigate the prevalence of cognitive impairment in the subacute phase after transient ischemic attack (TIA) and ischemic stroke (IS), factors associated with a vascular... Show moreIntroduction:We aimed to investigate the prevalence of cognitive impairment in the subacute phase after transient ischemic attack (TIA) and ischemic stroke (IS), factors associated with a vascular cognitive disorder, and the prevalence of subjective cognitive complaints and their relation with objective cognitive performance.Patients and methods:In this multicenter prospective cohort study, we recruited patients with first-ever TIA and IS, aged 18–49 years, between 2013 and 2021 for cognitive assessment up to 6 months after index event. We calculated composite Z-scores for seven cognitive domains. We defined cognitive impairment as a composite Z-score < −1.5. We defined major vascular cognitive disorder as a Z-score < −2.0 in one or more cognitive domains.Results:Fifty three TIA and 545 IS patients completed cognitive assessment with mean time to assessment of 89.7 (SD 40.7) days. The median NIHSS at admission was 3 (interquartile range, 1–5). Cognitive impairment was common in five domains (up to 37%), with similar proportion in TIA and IS patients. Patients with major vascular cognitive disorder had a lower education level, higher NIHSS scores and more frequent lesions in the left frontotemporal lobe than without vascular cognitive disorder (p < 0.05 FDR-corrected). Subjective memory and executive cognitive complaints were present in about two-thirds of the patients, but were weakly associated with objective cognitive performance (β: −0.32 and −0.21, respectively).Discussion and conclusion:In the subacute phase after TIA or stroke in young adults, cognitive impairment and subjective cognitive complaints are prevalent, but they are weakly associated with each other. Show less
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross... Show morePrevious genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries. Show less
Introduction We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge... Show moreIntroduction We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge in Dutch comprehensive stroke centers. Furthermore, we studied the association between COVID-19-status and treatment times. Methods We included all patients receiving reperfusion treatment in 17 Dutch stroke centers from May 11th, 2017, until May 11th, 2020. We collected baseline characteristics, National Institutes of Health Stroke Scale (NIHSS) at admission, onset-to-door time (ODT), door-to-needle time (DNT), door-to-groin time (DGT) and COVID-19-status at admission. Parameters during the lockdown (March 15th, 2020 until May 11th, 2020) were compared with those in the same period in 2019, and between groups stratified by COVID-19-status. We used nationwide data and extrapolated our findings to the increasing trend of EVT numbers since May 2017. Results A decline of 14% was seen in reperfusion treatments during lockdown, with a decline in both IVT and EVT delivery. DGT increased by 12 min (50 to 62 min, p-value of < 0.001). Furthermore, median NIHSS-scores were higher in COVID-19 - suspected or positive patients (7 to 11, p-value of 0.004), door-to-treatment times did not differ significantly when stratified for COVID-19-status. Conclusions During the first surge of the COVID-19 pandemic, a decline in acute reperfusion treatments and a delay in DGT was seen, which indicates a target for attention. It also appeared that COVID-19-positive or -suspected patients had more severe neurologic symptoms, whereas their EVT-workflow was not affected. Show less
Amini, M.; Hartog, S.J. den; Leeuwen, N. van; Eijkenaar, F.; Kuhrij, L.S.; Stolze, L.J.; ... ; PERFEQTOS Investigators 2021
Background: Although the provision of performance feedback to healthcare professionals based on data from quality registries is common practice in many fields of medicine, observational studies of... Show moreBackground: Although the provision of performance feedback to healthcare professionals based on data from quality registries is common practice in many fields of medicine, observational studies of its effect on the quality of care have shown mixed results. The objective of this study is to evaluate the effect of performance feedback on the quality of care for acute ischemic stroke.Methods: PERFEQTOS is a stepped wedge cluster randomized trial in 13 hospitals in the Netherlands providing endovascular thrombectomy for ischemic stroke. The primary outcome is the hospital's door-to-groin time. The study starts with a 6-month period in which none of the hospitals receives the performance feedback intervention. Subsequently, every 6 months, three or four hospitals are randomized to cross over from the control to the intervention conditions, until all hospitals receive the feedback intervention. The feedback intervention consists of a dashboard with quarterly reports on patient characteristics, structure, process, and outcome indicators related to patients with ischemic stroke treated with endovascular thrombectomy. Hospitals can compare their present performance with their own performance in the past and with other hospitals. The performance feedback is provided to local quality improvement teams in each hospital, who define their own targets on specific indicators and develop performance improvement plans. The impact of the performance feedback and improvement plans will be evaluated by comparing the primary outcome before and after the intervention.Discussion: This study will provide evidence on the effectiveness of performance feedback to healthcare providers. The results will be actively disseminated through peer-reviewed journals, conference presentations, and various stakeholder engagement activities. Show less
Background: An increased risk of stroke in patients with migraine has been primarily found for women. The sex-dependent mechanisms underlying the migraine-stroke association, however, remain... Show moreBackground: An increased risk of stroke in patients with migraine has been primarily found for women. The sex-dependent mechanisms underlying the migraine-stroke association, however, remain unknown. This study aims to explore these sex differences to improve our understanding of pathophysiological mechanisms behind the migraine-stroke association.Methods: We included 2,492 patients with ischemic stroke from the prospective multicenter Dutch Parelsnoer Institute Initiative study, 425 (17%) of whom had a history of migraine. Cardiovascular risk profile, stroke cause (TOAST classification), and outcome [modified Rankin scale (mRS) at 3 months] were compared with both sexes between patients with and without migraine.Results: A history of migraine was not associated with sex differences in the prevalence of conventional cardiovascular risk factors. Women with migraine had an increased risk of stroke at young age (onset < 50 years) compared with women without migraine (RR: 1.7; 95% CI: 1.3-2.3). Men with migraine tended to have more often stroke in the TOAST category other determined etiology (RR: 1.7; 95% CI: 1.0-2.7) in comparison with men without migraine, whereas this increase was not found in women with migraine. Stroke outcome was similar for women with or without migraine (mRS >= 3 RR 1.1; 95% CI 0.7-1.5), whereas men seemed to have a higher risk of poor outcome compared with their counterparts without migraine (mRS >= 3 RR: 1.5; 95% CI: 1.0-2.1).Conclusion: Our results indicate possible sex differences in the pathophysiology underlying the migraine-stroke association, which are unrelated to conventional cardiovascular risk factors. Further research in larger cohorts is needed to validate these findings. Show less
Background The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied.Methods We randomly assigned patients within 6 hours after... Show moreBackground The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied.Methods We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days.Results A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12).Conclusions Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.)Endovascular Therapy for Basilar-Artery Stroke In a randomized trial involving 300 patients with basilar-artery stroke, endovascular thrombectomy was not significantly different from medical therapy with respect to a favorable functional outcome (modified Rankin scale score of 0 to 3) at 90 days, but a clinically significant benefit could not be excluded. Show less
Health-care professionals and researchers have a legal and ethical responsibility to inform patients before carrying out diagnostic tests or treatment interventions as part of a clinical study.... Show moreHealth-care professionals and researchers have a legal and ethical responsibility to inform patients before carrying out diagnostic tests or treatment interventions as part of a clinical study. Interventional research in emergency situations can involve patients with some degree of acute cognitive impairment, as is regularly the case in traumatic brain injury and ischaemic stroke. These patients or their proxies are often unable to provide informed consent within narrow therapeutic time windows. International regulations and national laws are criticised for being inconclusive or restrictive in providing solutions. Currently accepted consent alternatives are deferred consent, exception from consent, or waiver of consent. However, these alternatives appear under-utilised despite being ethically permissible, socially acceptable, and regulatorily compliant. We anticipate that, when the requirements for medical urgency are properly balanced with legal and ethical conduct, the increased use of these alternatives has the potential to improve the efficiency and quality of future emergency interventional studies in patients with an inability to provide informed consent. Show less
Background and Purpose:Optimal blood pressure (BP) targets before endovascular treatment (EVT) for acute ischemic stroke are unknown. We aimed to assess the relation between admission BP and... Show moreBackground and Purpose:Optimal blood pressure (BP) targets before endovascular treatment (EVT) for acute ischemic stroke are unknown. We aimed to assess the relation between admission BP and clinical outcomes and successful reperfusion after EVT.Methods:We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, an observational, prospective, nationwide cohort study of patients with ischemic stroke treated with EVT in routine clinical practice in the Netherlands. Baseline systolic BP (SBP) and diastolic BP (DBP) were recorded on admission. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2B-3), symptomatic intracranial hemorrhage, and 90-day mortality. Multivariable logistic and linear regression were used to assess the associations of SBP and DBP with outcomes. The relations between BPs and outcomes were tested for nonlinearity. Parameter estimates were calculated per 10 mm Hg increase or decrease in BP.Results:We included 3180 patients treated with EVT between March 2014 and November 2017. The relations between admission SBP and DBP with 90-day modified Rankin Scale scores and mortality were J-shaped, with inflection points around 150 and 81 mm Hg, respectively. An increase in SBP above 150 mm Hg was associated with poor functional outcome (adjusted common odds ratio, 1.09 [95% CI, 1.04-1.15]) and mortality at 90 days (adjusted odds ratio, 1.09 [95% CI, 1.03-1.16]). Following linear relationships, higher SBP was associated with a lower probability of successful reperfusion (adjusted odds ratio, 0.97 [95% CI, 0.94-0.99]) and with the occurrence of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.06 [95% CI, 0.99-1.13]). Results for DBP were largely similar.Conclusions:In patients with acute ischemic stroke treated with EVT, higher admission BP is associated with lower probability of successful reperfusion and with poor clinical outcomes. Further research is needed to investigate whether these patients benefit from BP reduction before EVT. Show less
In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest... Show moreIn recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case-control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67-75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62-80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 mu M, Wilcoxonp < 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77,p = 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections. Show less
BackgroundIn stroke studies, ordinal logistic regression (OLR) is often used to analyze outcome on the modified Rankin Scale (mRS), whereas the non-parametric Mann-Whitney measure of superiority ... Show moreBackgroundIn stroke studies, ordinal logistic regression (OLR) is often used to analyze outcome on the modified Rankin Scale (mRS), whereas the non-parametric Mann-Whitney measure of superiority (MWS) has also been suggested. It is unclear how these perform comparatively when confounding adjustment is warranted.AimsOur aim is to quantify the performance of OLR and MWS in different confounding variable settings.MethodsWe set up a simulation study with three different scenarios; (1) dichotomous confounding variables, (2) continuous confounding variables, and (3) confounding variable settings mimicking a study on functional outcome after stroke. We compared adjusted ordinal logistic regression (aOLR) and stratified Mann-Whitney measure of superiority (sMWS), and also used propensity scores to stratify the MWS (psMWS). For comparability, OLR estimates were transformed to a MWS. We report bias, the percentage of runs that produced a point estimate deviating by more than 0.05 points (point estimate variation), and the coverage probability.ResultsIn scenario 1, there was no bias in both sMWS and aOLR, with similar point estimate variation and coverage probabilities. In scenario 2, sMWS resulted in more bias (0.04 versus 0.00), and higher point estimate variation (41.6% versus 3.3%), whereas coverage probabilities were similar. In scenario 3, there was no bias in both methods, point estimate variation was higher in the sMWS (6.7%) versus aOLR (1.1%), and coverage probabilities were 0.98 (sMWS) versus 0.95 (aOLR). With psMWS, bias remained 0.00, with less point estimate variation (1.5%) and a coverage probability of 0.95.ConclusionsThe bias of both adjustment methods was similar in our stroke simulation scenario, and the higher point estimate variation in the MWS improved with propensity score based stratification. The stratified MWS is a valid alternative for adjusted OLR only when the ratio of number of strata versus number of observations is relatively low, but propensity score based stratification extends the application range of the MWS. Show less
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... Show moreBackground: 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 this initiative, the so-called Parelsnoer Institute-Cerebrovascular Accident Study Group, clinical data, imaging, and biomaterials of patients with stroke are prospectively and uniformly collected. We compared the proportions of posterior stroke location in patients with a cardiac stroke source with those with another stroke etiology and calculated risk ratios (RR) with corresponding 95% CI with Poisson regression analyses. To assess which patient or disease characteristics were most strongly associated with a cardiac etiology in patients with ischemic stroke, we performed a stepwise backward regression analysis. Results: For the primary aim, 1,428 patients were eligible for analyses. The proportion of patients with a posterior stroke location among patients with a cardiac origin of their stroke (28%) did not differ statistically significant to those with another origin (25%), age and sex adjusted RR 1.16; 95% CI 0.96-1.41. For the secondary aim, 1,955 patients were eligible for analyses. No recent history of smoking, no hyperlipidemia, coronary artery disease, a higher age, and a higher National Institutes of Health Stroke Scale (NIHSS) score were associated with a cardiac etiology of ischemic stroke. Conclusions: We could not confirm our hypothesis that thromboembolic stroke localized in the posterior circulation is associated with a cardioembolic source of ischemic stroke, and therefore posterior stroke localization on itself does not necessitate additional cardiac examination. The lack of determinants of atherosclerosis, for example, no recent history of smoking and no hyperlipidemia, coronary artery disease, a higher age, and a higher NIHSS score are stronger risk factors for a cardiac source of ischemic stroke. Show less
