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In-stent restenosis (ISR) represents a major complication after stenting of intracranial artery stenosis (ICAS). Biomarkers derived from routine blood sampling including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) have been associated with progressive atherosclerosis. We investigated the role of CRP, NLR, PLR and MPV on the development of intracranial ISR and recurrent stroke risk. We retrospectively included all patients who had undergone stenting of symptomatic ICAS at our university hospital between 2005 and 2016. ISR (≥ 50% stenosis) was diagnosed by regular Duplex sonography follow-up studies and confirmed by digital subtraction angiography or computed tomography angiography (mean follow-up duration: 5 years). Laboratory parameters were documented before stenting, at the time of restenosis and at last clinical follow-up. Of 115 patients (mean age: 73 ± 13 years; female: 34%), 38 (33%) developed ISR. The assessed laboratory parameters did not differ between patients with ISR and those without (p > 0.1). While ISR was associated with the occurrence of recurrent ischemic stroke (p = 0.003), CRP, NLR, PLR and MPV were not predictive of such events (p > 0.1). Investigated blood biomarkers of progressive atherosclerosis were not predictive for the occurrence of ISR or recurrent ischemic stroke after ICAS stenting during a 5-year follow-up.

Background and purposeCerebral hyperperfusion has been related to the risk of intracranial hemorrhage (ICH) in stroke patients after vessel recanalization therapy. We hypothesized that after successful mechanical thrombectomy for acute anterior circulation stroke, hemodynamics detectable by transcranial Duplex (TCD) sonography would vary, and that increased blood flow velocities would be associated with ICH.MethodsWe retrospectively identified all ischemic stroke patients with successful endovascular recanalization for anterior circulation vessel occlusion (Thrombolysis in Cerebral Infarction 2b–3) between 2010 and 2017. We reviewed their postinterventional TCD examinations for mean blood flow (MBF) velocities of the recanalized and contralateral middle cerebral artery (MCA) and searched for an association with postinterventional ICH and clinical outcome.Results123 stroke patients (mean age 63±14 years, 40% women) with successful anterior circulation thrombectomy were analyzed. Of those, 18 patients had postinterventional ICH. ICH patients had an increased MCA MBF velocity index (=MBF velocity of the recanalized divided by the contralateral MCA) compared with non-ICH patients (1.32±0.39 vs 1.02±0.32, P<0.001). In multivariate analysis, a higher MCA MBF velocity index was associated with postinterventional ICH and poor 90 day outcome.ConclusionsA high MCA MBF velocity index on TCD after successful recanalization therapy for anterior circulation stroke indicates a risk for postinterventional ICH and worse prognosis.

Background: Cortical superficial siderosis (CSS) is a neuroimaging marker of cerebral amyloid angiopathy and has been associated with a high risk for early subsequent major intracranial hemorrhage (ICH). Therefore, many experts recommend withholding of antithrombotic medication to patients with CSS. In this study, we sought to investigate the prevalence of CSS and the associated risk of ICH in the setting of intravenous thrombolysis (IVT) for ischemic stroke. Methods: We retrospectively searched the medical documentation system of our primary and tertiary care university clinic for all patients with ischemic stroke that received IVT from 2009 to December 2014. All available imaging data were reviewed in a standardized manner and blinded to any clinical data for the presence of CSS and ICH. CSS was defined as linear signal loss along the cerebral cortex on gradient echo T2*-weighted sequences. A stroke neurologist, who was blinded to the neuroimaging data, extracted the corresponding clinical data including follow-up information. Results: We identified 298 patients that received IVT and had undergone brain MRI (mean age 67.6 ± 12.6 years, 59.4% male). Cerebral MRI was performed in 116 patients (38.9%) before and in 182 patients (61.1%) after IVT (median time from stroke symptom onset to MRI: 1 day; range 0-7 days). Only 3 patients (2 females and 1 male aged 90, 76 and 73 years, respectively) had CSS (1%). All of them had a middle cerebral artery (MCA) stroke with a corresponding vessel occlusion. The 76-year-old female patient had extensive CSS and numerous cerebral microbleeds and received another IVT treatment for recurrent MCA stroke 8 months after the first event. After both IVTs, she had clinically asymptomatic small ICH outside the ischemic infarct and distant from CSS. The 2 other patients had only mild to moderate CSS and did not experience any ICH on postthrombolytic imaging. Conclusions: The prevalence of CSS in a clinical cohort of stroke patients that received IVT was low and thus does not appear to pose a substantial risk for symptomatic ICH although this may occur in individual patients. However, such analysis also needs to be extended to the very old stroke patients in whom IVT is increasingly used.

Background: Patients with transient ischemic attack (TIA) and stroke have an increased risk for subsequent cardiac events including myocardial infarction (MI), which might be associated with a worse clinical outcome. Rapid identification of stroke patients at higher risk for MI might foster intensified cardiac monitoring or certain therapeutic strategies. However, information regarding acute MI as a complication of stroke in the very acute phase is limited. Moreover, there are no systematic data on the occurrence of MI following intracerebral hematoma. We thus aimed to assess the frequency, clinical characteristics and short-term outcome of patients suffering from acute MI in the stroke unit setting. Methods: We analyzed 46,603 patients from 32 Austrian stroke units enrolled in the prospective Austrian Stroke Unit Registry because of TIA/acute stroke over a 6-year period (January 1, 2007 to January 13, 2013). A total of 41,619 patients (89.3%) had been treated for TIA/ischemic stroke and 4,984 (10.7%) for primary intracerebral hemorrhage (ICH). Acute MI was defined according to clinical evaluation, ECG findings and laboratory assessments. Patients with evidence for MI preceding the cerebrovascular event were not considered. Results: Overall, 421 patients (1%) with TIA/ischemic stroke and 17 patients (0.3%) with ICH suffered from MI during stroke unit treatment for a median duration of 3 days. Patients with TIA/ischemic stroke and MI were significantly older, clinically more severely affected and had more frequently vascular risk factors, atrial fibrillation and previous MI. Total anterior circulation and left hemispheric stroke syndromes were more often observed in MI patients. Patients with MI not only suffered from worse short-term outcome including a higher mortality (14.5 vs. 2%; p < 0.001) at stroke unit discharge, but also acquired more stroke complications like progressive stroke and pneumonia. Multivariate analyses identified previous MI and stroke severity at admission (according to the National Institutes of Health and Stroke Scale score) as factors independently associated with the occurrence of MI on the stroke unit. Conclusions: While quite rare in the acute phase after stroke, MI is associated with a poor short-term outcome including a higher mortality. Patients with previous MI and severe stroke syndromes appear to be at particular risk for MI as an early complication in the stroke unit setting. Further studies are needed to determine whether increased vigilance and prolonged (cardiac) monitoring or certain therapeutic approaches could improve the outcome in these high-risk patients.

Stroke thrombolysis with alteplase is currently recommended 0–4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0–1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15–2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23–76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81–2·96, p=0·66). Patients with ischaemic stroke 4·5–9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. None.

The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50–85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6–60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0–5·8) with CEA plus BMT, 4·4% (2·2–8·6) with CAS plus BMT, and 3·1% (1·0–9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22–3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41–5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Stroke risk is increased in cancer patients and cancer activity has been claimed to play a role in the development of ischaemic stroke (IS). We wanted to further test these assumptions and to explore the impact of such relation on short-term prognosis. We identified all IS patients that were admitted to the neurological department of our primary and tertiary care university hospital between 2008 and 2014 ( n  = 4918) and reviewed their medical records for an additional diagnosis of cancer. Cancer patients were categorized into those with “active cancer” (AC: recurrent malignant tumour, metastases, ongoing chemo-/radiotherapy) and “non-active cancer” (NAC). We compared demographic, clinical and neuroimaging features of both patient groups and assessed their association with in-hospital mortality. 300 IS patients with known cancer were identified (AC: n  = 73; NAC: n  = 227). IS patients with AC were significantly younger (70.3 ± 10.6 vs. 74.9 ± 9.9 years), had more severe strokes at admission (NIHSS: median 5 vs. 3), more frequently cryptogenic strokes (50.7 vs. 32.5 %) and more often infarcts in multiple vascular territories of the brain (26 vs. 5.2 %) compared to IS patients with NAC. In-hospital mortality was significantly higher in AC patients (21.9 vs. 6.2 %). Multivariate analysis identified AC (odds ratio [OR] 3.70, 95 % confidence interval [CI] 1.50–9.30), NIHSS at admission (OR 1.10, CI 1.10–1.20) and C-reactive protein level (OR 1.01, CI 1.00–1.02) as factors significantly and independently associated with in-hospital death. Our findings support a direct role of AC in the pathogenesis and prognosis of acute IS. This needs to be considered in the management and counselling of such patients.

Background and purpose Clinical outcome after mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke is influenced by the intracerebral collateral status. We tested the hypothesis that patients with preexisting ipsilateral extracranial carotid artery stenosis (CAS) would have a better collateral status compared to non-CAS patients. Additionally, we evaluated MT-related adverse events and outcome for both groups. Methods Over a 7-year period, we identified all consecutive anterior circulation MT patients (excluding extracranial carotid artery occlusion and dissection). Patients were grouped into those with CAS ≥ 50% according to the NASCET criteria and those without significant carotid stenosis (non-CAS). Collateral status was rated on pre-treatment CT- or MR-angiography according to the Tan Score. Furthermore, we assessed postinterventional infarct size, adverse events and functional outcome at 90 days. Results We studied 281 LVO stroke patients, comprising 46 (16.4%) with underlying CAS ≥ 50%. Compared to non-CAS stroke patients ( n  = 235), patients with CAS-related stroke more often had favorable collaterals (76.1% vs. 46.0%). Recanalization rates were comparable between both groups. LVO stroke patients with underlying CAS more frequently had adverse events after MT (19.6% vs. 6.4%). Preexisting CAS was an independent predictor for favorable collateral status in multivariable models (Odds ratio: 3.3, p  = 0.002), but post-interventional infarct size and functional 90-day outcome were not different between CAS and non-CAS patients. Conclusions Preexisting CAS ≥ 50% was associated with better collateral status in LVO stroke patients. However, functional 90-day outcome was independent from CAS, which could be related to a higher rate of adverse events.

Background and purposeWith aging population, there is an increase of atrial fibrillation (AF) and other vascular risk factors. We investigated trends in stroke severity at hospital admission with respect to AF and other risk factors in a prospective national stroke registry from 2005 to 2020.MethodsData from the prospective Austrian Stroke Unit Registry were used to study demographic and clinical factors associated with the change in admission stroke severity over years. Time trends in admission stroke severity of patients with pre-stroke modified Rankin Score ≤ 3 were investigated with respect to clinical variables and predefined age groups 18–54, 55–64, 65–74, 75–84 and ≥ 85 years. Time trends were studied using robust generalized linear models assuming normal distribution with a log link. Stroke severity on admission was assessed according to the National Institutes of Health Stroke Scale Score (NIHSS).ResultsIn total, 140,312 patients with acute ischemic stroke were included in the analysis. Within the study period, mean patients’ age increased from 70 to 72 years (p < 0.001) and median NIHSS at admission decreased from 4 to 3 (p < 0.001). The frequency of AF increased from 25 to 32% (p < 0.001). The decrease in median admission NIHSS was evident in all relevant subgroups but more pronounced in patients with risk factors including AF, diabetes, hypercholesterolemia, smoking, elderly patients and those with pre-stroke disability.ConclusionDespite an aging population and generally increasing AF frequency, we observed a consistent trend towards less disabling strokes on admission.

Background We examined the influence of periprocedural blood pressure (BP), especially critical BP drops, on 3-month functional outcome in stroke patients undergoing mechanical thrombectomy (MT) under general anaesthesia (GA). Methods We screened all patients with anterior circulation large vessel occlusion receiving MT under GA at our centre from January 2011 to June 2016 and selected those who had continuous invasive periinterventional BP monitoring. Clinical and radiological data were prospectively collected as part of an ongoing cohort study, monitoring data were extracted from electronic anaesthesia records. We used uni- and multivariable regression to investigate the association of BP values with unfavourable outcome, defined as modified Rankin Scale scores 3–6 3 months post-stroke. Results 115 patients were included in this study (mean age 65.3 ± 13.0 years, 55.7% male). Periinterventional systolic, diastolic, and mean arterial BP (MAP) values averaged across MT had no effect on outcome. However, single BP drops were related to unfavourable outcome, with absolute MAP drops showing the highest association compared to both systolic and relative BP drops (with reference to pre-interventional values). The BP value with the strongest association with unfavourable outcome was identified as an MAP ever < 60 mmHg ( p  = 0.01) with a pronounced effect in patients with poor collaterals. An MAP < 60 mmHg remained independently associated with poor functional outcome in multivariable analysis ( p  < 0.01). Conclusions For patients undergoing MT under GA, single MAP drops < 60 mmHg are independently related to unfavourable 3-month outcome. Therefore, every effort should be made to prevent periinterventional hypotensive episodes, especially below this threshold.