Showing papers in "Cerebrovascular Diseases in 2020"
TL;DR: This work aims to provide a systematic literature review and prescribe a single drug to treat multiple sclerosis in patients with a history of atypical central giant cell granuloma.
Abstract: aStroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, ON, Canada; bDepartment of Neurology, Universidade Federal Fluminense and Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, Brazil; cDepartment of Neurology, University of Kentucky School of Medicine, Lexington, KY, USA; dDepartment of Neurology and Radiology, Harvard School of Medicine and Takeda Pharmaceutical Company Limited, Cambridge, MA, USA; eNeurovascular Imaging Research Core and UCLA Stroke Center, Department of Neurology, University of California, Los Angeles, CA, USA; fDepartment of Neurology, Emory University, Atlanta, GA, USA; gSchool of Medicine, Universidad Espíritu Santo, Samborondón, Ecuador; hMedical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA, Australia; iRaffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore Received: June 5, 2020 Accepted: June 22, 2020 Published online: July 20, 2020
145 citations
TL;DR: Compared to dEVT, IVT + EVT associates with better functional outcome and lower mortality, and post hoc data from RCTs point to substantial equivalence of reperfusion strategies.
Abstract: Background and Aim: The risk/benefit profile of intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) in acute ischemic stroke is still unclear. We provide a systematic review and meta-analysis including studies comparing direct EVT (dEVT) vs. bridging treatment (IVT + EVT), defining the impact of treatment timing and eligibility to IVT on functional status and mortality. Methods: Protocol was registered with PROSPERO (CRD42019135915) and followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials (RCTs), retrospective, and prospective studies comparing IVT + EVT vs. dEVT in adults (≥18) with acute ischemic stroke. Primary endpoint was functional independence at 90 days (modified Rankin Scale 2a), (ii) mortality, and (iii) symptomatic intracranial hemorrhage (sICH). Subgroup analysis was performed according to study type, eligibility to IVT, and onset-to-groin timing (OGT), stratifying studies for similar OGT. ORs for endpoints were pooled with meta-analysis and compared between reperfusion strategies. Results: Overall, 35 studies were included (n = 9,117). No significant differences emerged comparing patients undergoing dEVT and bridging treatment for gender, hypertension, diabetes, National Institute of Health Stroke Scale score at admission. Regarding primary endpoint, IVT + EVT was superior to dEVT (OR 1.44, 95% CI 1.22–1.69, p < 0.001, pheterogeneity<0.001), with number needed to treat being 18 in favor of IVT + EVT. Results were confirmed in studies with similar OGT (OR 1.66; 95% CI 1.21–2.28), shorter OGT for IVT + EVT (OR 1.53, 95% CI 1.27–1.85), and independently from IVT eligibility (OR 1.53, 95% CI 1.29–1.82). Mortality at 90 days was higher in dEVT (OR 1.38; 95% CI 1.09–1.75), but no significant difference was noted for sICH. However, considering data from RCT only, reperfusion strategies had similar primary (OR 0.91, 95% CI 0.6–1.39) and secondary endpoints. Differences in age and clinical severity across groups were unrelated to the primary endpoint. Conclusions: Compared to dEVT, IVT + EVT associates with better functional outcome and lower mortality. Post hoc data from RCTs point to substantial equivalence of reperfusion strategies. Therefore, an adequately powered RCTs comparing dEVT versus IVT + EVT are warranted.
28 citations
TL;DR: Long-term complications occur frequently after SAH and are associated with an impairment of functional and social outcomes and treatment strategies specifically targeting these complications, including preventive aspects, are warranted.
Abstract: BACKGROUND While the short-term clinical outcome of patients with subarachnoid hemorrhage (SAH) is well described, there are limited data on long-term complications and their impact on social reintegration. This study aimed to assess the frequency of complications post-SAH and to investigate whether these complications attribute to functional and self-reported outcomes as well as the ability to return to work in these patients. METHODS This retrospective single-center study included patients with atraumatic SAH over a 5-year period at a tertiary care center. Patients received a clinical follow-up for 12 months. In addition to demographics, imaging data, and parameters of acute treatment, the rate and extent of long-term complications after SAH were recorded. The functional outcome was assessed using the modified Rankin Scale (mRS; favorable outcome defined as mRS = 0-2). Further outcomes comprised self-reported subjective health measured by the EQ-5D and return to work for SAH patients with appropriate age. Multivariable analyses including in-hospital parameters and long-term complications were conducted to identify parameters independently associated with outcomes in SAH survivors. RESULTS This study cohort consisted of 505 SAH patients of whom 405 survived the follow-up period of 12 months (i.e., mortality rate of 19.8%). Outcome data were available in 359/405 (88.6%) patients surviving SAH. At 12 months, a favorable functional outcome was achieved in 287/359 (79.9%) and 145/251 (57.8%) SAH patients returned to work. The rates of post-acute complications were headache (32.3%), chronic hydrocephalus requiring permanent ventriculoperitoneal shunting (VP shunt 25.4%) and epileptic seizures (9.5%). Despite patient's and clinical characteristics, both presence of epilepsy and need for VP shunt were independently and negatively associated with a favorable functional outcome (epilepsy: adjusted odds ratio [aOR] (95% confidence interval [95% CI]): 0.125 [0.050-0.315]; VP shunt: 0.279 [0.132-0.588]; both p < 0.001) as well as with return to work (aOR [95% CI]: epilepsy 0.195 [0.065-0.584], p = 0.003; VP shunt 0.412 [0.188-0.903], p = 0.027). Multivariable analyses revealed presence of headache, VP shunt, or epilepsy to be significantly related to subjective health impairment (aOR [95% CI]: headache 0.248 [0.143-0.430]; epilepsy 0.223 [0.085-0.585]; VP shunt 0.434 [0.231-0.816]; all p < 0.01). CONCLUSIONS Long-term complications occur frequently after SAH and are associated with an impairment of functional and social outcomes. Further studies are warranted to investigate if treatment strategies specifically targeting these complications, including preventive aspects, may improve the outcomes after SAH.
26 citations
TL;DR: It is demonstrated that overexpressed miR-384-5p targeting DLL4 could stimulate proliferation and angiogenesis, while inhibiting apoptosis of EPCs in mice with cerebral ischemic stroke through the Notch signaling pathway.
Abstract: Background MicroRNAs (miRs) have a crucial regulatory role in endothelial cell function and tumor angiogenesis by inhibiting the expressions of their target genes. The participation of microRNA-384-5p (miR-384-5p) has been prominently reported in various ischemia-induced diseases such as myocardial ischemia and atherosclerosis. Hence, the present study aimed at exploring the effect of miR-384-5p on proliferation, apoptosis, and angiogenesis of endothelial progenitor cells (EPCs) in cerebral ischemic stroke and investigating the associated underlying mechanism. Methods A middle cerebral artery occlusion (MCAO) mouse model was established, with determination of the expression of cluster of differentiation 31 (CD31) and vascular endothelial growth factor (VEGF) proteins. Next, the MCAO mice and EPCs separated from MCAO mice were injected or transfected with mimics or inhibitors of miR-384-5p, or small interference RNA Delta-likeligand 4 (si-DLL4) in order to evaluate their effect on brain infarct size, cell proliferation, apoptosis, and angiogenesis. The relationship among miR-384-5p, DLL4, and the Notch signaling pathway was then verified by a series of experiments. Results In MCAO mice, an increased brain infarct size and cell apoptosis in brain tissues were evident, with decreased expression of miR-384-5p, VEGF, and CD31, as well as increased DLL4 expression. After miR-384-5p mimic or si-DLL4 treatment, the brain infarct size and cell apoptosis in the brain tissues were reduced in compliance with an increased expression of VEGF and CD31. Our findings demonstrated that miR-384-5p negatively regulated the expression of DLL4, which further downregulated the Notch signaling pathway. When miR-384-5p was overexpressed or DLL4 silenced, the cell proliferation and angiogenesis of EPCs were promoted and cell apoptosis was inhibited. Conclusions Our study demonstrated that overexpressed miR-384-5p targeting DLL4 could stimulate proliferation and angiogenesis, while inhibiting apoptosis of EPCs in mice with cerebral ischemic stroke through the Notch signaling pathway.
23 citations
TL;DR: LAVi is associated with new-onset atrial fibrillation and stroke recurrence in ESUS patients and may be a better surrogate of atrial cardiopathy.
Abstract: Introduction It is unclear which surrogate of atrial cardiopathy best predicts the risk of developing a recurrent ischemic stroke in embolic stroke of undetermined source (ESUS) Left atrial diameter (LAD) and LAD index (LADi) are often used as markers of left atrial enlargement in current ESUS research, but left atrial volume index (LAVi) has been found to be a better predictor of cardiovascular outcomes in other patient populations Objective We aim to compare the performance of LAVi, LAD, and LADi in predicting the development of new-onset atrial fibrillation (AF) and stroke recurrence in ESUS Methods Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF, ischemic stroke recurrence, and a composite outcome of occult AF and stroke recurrence LAVi and LADi were measured by transthoracic echocardiogram; "high" LAVi was defined as ≥35 mL/m2 in accordance with American Society of Echocardiography guidelines Results 185 ischemic stroke patients with ESUS were recruited and followed for a median duration of 21 years Increased LAVi was associated with new-onset AF detection (aOR 108; 95% CI 103-114; p = 0003) and stroke recurrence (aOR 105; 95% CI 101-110; p = 0026) Patients with "high" LAVi had a higher likelihood of developing a composite of AF detection and stroke recurrence (HR 345; 95% CI 155-767; p = 0002) No significant association was observed between LADi and either occult AF or stroke recurrence Conclusions LAVi is associated with new-onset AF and stroke recurrence in ESUS patients and may be a better surrogate of atrial cardiopathy
23 citations
TL;DR: The increased levels of MMP-9, tenascin-C, CRP, thioredoxin, and decreased levels of ADAMTS13 and gelsolin were independent predictors of futile recanalization in AIS patients after recenalization by EVT.
Abstract: BACKGROUND We aimed to identify plasma markers of unfavorable outcomes for patients with acute ischemic stroke (AIS) after recanalization by endovascular thrombectomy (EVT). METHODS From November 2017 to May 2019, we prospectively collected 61 AIS patients due to anterior large vessel occlusion who achieved recanalization by EVT. Plasma samples were obtained between 18 and 24 h after recanalization. Unfavorable outcomes included futile recanalization at 90 days and overall early complications within 7 days after EVT. RESULTS After adjustment for age and initial National Institute of Health Stroke Scale (NIHSS), matrix metalloproteinase-9 (MMP-9), tenascin-C, thioredoxin, ADAMTS13, and gelsolin were independently associated with both futile recanalization and overall early complications significantly (all p < 0.05), while C-reactive protein (CRP) was independently associated with overall early complications (p = 0.031) but at the limit of significance for futile recanalization (p = 0.051). The baseline clinical model (BCM) (including age and initial NIHSS) demonstrated discriminating ability to indicate futile recanalization (area under the curve [AUC] 0.807, 95% confidence interval [CI] 0.693-0.921) and overall early complications (AUC 0.749, 95% CI 0.611-0.887). BCM+MMP-9+thioredoxin enhanced discrimination (AUC 0.908, 95% CI 0.839-0.978, p = 0.043) and reclassification (net reclassification improvement [NRI] 67.2%, p < 0.001) to indicate futile recanalization. With respect to overall early complications, BCM+MMP-9+tenascin-C, BCM+MMP-9+CRP, BCM+MMP-9+ADAMTS13, BCM+tenascin-C+ADAMTS13, and BCM+CRP+ADAMTS13, all improved discrimination (AUC [95% CI]: 0.868 [0.766-0.970], 0.882 [0.773-0.990], 0.886 [0.788-0.984], 0.880 [0.783-0.977], and 0.863 [0.764-0.962], respectively, all p < 0.05 by the DeLong method) and reclassification (NRI 59.1%, 71.8%, 51.1%, 67.4%, and 38.3%, respectively, all p < 0.05). CONCLUSIONS The increased levels of MMP-9, tenascin-C, CRP, thioredoxin, and decreased levels of ADAMTS13 and gelsolin were independent predictors of futile recanalization in AIS patients after recanalization by EVT.
20 citations
TL;DR: Air pollution in winter was found to be associated with hospitalisation for all strokes in a large urban centre in Ireland, and this highlights the need to introduce policy changes to reduce air pollution in all countries.
Abstract: Background The harmful effects of outdoor air pollution on stroke incidence are becoming increasingly recognised. We examined the impact of different air pollutants (PM2.5, PM10, NO2, ozone, and SO2) on admission for all strokes in two Irish urban centres from 2013 to 2017. Methods Using an ecological time series design with Poisson regression models, we analysed daily hospitalisation for all strokes and is-chaemic stroke by residence in Dublin or Cork, with air pollution level monitoring data with a lag of 0-2 days from exposure. Splines of temperature, relative humidity, day of the week, and time were included as confounders. Analysis was also performed across all four seasons. Data are presented as relative risks (RRs) and 95% confidence intervals (95% CI) per interquartile range (IQR) increase in each pollutant. Results There was no significant association between all stroke admission and any individual air pollutant. On seasonal analysis, during winter in the larger urban centre (Dublin), we found an association between all stroke cases and an IQR increase in NO2 (RR 1.035, 95% CI: 1.003-1.069), PM10 (RR 1.032, 95% CI: 1.007-1.057), PM2.5 (RR 1.024, 95% CI: 1.011-1.039), and SO2 (RR 1.035, 95% CI: 1.001-1.071). There was no significant association found in the smaller urban area of Cork. On meta-analysis, there remained a significant association between NO2 (RR 1.013, 95% CI: 1.001-1.024) and PM2.5 (1.009, 95% CI 1.004-1.014) per IQR increase in each. Discussion Short-term air pollution in winter was found to be associated with hospitalisation for all strokes in a large urban centre in Ireland. As Ireland has relatively low air pollution internationally, this highlights the need to introduce policy changes to reduce air pollution in all countries.
20 citations
TL;DR: Irisin could reduce neuronal damage and neurofunctional impairment after I/R injury by downregulating the TLR4/MyD88 and inhibiting NF-κB activation.
Abstract: Background Inflammatory response exerts an important role in ischemia/reperfusion (I/R) injury. TLR4 and myeloid differentiation factor 88 (MyD88) are key components in inflammation and are involved in the cerebral I/R injury. Irisin is a skeletal muscle-derived myokine produced after exercise, which was found to suppress inflammation. In this study, we investigated whether irisin could protect the brain from I/R injury through the TLR4/MyD88 pathway. Methods Male Sprague Dawley rats (20 months, 190 ∼ 240 g) were pretreated with irisin at 10, 50, or 100 mg/kg for consecutive 3 days and then subjected to surgery of middle cerebral artery occlusion or sham operation. Infarct size and neuron loss were measured to evaluate brain damage. The mRNA and protein levels of TLR4 and MyD88 were measured by in situ hybridization and immunohistochemistry, respectively. NF-κB activation was assessed by electrophoretic mobility shift assay. Neurological function was evaluated by neurobehavior score test and passive avoidance test. Results Irisin could reduce neuronal damage and neurofunctional impairment after I/R injury. This effect was mediated by downregulating the TLR4/MyD88 and inhibiting NF-κB activation. Conclusion Irisin plays a beneficial effect in I/R injury through regulating the TLR4/MyD88 pathway.
18 citations
TL;DR: The TEE may help in identifying PFO that are of high risk of cerebrovascular accident, including greater PFO height during a Valsalva maneuver, larger septal excursion distance, concomitant atrial sePTal aneurysm, and large right-to-left shunt are associated with stroke-related PFOs.
Abstract: Introduction: It is still disputable whether specific morphometric features of the patent foramen ovale (PFO) may stratify patients by the related probability that a discovered PFO is incidental or stroke related. Objective: We aimed to determine whether certain morphometrical characteristics of PFO are associated with an increased risk of cerebrovascular accidents, using a meta-analytical approach. Methods: We performed a systematic review of electronic databases for studies that compared morphometric parameters of PFO assessed by transesophageal echocardiography (TEE) in subjects with cryptogenic cerebrovascular accidents (Group 1) and control (Group 2). Data were extracted and pooled into a meta-analysis. Results: A total of 895 patients with PFO were reported (Group 1: 493, Group 2: 402). No difference was found in the PFO channel length (Group 1: 10.8 [8.6–12.9] mm vs. Group 2: 10.4 [9.1–11.7] mm), as well as in PFO height measured at rest (Group 1: 2.4 [1.5–3.3] mm vs. Group 2: 1.8 [1.4–2.2] mm). The PFO height measured during a Valsalva maneuver was larger in Group 1 (3.5 [2.8–4.1] mm) than in Group 2 (1.7 [1.2–2.2] mm). Also, the septal excursion distance was found to be larger in Group 1 (6.4 [5.1–7.8] mm) than in Group 2 (3.1 [1.8–4.4] mm). The risk of cerebrovascular accident was higher in patients with PFO and concomitant septal aneurysm (OR 4.00; 95% CI 2.63–6.09; p < 0.001) and with large right-to-left shunt PFO (OR 3.81; 95% CI 2.21–6.55; p < 0.001), no such relationship was found for the presence of a Eustachian valve or Chiari’s network (OR 1.90; 95% CI 0.90–4.05; p = 0.094). Conclusions: The TEE may help in identifying PFO that are of high risk of cerebrovascular accident. Greater PFO height during a Valsalva maneuver, larger septal excursion distance, concomitant atrial septal aneurysm, and large right-to-left shunt are associated with stroke-related PFOs.
17 citations
TL;DR: Tirofiban is safe in AIS patients with ET and can significantly reduce mortality; preoperative tiroFiban may be effective, but further studies are needed to confirm the efficacy.
Abstract: Objectives Tirofiban is widely used in clinical practice for acute ischemic stroke (AIS). However, whether tirofiban increases the bleeding risk or improves the outcome of AIS patients with endovascular treatment (ET) is unknown. The aim of this meta-analysis is to evaluate the safety and efficacy of tirofiban compared with those without tirofiban in AIS patients receiving ET. Methods Systematic literature search was done in PubMed and EMBASE databases without language or time limitation. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes were recanalization rate and favorable functional outcome. Review Manager 5.3 and Stata Software Package 15.0 were used to perform the meta-analysis. Results Eleven studies with a total of 2,028 patients were included. A total of 704 (34.7%) patients were administrated tirofiban combined with ET. Meta-analysis suggested that tirofiban did not increase the risk of sICH (odds ratio (OR) 1.08; 95% confidence interval (CI) 0.81-1.46; p = 0.59) but significantly decreased mortality (OR 0.68; 95% CI 0.52-0.89; p = 0.005). There was no association between tirofiban and recanalization rate (OR 1.26; 95% CI 0.86-1.82; p = 0.23) or favorable functional outcome (OR 1.21; 95% CI 0.88-1.68; p = 0.24). Subgroup analyses indicated that preoperative tirofiban significantly increase recanalization rate (OR 3.89; 95% CI 1.70-8.93; p = 0.001) and improve favorable functional outcome (OR 2.30; 95% CI 1.15-4.60; p = 0.02). Conclusions Tirofiban is safe in AIS patients with ET and can significantly reduce mortality; preoperative tirofiban may be effective, but further studies are needed to confirm the efficacy.
17 citations
TL;DR: Stroke patients living in rural areas were younger than those living in major cities (75 years, Stroke Audit Data), with aeromedically retrieved Indigenous patients being a decade younger than non-Indigenous patients.
Abstract: Introduction Rural, remote, and Indigenous stroke patients have worse stroke outcomes than urban Australians This may be due to lack of timely access to expert facilities Objectives We aimed to describe the characteristics of patients who underwent aeromedical retrieval for stroke, estimate transfer times, and investigate if flight paths corresponded with the locations of stroke units (SUs) throughout Australia Methods Prospective review of routinely collected Royal Flying Doctor Service (RFDS) data Patients who underwent an RFDS aeromedical retrieval for stroke, July 2014-June 2018 (ICD-10 codes: I60-I69), were included To define the locations of SUs throughout Australia, we accessed data from the 2017 National Stroke Audit The main outcome measures included determining the characteristics of patients with an in-flight diagnosis of stroke, their subsequent pickup and transfer locations, and corresponding SU and imaging capacity Results The RFDS conducted 1,773 stroke aeromedical retrievals, consisting of 1,028 (58%) male and 1,481 (835%) non-Indigenous and 292 (165%) Indigenous patients Indigenous patients were a decade younger, 560 (interquartile range [IQR] 450-640), than non-Indigenous patients, 660 (IQR 540-760) The most common diagnosis was "stroke not specified," reflecting retrieval locations without imaging capability The estimated median time for aeromedical retrieval was 238 min (95% confidence interval: 231-244) Patients were more likely to be transferred to an area with SU and imaging capability (both p Conclusion Stroke patients living in rural areas were younger than those living in major cities (75 years, Stroke Audit Data), with aeromedically retrieved Indigenous patients being a decade younger than non-Indigenous patients The current transfer times are largely outside the time windows for reperfusion methods Future research should aim to facilitate more timely diagnosis and treatment of stroke
TL;DR: High frequency of PACs in cryptogenic stroke may be a strong predictor of AF detected by insertable cardiac monitoring (ICM), and time to the first AF after adjustment for CHADS2 score after index stroke and large left atrial diameter.
Abstract: Objective To determine whether frequent premature atrial contractions (PAC) predict atrial fibrillation (AF) in cryptogenic stroke patients, we analyzed the association between frequent PACs in 24-h Holter electrocardiogram recording and AF detected by insertable cardiac monitoring (ICM). Methods We retrospectively analyzed a database of 66 consecutive patients with cryptogenic stroke who received ICM implantation between October 2016 and March 2018 at 5 stroke centers. We included the follow-up data until June 2018 in this analysis. We defined frequent PACs as the upper quartile of the 66 patients. We analyzed the association of frequent PACs with AF detected by ICM. Results Frequent PACs were defined as >222 PACs per a 24-h period. The proportion of patients with newly detected AF by ICM was higher in patients with frequent PACs than those without (50% [8/16] vs. 22% [11/50], p 100 pg/mL) or serum -N-terminal pro-BNP levels (>300 pg/mL), and large left atrial diameter (≥45 mm). Conclusion High frequency of PACs in cryptogenic stroke may be a strong predictor of AF detected by ICM.
TL;DR: The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA, and adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality.
Abstract: Introduction There are a limited number of studies investigating the relationship between the degree of liver fibrosis and the long-term prognosis, especially ischemic stroke (IS) recurrence, in first-ever IS or transient ischemic attack (TIA). Objective We investigated whether there are differences in the long-term all-cause and cardiovascular mortalities and IS recurrence based on the degree of liver fibrosis in first-ever IS or TIA. Methods This analysis included 2,504 patients with first-ever IS or TIA recruited from a prospective stroke cohort. Liver fibrosis was predicted using the fibrosis-4 (FIB-4) index, and advanced fibrosis was defined as an FIB-4 index of >3.25. Using Cox regression models, we compared the all-cause and cardiovascular mortalities and IS recurrence. As measures for the additive predictive value of the FIB-4 index for prediction of all-cause mortality, the integrated area under the receiver operating characteristic curve (iAUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used. Results There were 231 (9.2%) patients with advanced fibrosis. During a median follow-up of 1.2 years, the cumulative all-cause and cardiovascular mortalities were 6.4 and 1.9%, and IS recurrence was observed in 5.3%. The advanced fibrosis was associated with an increased risk of all-cause mortality (hazard ratio [HR] = 3.98, 95% confidence interval [CI] = 2.40-6.59), cardiovascular mortality (HR = 4.48, 95% CI = 1.59-12.65), and IS recurrence (HR = 1.95, 95% CI = 1.05-3.65). Adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality as measured using the iAUC (from 0.7594 to 0.7729) and for all-cause mortality at 1 year as measured using the NRI (38.6%) and IDI (0.037). Conclusions The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA.
TL;DR: It is suggested that COVID-19 can favor strokes and in general vascular complications, even in milder cases, and the presence of preexisting risk factors could play a determinant role.
Abstract: Background The COVID-19 outbreak is currently the major public health concern worldwide. This infection, caused by the novel coronavirus Sars Cov2, primarily affects respiratory system, but there is increasing evidence of neurologic involvement and cerebrovascular accidents. Case report We present a case of stroke in a 62-year-old COVID-19-positive patient, with multiple vascular risk factors. The patient arrived 1 h after onset of symptoms, was treated with recombinant tissue plasminogen activator (rtPA) with improvement of neurologic deficits, and later developed right foot arterial ischemia (recanalized by balloon catheter angioplasty) and left arm superficial venous thrombosis. A control computed tomography (CT) scan 7 days after onset showed hemorrhagic transformation of ischemic lesion without mass effect. However, respiratory and neurologic conditions improved so that the patient was discharged to rehabilitation. Discussion Until now, few cases of stroke in COVID-19 have been described, mainly in severe forms. This patient had ischemic injuries in different sites as well as venous thrombosis; hence, we speculate that Sars Cov2 could have a direct role in promoting vascular accidents since its receptor ACE2 is a surface protein also expressed by endothelial cells. This case suggests that COVID-19 can favor strokes and in general vascular complications, even in milder cases, and the presence of preexisting risk factors could play a determinant role.
TL;DR: The lack of association between large PVSs and cardiovascular risk factors or risk of stroke indicated a nonvascular pathogenic mechanism underlying large P VSs, suggesting the importance of distinguishing large PVss from lacunes in clinical practice.
Abstract: BACKGROUND AND PURPOSE To compare the risk factors and risk of stroke between lacune and large perivascular spaces (PVSs) in a community-based sample. METHODS Large PVSs were assessed using 3.0T MRI in a population-based cohort consisting of 1,204 participants. The relationship between cardiovascular risk factors, neuroimaging changes, and incidental stroke risk and the presence of lacune or large PVSs was assessed with univariate and multivariable ordinal logistic regression analysis. RESULTS Of the 1,204 study participants (55.7 ± 9.3 years, 37.0% men), a total of 347 large PVSs were detected in 235 (19.5%) subjects, while a total of 219 lacunes were detected in 183 subjects (15.2%). The presence of lacunes was found to be significantly associated with age, male gender, hypertension, and diabetes, whereas only age (p < 0.01) and ApoEe4 carrier status (p < 0.01) were related to the presence of large PVSs. Those who had lacunes detected on MRI at baseline had a significant increased risk of stroke (hazard ratio [HR] 4.68; 95% confidence interval [CI], 1.15-19.07) during the 3-year follow-up independent of age, gender, and other vascular risk factors. However, there was no significant relationship between the presence of large PVSs and incident stroke (HR 3.84; 95% CI, 0.82-18.04). CONCLUSIONS The lack of association between large PVSs and cardiovascular risk factors or risk of stroke indicated a nonvascular pathogenic mechanism underlying large PVSs, suggesting the importance of distinguishing large PVSs from lacunes in clinical practice.
TL;DR: This study does not show any significant association between risk of sICH and poor outcome after IVT for patients on prior statin therapy and the intensity of the stain used.
Abstract: AIM The aim of this was to study the effects of statins and their intensity on symptomatic intracranial hemorrhage (sICH) and outcome after IV thrombolysis (IVT) for acute ischemic stroke (AIS). METHODS We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with IVT for AIS in our center in a 10-year period. Patients were further characterized as any statin users versus non-users on admission to the emergency department. Statins were categorized in high intensity or low intensity statin based on its propensity to reduce lower low-density cholesterol by ≥45% or <45%, respectively. Safety and discharge modified Rankin Score were compared between statin users versus non-users and also between high-intensity versus low-intensity groups. RESULTS A total of 834 patients received IVT for AIS in our center during a 10-year period. Multivariate models were adjusted for age, NIH Stroke Scale at admission, INR, and history of DM and atrial fibrillation. There was no association between odds of sICH and any statin use (OR = 0.52 [0.26-1.03], p = 0.06). In multivariate model, any statin use was not associated with odds of poor outcome (Table 4: OR = 1.01 [0.79-1.55], p = 0.57). There was no significant association between odds of sICH among patients on high-intensity statin compared to low intensity statin (multivariate model OR = 0.39 [0.11-1.40], p = 0.15). There was 47% reduced odds of poor outcome among patients on high-intensity statin as compared to low-intensity statin (OR = 0.53[0.32-0.88] p = 0.01). However, this significant association was lost in the multivariate model (OR = 0.60 [0.35-1.05], p = 0.07). CONCLUSION Our study does not show any significant association between risk of sICH and poor outcome after IVT for patients on prior statin therapy. We also did not find significant association between the risk of sICH and poor outcome after IVT and the intensity of the stain used.
TL;DR: The hypothesis that thromboembolic stroke localized in the posterior circulation is associated with a cardioembolic source of ischemic stroke is not confirmed, and therefore posterior stroke localization on itself does not necessitate additional cardiac examination.
Abstract: 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 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.
TL;DR: It is indicated that TCD-guided BP and intracranial pressure control improved the prognosis of patients with blood flow deceleration and intrACranial hypertension.
Abstract: Objective This study aimed to control blood pressure (BP) under transcranial Doppler (TCD) guidance in patients with anterior circulation acute ischemic stroke after endovascular treatment (EVT) to reduce the incidence of early neurological deterioration (END) and improve neurological prognosis. Methods This prospective randomized controlled study included 95 patients who were randomly divided into a TCD-guided BP control (TBC) group and a non-TCD-guided BP control (NBC) group. The patients were monitored by TCD within 72 h after EVT. In the TBC group, BP decreased, BP increased, or intracranial pressure decreased when TCD showed blood flow acceleration, deceleration, or intracranial hypertension respectively. The BP of the NBC group was controlled according to the guidelines. The incidence of END and the prognosis was compared between the 2 groups. Results TCD identified 18 patients with blood flow acceleration, but the prognosis of the 2 groups was not significantly different. TCD identified 23 patients with blood flow deceleration, and the poor prognosis rate at discharge was lower in the TBC group than in the NBC group (45.5 vs. 91.7%, p = 0.027). TCD identified 34 patients with intracranial hypertension, and the 3-month mortality rate of the TBC group was lower than that of the NBC group (0 vs. 36.8%, p = 0.011). The incidence rates of END and 3-month mortality in the TBC group were lower than those in the NBC group (13.8 vs. 37.5%, p = 0.036; 0 vs. 25.0%, p = 0.012) when TCD parameters were abnormal. Multivariable logistic regression analysis showed that the TBC group (adjusted OR 0.267, 95% CI 0.074-0.955; p = 0.042) was an independent protective factor against the incidence of END when TCD parameters were abnormal. Conclusion These findings indicated that TCD-guided BP and intracranial pressure control improved the prognosis of patients with blood flow deceleration and intracranial hypertension.
TL;DR: Intensive SBP lowering reduced the frequency of hematoma expansion but did not reduce the rate of death or disability in patients with moderate to severe grade ICH.
Abstract: Objective: To study the effect of intensive blood pressure reduction in patients with moderate to severe intracerebral hemorrhage (ICH) within the subjects recruited in Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial Design: Randomized, multicenter, 2 group, open-label clinical trial Setting: A total of 110 sites in the USA, Japan, China, Taiwan, South Korea, and Germany Patients: A total of 1,000 patients underwent randomization from May 2011 till September 2015 Interventions: We analyzed the effect of intensive (goal 110–139 mm Hg) over standard (goal 140–179 mm Hg) systolic blood pressure (SBP) reduction using intravenous nicardipine within 45 h of symptom onset in moderate to severe grade subjects with ICH in a non-prespecified analysis Moderate to severe grade was defined by Glasgow Coma Scale score <13 or baseline National Institutes of Health Stroke Scale score ≥10 or baseline intraparenchymal hemorrhage volume ≥30 mL or presence of intraventricular hemorrhage The primary outcome was death or disability (score 4–6 on the modified Rankin scale) at 3 months after randomization ascertained by a blinded investigator Measurements and Main Results: Of a total of 682 subjects who met the definition of moderate to severe grade (mean age 619 ± 131 years, 625% men) with a mean baseline SBP of 1747 ± 248 mm Hg, the frequency of hematoma expansion was significantly lower among subjects randomized to intensive SBP reduction than among subjects randomized to standard SBP reduction (204 vs 279%, relative risk [RR]: 07; 95% confidence interval [CI]: 055–096) The primary endpoint of death or disability was observed in 525% (170/324) of subjects receiving intensive SBP reduction and 489% (163/333) of subjects receiving standard SBP reduction (RR: 11; 95% CI: 09–12) Conclusions: Intensive SBP lowering reduced the frequency of hematoma expansion but did not reduce the rate of death or disability in patients with moderate to severe grade ICH
TL;DR: Transplantation of hUC-MSCs exerts beneficial effect after SAH, possibly be through inhibiting TGF-β1/Smad2/3 signaling pathway.
Abstract: BACKGROUND Emerging evidence indicates a beneficial effect of mesenchymal stem cell (MSC) transplantation in subarachnoid hemorrhage (SAH). Chronic hydrocephalus is a common complication after SAH, which is associated with subarachnoid fibrosis promoted by transforming growth factor-β1 (TGF-β1). This study investigated the effect of human umbilical cord derived MSCs (hUC-MSCs) with TGF-β1 knockdown on chronic hydrocephalus after SAH. METHODS About 0.5 mL autologous blood was injected into the cerebellomedullaris cistern of 6-week SD rats to establish SAH model. hUC-MSCs or hUC-MSCs carrying TGF-β1 knockdown (1 × 105 cells) were intraventricularly transplanted at 1 day before surgery and at P10. Neurological behavior score and water maze test were performed to assess neurological functions. Hydrocephalus was evaluated by Nissl staining. Concentrations of proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. The levels of TGF-β1, p-Smad2/3, and Smad2/3 were measured using western blotting. RESULTS Intraventricular hUC-MSCs transplantation significantly attenuated SAH-induced chronic hydrocephalus, upregulation of inflammatory cytokines, and behavioral impairment. Knockdown of TGF-β1 in hUC-MSCs enhanced these effects. hUC-MSCs also reduced the upregulation of TGF-β1 levels and Smad2/3 phosphorylation after SAH, and this effect was also enhanced by TGF-β1 knockdown. CONCLUSION Transplantation of hUC-MSCs exerts beneficial effect after SAH, possibly be through inhibiting TGF-β1/Smad2/3 signaling pathway. Knockdown of TGF-β1 in hUC-MSCs enhanced these effects.
TL;DR: This first deployment of an MSU in the UK NHS demonstrated improved triage decision-making for or against hospital admission and admission to the appropriate target ward, thereby reducing pressure on strained A&E departments.
Abstract: Background Acute stroke patients are usually transported to the nearest hospital regardless of their required level of care. This can lead to increased pressure on emergency departments and treatment delay. Objective The aim of the study was to explore the benefit of a mobile stroke unit (MSU) in the UK National Health Service (NHS) for reduction of hospital admissions. Methods Prospective cohort audit observation with dispatch of the MSU in the East of England Ambulance Service area in Southend-on-Sea was conducted. Emergency patients categorized as code stroke and headache were included from June 5, 2018, to December 18, 2018. Rate of avoided admission to the accident and emergency (AaE) department, rate of admission directly to target ward, and stroke management metrics were assessed. Results In 116 MSU-treated patients, the following diagnoses were made: acute stroke, n = 33 (28.4%); transient ischaemic attacks, n = 13 (11.2%); stroke mimics, n = 32 (27.6%); and other conditions, n = 38 (32.8%). Pre-hospital thrombolysis was administered to 8 of 28 (28.6%) ischaemic stroke patients. Pre-hospital diagnosis avoided hospital admission for 29 (25.0%) patients. As hospital treatment was indicated, 35 (30.2%) patients were directly triaged to the stroke unit, 1 patient (0.9%) even directly to the catheter laboratory. Thus, only 50 (43.1%) patients required transfer to the AaE department. Moreover, the MSU enabled thrombolysis with a median dispatch-to-needle time of 42 min (interquartile range, 40-60). Conclusion This first deployment of an MSU in the UK NHS demonstrated improved triage decision-making for or against hospital admission and admission to the appropriate target ward, thereby reducing pressure on strained AaE departments.
TL;DR: The signal intensity of the intracranial major arteries, including the ACA, MCA, and PCA, on preoperative 3D-TOF MRA may identify adult MMD patients at higher risk for CHP after direct revascularization surgery.
Abstract: INTRODUCTION Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is an effective surgical procedure for adult patients with moyamoya disease (MMD) and is known to have the potential to prevent cerebral ischemia and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is one of the serious complications of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the prediction of CHP before revascularization surgery remains challenging. The present study evaluated the diagnostic value of preoperative three-dimensional (3D)-time-of-flight (TOF) magnetic resonance angiography (MRA) for predicting CHP after STA-MCA anastomosis for MMD. MATERIALS AND METHODS The signal intensity of the peripheral portion of the intracranial major arteries, such as the anterior cerebral artery (ACA), MCA, and posterior cerebral artery (PCA) ipsilateral to STA-MCA anastomosis, on preoperative MRA was graded (0-2 in each vessel) according to the ability to visualize each vessel on 97 affected hemispheres in 83 adult MMD patients. Local cerebral blood flow (CBF) at the site of anastomosis was quantitatively measured by N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. Then, we investigated the correlation between the preoperative MRA score and the development of CHP. RESULTS The CHP phenomenon 1 day after STA-MCA anastomosis (local CBF increase over 150% compared with the preoperative value) was evident in 27 patients (27/97 hemispheres; 28%). Among them, 8 (8 hemispheres) developed CHP syndrome. Multivariate analysis revealed that the hemispheric MRA score (0-6), the summed ACA, MCA, and PCA scores for the affected hemisphere, was significantly associated with the development of CHP syndrome (p = 0.011). The hemispheric MRA score was also significantly correlated with the CHP phenomenon, either symptomatic or asymptomatic (p < 0.001). CONCLUSION The signal intensity of the intracranial major arteries, including the ACA, MCA, and PCA, on preoperative 3D-TOF MRA may identify adult MMD patients at higher risk for CHP after direct revascularization surgery.
TL;DR: Severe LA is associated with poor clinical outcome at 3 months in acute stroke patients undergoing MT due to emergent M1 MCA occlusion with good clinical outcome after 3 months as measured with the modified Rankin scale.
Abstract: Background: Severe leukoaraiosis (LA) is an established risk factor for poor outcome after mechanical thrombectomy (MT) for large vessel occlusion stroke. There is uncertainty whether this association also applies to successfully recanalized patients with M1 segment middle cerebral artery (MCA) occlusions. Methods: A retrospective single-centre study of patients with successful reperfusion (thrombolysis in cerebral infarction, TICI 2b or 3) after MT for an M1 MCA occlusion was performed over a 7-year period. LA score (LAS) was assessed using the age-related white matter change scale on pre-interventional brain imaging. Results: A total of 209 patients (median age 75.0 years) were included. LAS was assessed on pre-interventional imaging by computed tomography in 177 (84.7%) patients and magnetic resonance imaging in 32 (15.3%) patients. The median LAS was 1 (IQR 0–8), and severe LA consisted of the top 25 percentile, ranging from 9 to 24. Multivariable analysis demonstrated an association of severe LA (OR 0.32, 95% CI 0.12–0.88, p = 0.023), higher NIHSS on admission (OR 0.89, 95% CI 0.84–0.94, p < 0.001), advanced age (OR 0.97, 95% CI 0.95–1.00, p = 0.039), good leptomeningeal collaterals (OR 3.65, 95% CI 1.46–8.15, p = 0.001), and TICI 3 score (OR 3.26, 95% CI 10.52–7.01) with good clinical outcome after 3 months as measured with the modified Rankin scale. Conclusion: Severe LA is associated with poor clinical outcome at 3 months in acute stroke patients undergoing MT due to emergent M1 MCA occlusion.
TL;DR: DWI-FLAIR mismatch was associated with more moderate outcome and less sICH in the adjusted analysis in patients receiving MT for acute LVO, and could be useful to select patients with unknown onset stroke who are eligible to receive MT for urgent LVO.
Abstract: Background and Purpose: Diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch is an early sign of acute ischemic stroke. DWI-FLAIR mismatch was reported to be valuable to select patients with unknown onset stroke who are eligible to receive intravenous thrombolysis (IVT), but its utility is less studied in patients undergoing mechanical thrombectomy (MT) for acute large vessel occlusion (LVO). We thus investigated the functional outcomes at 90 days between patients with DWI-FLAIR mismatch and those with match who underwent MT for LVO. Methods: We conducted a historical cohort study in consecutive patients who were evaluated by magnetic resonance imaging for suspected stroke at a single center. We enrolled patients with occlusion of internal carotid artery or horizontal or vertical segment of middle cerebral artery who underwent MT within 24 h after they were last known to be well. DWI-FLAIR mismatch was defined when a visible acute ischemic lesion was present on DWI without traceable parenchymal hyperintensity on FLAIR. Image analysis was done by 2 stroke neurologists independently. We estimated the adjusted odds ratio (OR) of DWI-FLAIR mismatch relative to DWI-FLAIR match for moderate outcome defined as modified Rankin Scale (mRS) 0–3, favorable outcome defined as mRS 0–2 and mortality at 90 days after the onset, and symptomatic intracranial hemorrhage (sICH) within 72 h after the onset. Results: Of the 380 patients who received MT, 202 were included. Patients with DWI-FLAIR mismatch (146 [72%]) had significantly higher baseline National Institutes of Health Stroke Scale (median 16 vs. 13, p = 0.01), more transferred-in (78 vs. 63%, p = 0.02), more IVT (45 vs. 18%, p = 0.0003), more cardioembolism (69 vs. 54%, p = 0.03), and shorter onset-to-hospital door times (median 175 vs. 371 min, p < 0.0001) than patients with DWI-FLAIR match. Patients with DWI-FLAIR mismatch had more moderate outcome than those with DWI-FLAIR match (61 vs. 52%, p = 0.24), and the adjusted OR was 3.12 (95% confidence interval [CI]: 1.35–7.19, p = 0.008). sICH within 72 h was less frequent in the DWI-FLAIR mismatch group (10 vs. 20%, p = 0.06), with an adjusted OR of 0.36 (95% CI: 0.13–0.97, p = 0.044). The adjusted ORs for favorable outcome and mortality were 0.87 (95% CI: 0.39–1.94, p = 0.73) and 0.63 (95% CI: 0.20–2.05, p = 0.44), respectively. Conclusions: DWI-FLAIR mismatch was associated with more moderate outcome and less sICH in the adjusted analysis in patients receiving MT for acute LVO. DWI-FLAIR mismatch could be useful to select patients with unknown onset stroke who are eligible to receive MT for acute LVO.
TL;DR: Overexpression of miR-340-5p reversed the influence of ICH on the neurological function score and cerebral water content and inhibited the production of proinflammatory cytokines, which were induced by ICH in vivo.
Abstract: Objective Intracerebral hemorrhage (ICH) is a common cerebrovascular disease. Increasing evidence has documented the crucial role of microRNAs in ICH. The present study aimed to investigate the role and underlying mechanism of miR-340-5p in ICH. Methods The collagenase-induced ICH rat model was established. The neurological function of rats and the cerebral water content of rat brain tissue were measured to assess the brain injury. BV-2 cells were recruited and treated by LPS to mimic ICH-induced inflammatory response. qRT-PCR was used for the measurement of miR-340-5p. The protein levels of TNF-α, IL-6, and IL-1β were detected using ELISA. Luciferase reporter gene assay was performed to confirm the target gene. Results Downregulation of miR-340-5p was detected in the serum of ICH patients and the brain tissues of ICH rats. Overexpression of miR-340-5p reversed the influence of ICH on the neurological function score and cerebral water content and inhibited the production of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), which were induced by ICH in vivo. In in vitro study, levels of TNF-α, IL-6, and IL-1β were significantly enhanced in cells after LPS treatment, but these increases were eliminated by overexpression of miR-340-5p. PDCD4 was a direct target gene of miR-340-5p. Conclusion miR-340-5p protects against brain injury after ICH. miR-340-5p might exert an anti-inflammatory effect during the occurrence of ICH via targeting PDCD4.
TL;DR: Elderly and/or low body weight Japanese patients with previous non-cardioembolic ischemic stroke who received PRA3.75 showed similar results in terms of primary safety endpoint, and a numerically lower incidence of isChemic stroke, myocardial infarction, and death from other vascular causes, compared with those who received CLO50.
Abstract: Introduction: The safety of prasugrel in elderly and/or low body weight Japanese patients with ischemic stroke who have a relatively high bleeding risk with antiplatelet therapy remains unknown. Objective: We aimed to investigate the safety and efficacy of long-term prasugrel monotherapy for stroke prevention compared with clopidogrel in elderly and/or low body weight Japanese patients with non-cardioembolic ischemic stroke. Methods: In this randomized, double-blind, comparative, phase III study, elderly (age ≥75 years) and/or low body weight (≤50 kg) Japanese patients with a previous history of non-cardioembolic ischemic stroke were assigned to a prasugrel 3.75 mg (PRA3.75) group, a prasugrel 2.5 mg (PRA2.5) group, or a clopidogrel 50 mg (CLO50) group and followed up for 48 weeks. The primary safety endpoint was the combined incidence of primary safety events, defined as life-threatening, major, and other clinically relevant bleeding. The efficacy endpoint was a composite of ischemic stroke, myocardial infarction, and death from other vascular causes. Results: A total of 654 patients (age 76.4 ± 7.3 years, body weight 55.6 ± 9.3 kg, women 43.9%) from 74 medical institutions within Japan were enrolled. The combined incidence (95% CI) of primary safety events was 4.2% (1.9–7.8%), 1.9% (0.5–4.7%), and 3.6% (1.6–6.9%) in the PRA3.75 group (n = 216), PRA2.5 group (n = 215), and CLO50 group (n = 223), respectively (hazard ratios [HR] PRA3.75/CLO50, 1.13 [0.44–2.93]; PRA2.5/CLO50, 0.51 [0.15–1.69]). The incidences of bleeding leading to treatment discontinuation (95% CI) were 2.3% (0.8–5.3%), 0.9% (0.1–3.3%), and 2.2% (0.7–5.2%) in the PRA3.75, PRA2.5, and CLO50 groups, respectively (HRs PRA3.75/CLO50, 1.01 [0.29–3.48]; PRA2.5/CLO50, 0.41 [0.08–2.12]). There was no significant difference in all bleeding events between groups. The incidence of ischemic stroke, myocardial infarction, and death from other vascular causes was lower, but not significantly so, in patients treated with prasugrel than in patients treated with clopidogrel: PRA3.75, 0.0% (0/216); PRA2.5, 3.3% (7/215); and CLO50, 3.6% (8/223; HRs PRA3.75/CLO50, 0.00 [0.00–0.00]; PRA2.5/CLO50, 0.90 [0.32–2.47]). Conclusions: Elderly and/or low body weight Japanese patients with previous non-cardioembolic ischemic stroke who received PRA3.75 showed similar results in terms of primary safety endpoint, and a numerically lower incidence of ischemic stroke, myocardial infarction, and death from other vascular causes, compared with those who received CLO50.
TL;DR: Wang et al. as mentioned in this paper developed a predictive model based on computed tomography (CT) markers in an Intracerebral Hemorrhage (ICH) cohort and validated it in another cohort.
Abstract: Introduction Intracerebral hemorrhage (ICH) is the most fatal type of stroke worldwide. Herein, we aim to develop a predictive model based on computed tomography (CT) markers in an ICH cohort and validate it in another cohort. Methods This retrospective observational cohort study was conducted in 3 medical centers in China. The values of CT markers, including hypodensities, hematoma density, blend sign, black hole sign, island sign, midline shift, baseline hematoma volume, and satellite sign, in predicting poor outcome were analyzed by logistic regression analysis. A nomogram was developed based on the results of multivariate logistic regression analysis in development cohort. Area under curve (AUC) and calibration plot were used to assess the accuracy of nomogram in this development cohort and validate in another cohort. Results A total of 1,498 patients were included in this study. Multivariate logistic regression analysis indicated that hypodensities, black hole sign, island sign, midline shift, and baseline hematoma volume were independently associated with poor outcome in development cohort. The AUC was 0.75 (95% confidence interval [CI]: 0.73-0.76) in the internal validation with development cohort and 0.74 (95% CI: 0.72-0.75) in the external validation with validation cohort. The calibration plot in development and validation cohort indicated that the nomogram was well calibrated. Conclusions CT markers of hypodensities, black hole sign, and island sign might predict poor outcome of ICH patients within 90 days.
TL;DR: Higher prestroke PA was associated with a better cognitive performance as measured by the Symbol Digit Modalities Test at 1 and 6 months poststroke, and this association remained at 6 months.
Abstract: Introduction Physical activity (PA) is associated with a lower risk of stroke and stroke mortality as well as a favorable stroke outcome. PA may also prevent general cognitive decline. Poststroke cognitive impairment is both common and disabling, and focusing on all possible preventive measures is important. Studies on the effect of PA on poststroke cognitive performance are sparse, however. We therefore aimed to examine the association between prestroke PA and poststroke cognitive performance. Methods We studied the correlation between prestroke PA and poststroke cognitive performance in a prespecified analysis in The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS) trial. We used the Physical Activity Scale for the Elderly (PASE) to collect information on PA during the 7-day period before stroke. PA was quantified, and patients were stratified into quartiles based on their PASE score. Cognitive performance was measured using the Symbol Digit Modalities Test (SDMT) at 1 and 6 months and the Mini-Mental State Examination (MMSE) at 6 months. The functional outcome was assessed using the modified Rankin Scale (mRS). Results In total, 625 of 642 patients (97%) completed the PASE questionnaire. The median age was 69 (interquartile range [IQR]: 60-77), and the median PASE score was 137 (82-205). Higher prestroke PASE quartiles (2nd, 3rd, and 4th, each compared to the 1st) were independently associated with a higher SDMT score at 1 month in the both the univariable and multivariable analyses (2nd: 3.99 points, 95% confidence interval [CI]: 1.01-6.97; 3rd: 3.6, CI: 0.6-6.61; 4th: 4.1, CI: 0.95-7.24). This association remained at 6 months. PA was not statistically associated with the MMSE score or mRS. Conclusion Higher prestroke PA was associated with a better cognitive performance as measured by the SDMT at 1 and 6 months poststroke. We found no significant association between prestroke PA and functional outcome. Our results are encouraging and support further investigations of PA as a protective measure against poststroke cognitive impairment.
TL;DR: IPH is associated with multiple cardiovascular risk factors, in particular advanced age, male sex, presence of carotid stenosis, and HLD, and such risk factors likely play a role in the development of IPH and may provide insight into the pathophysiology of unstableCarotid plaques.
Abstract: INTRODUCTION Intraplaque hemorrhage (IPH) is a known predictor of symptomatic cervical carotid artery disease. However, the association between IPH and modifiable cardiovascular risk factors, patient demographics, and pertinent laboratory values has not been extensively studied. METHODS A retrospective review was performed of consecutive patients who have undergone dedicated carotid plaque imaging over a 3-year period. Patients were excluded if the MR examination did not include high-resolution carotid plaque imaging. Intraplaque hyperintense signal on carotid plaque images was presumed to represent IPH. The presence or absence of IPH was compared to various demographic and clinical variables. Multivariable regression analysis was performed in order to determine an independent association between variables and IPH. RESULTS Of 643 included patients, 114 patients (17.7%) had IPH in one or both carotids, 529 patients (82.3%) did not; 39.5% of patients with IPH had coronary artery disease compared to 23.1% of patients without (p = 0.0003). Patients with IPH also had higher proportions of hypertension (77.2 vs. 60.7%, p = 0.009), hyperlipidemia (HLD; 89.5 vs. 62.4%, p < 0.0001), diabetes mellitus (29.0 vs. 18.7%, p = 0.01), and a history of tobacco smoking (63.2 vs. 52.6%, p = 0.003). Patients without IPH had, on average, higher high-density lipoprotein levels (46.1 vs. 56.7%, p = 0.003). Factors independently associated with IPH were advanced age (odds ratio [OR]: 1.1, 95% CI: [1.0-1.05], p <0.0001), male sex (OR: 2.5, 95% CI: [1.4-4.4], p = 0.0001), presence of carotid stenosis (OR: 8.4, 95% CI: [4.6-15.3], p < 0.0001), and HLD (OR: 2.6, 95% CI: [1.3-5.2], p = 0.009). CONCLUSIONS IPH is associated with multiple cardiovascular risk factors, in particular advanced age, male sex, presence of carotid stenosis, and HLD. Such risk factors likely play a role in the development of IPH and may provide insight into the pathophysiology of unstable carotid plaques.
TL;DR: Investigation of the effect of different NECT image reconstructions on the correct detection of hyperdense middle cerebral artery sign in a cohort of observers with lower experience level on NECT found MIP and thin slice reconstructions increased the sensitivity to HAS, whereas thick slab reconstructions seemed to be less appropriate.
Abstract: Introduction Cranial nonenhanced CT (NECT) imaging in hyperacute ischemic stroke is rarely used for assessing arterial obstruction of middle cerebral artery by identifying hyperdense artery sign (HAS). Considering, however, its growing importance due to its impact on the decision-making process of thrombolysis with or without mechanical thrombectomy improved sensitivity to HAS is necessary, particularly in the group of less experienced clinicians being frequently the first one assessing the presence of HAS on NECT. Objective The present study aimed to investigate the effect of different NECT image reconstructions on the correct detection of hyperdense middle cerebral artery sign in a cohort of observers with lower experience level on NECT. Particularly, MIP image reconstructions were expected to be useful for less experienced observers due to both strengthening of the hyperdensity of HAS and streamlining to less image slices. Methods Twenty-five of 100 patients' NECT image data presented with HAS. Sixteen observers with lower practice level on NECT (10 radiologists and 6 neurologists) evaluated independently the 3 image reconstructions of each data set with thin slice 1.5 mm, thick slab 5 mm, and 6-mm maximum intensity projection (MIP) and rated the presence of HAS in middle cerebral artery. A GEE model with random observer effect was used to examine the influence of the 3 image reconstructions on sensitivity to HAS. A linear mixed effects regression model was used to investigate the ranking of detectability of HAS. Interrater reliability was determined by Fleiss' kappa coefficient (κ). Results Recognition of HAS and sensitivity to HAS significantly differed between the 3 image reconstructions (p = 0.0106). MIP and thin slice reconstructions yielded each on average the highest sensitivities with 73% compared to thick slab reconstruction with 45% sensitivity. The interobserver reliability was fair (κ, 0.3-0.4). Detectability of HAS was significantly easier and better visible ranked on MIP and thin slice reconstructions compared to thick slab (p Conclusion MIP and thin slice reconstructions increased the sensitivity to HAS (73%), whereas thick slab reconstructions seemed to be less appropriate (45%).