Introduction: Acute brain infarction (BI) topology determined by diffusion weighted imaging - Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) on post-treatment magnetic resonance imaging (MRI) has been associated with clinical outcome in internal carotid artery (ICA) or proximal middle cerebral artery (MCA) occlusion treated by endovascular reperfusion therapy (EVRT). Hypothesis: We hypothesize that among the same type of patients, the topology of acute BI captured by DWI ASPECTS on baseline MRI may be associated with 3 months functional outcome after EVRT. Methods: Consecutive patients with an acute BI complicating ICA or proximal MCA occlusion treated by EVRT after a baseline MRI before treatment at a single center between April 2007 and March 2013 were enrolled. Poor functional outcome was defined by modified Rankin Scale (mRS) of 3 to 6 at 3 months. We used penalized logistic regression due to the multicollinearity between DWI-ASPECTS sites to assess the relationship between each DWI-ASPECTS sites and functional outcome after adjustment for age, sex, blood pressure, DWI lesion volume and infarct side. We estimated this relationship in the full cohort of patients and according to the achievement of a complete recanalization. Results: We enrolled 206 patients [mean age 71 ± 16.5, median NIHSS 16 (IQR 10-21)]. Among them 58 (28%) had an ICA occlusion, 115 (56%) a MCA M1 occlusion and 33 (16%) a MCA M2 occlusion. Median DWI lesion volume was 13 mL (IQR 4-43), and median DWI ASPECTS score was 6 (IQR 4-8). A complete recanalization was achieved among 96 patients (47%), after a median time from onset of 237 min (IQR:185-282). The involvement of the lentiform nucleus was associated with poor functional outcome in the full cohort of patients [OR : 10; 95% CI (5-23); p<0.0001]. This relationship was observed in the subgroup of patients who did experience a complete recanalization [OR : 4; 95% CI (1.5-12); p=0.007] and among those who did not [OR : 21; 95% CI (5-92); p<0.0001]. Conclusions: In conclusion, the involvement of the DWI ASPECTS lentiform region on baseline MRI in patients experiencing an acute BI complicating an ICA or MCA occlusion treated by EVRT was associated with poor functional outcome, overall and despite a complete recanalization.
<i>Background:</i> Ischemia-modified albumin (IMA)is a new biological marker of ischemia. Previous studies have found increased serum IMA levels after myocardial ischemia, but no study has investigated the possibility that stroke modifies IMA blood levels. <i>Materials and Methods:</i> We studied 118 consecutive patients presenting within 3 h of the onset of an acute neurological deficit [84 brain infarctions (BI), 18 brain hemorrhages (ICH) and 16 transient ischemic attacks lasting less than 1 h or epileptic seizures]. Serum samples were obtained for all patients at initial presentation and repeated only in patients with stroke at 6, 12 and 24 h. IMA was measured by the albumin-cobalt-binding test (Ischemia Technologies, Denver, Colo., USA). <i>Results:</i> The initial median IMA (bootstrap 95% confidence interval, CI) was 83 U/ml (79–86) and 86 U/ml (75–90) in patients with BI and ICH, respectively (p = 0.76), and was 73 U/ml (58–79) in others (p = 0.003 compared with BI, and p = 0.017 with ICH). Baseline IMA levels correlated with the National Institutes of Health Stroke Scale [Spearman correlation coefficient: 0.34 (p = 0.002) in BI, 0.61 (p = 0.008) in ICH]. During the first 24 h, IMA levels increased in BI patients (median, 9.1%; bootstrap 95% CI, 5.2–11.5), whereas no change was observed in ICH patients (median, 1.2%; bootstrap 95% CI, –7.8 to 6.8). <i>Conclusions:</i> IMA blood levels may be a biomarker for early identification of acute stroke. Further studies are required to investigate the role of IMA in the early detection of acute stroke.
Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain.
Objective
To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults.
Design, Setting, and Participants
This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients.
Main Outcomes and Measures
Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO).
Results
The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22).
Conclusions and Relevance
In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.
The coexistence of underlying causes in patients with transient ischemic attack (TIA) or minor ischemic stroke as well as their associated 5-year risks are not well known.
Background and Purpose- The sources of emboli in patients with embolic stroke of undetermined source (ESUS) are multiple and may not respond uniformly to anticoagulation. In this exploratory subgroup analysis of patients with carotid atherosclerosis in the NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism)-ESUS trial, we assessed whether the treatment effect in this subgroup is consistent with the overall trial population and investigated the association of carotid atherosclerosis with recurrent ischemic stroke. Methods- Carotid atherosclerosis was analyzed either as the presence of mild (ie, 20%-49%) atherosclerotic stenosis or, separately, as the presence of carotid plaque. Primary efficacy outcome was ischemic stroke recurrence. Safety outcomes were major bleeding and symptomatic intracerebral bleeding. Results- Carotid plaque was present in 40% of participants and mild carotid stenosis in 11%. There was no significant difference in ischemic stroke recurrence between rivaroxaban- and aspirin-treated patients among 490 patients with carotid stenosis (5.0 versus 5.9/100 patient-years, respectively, hazard ratio [HR], 0.85; 95% CI, 0.39-1.87; P for interaction of treatment effect with patients without carotid stenosis 0.78) and among 2905 patients with carotid plaques (5.9 versus 4.9/100 patient-years, respectively, HR, 1.20; 95% CI, 0.86-1.68; P for interaction of treatment effect with patients without carotid stenosis 0.2). Among patients with carotid plaque, major bleeding was more frequent in rivaroxaban-treated patients compared with aspirin-treated (2.0 versus 0.5/100 patient-years, HR, 3.75; 95% CI, 1.63-8.65). Patients with carotid stenosis had similar rate of ischemic stroke recurrence compared with those without (5.4 versus 4.9/100 patient-years, respectively, HR, 1.11; 95% CI, 0.73-1.69), but there was a strong trend of higher rate of ischemic stroke recurrence in patients with carotid plaque compared with those without (5.4 versus 4.3/100 patient-years, respectively, HR, 1.23; 95% CI, 0.99-1.54). Conclusions- In ESUS patients with carotid atherosclerosis, we found no difference in efficacy between rivaroxaban and aspirin for prevention of recurrent stroke, but aspirin was safer, consistent with the overall trial results. Carotid plaque was much more often present ipsilateral to the qualifying ischemic stroke than contralateral, supporting an important etiological role of nonstenotic carotid disease in ESUS. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.
The impact of prior statin use on outcomes after thrombolysis is unclear. We evaluated outcomes of patients treated by IV, intra-arterial (IA) thrombolysis, or combined therapy, according to prior statin use.We analyzed data from a patient registry (606 patients) and conducted a systematic review.We identified 11 previous studies (6,438 patients) that evaluated the effect of statin use on outcomes after IV thrombolysis (8 studies), IA thrombolysis (2 studies), or a single/combined approach (1 study). In our registry and in most of the retrieved studies, statin users had more risk factors and concomitant antiplatelet treatment than nonstatin users. Regardless of treatment strategy, prior statin use was not associated with favorable outcome (adjusted odds ratio [OR] 1.36; 95 confidence interval [CI] 0.86-2.16), symptomatic intracranial hemorrhage (sICH) (OR 0.57; 95% CI 0.22-1.49), or recanalization (OR 1.87; 95% CI 0.69-5.03). In meta-analysis, prior statin use was not associated with favorable outcome (crude OR 0.99; 95% CI 0.88-1.12), but was associated with an increased risk of sICH (crude OR 1.55; 95% CI 1.23-1.95). However, when the available multivariable associations were combined (5 studies), the effect of prior statin use on risk of sICH was not significant (OR 1.31; 95% CI 0.97-1.76).These results suggest no beneficial or detrimental effect of prior statin use in acute stroke patients treated by IV thrombolysis, IA thrombolysis, or combined therapy, although the numbers of patients treated by IA thrombolysis or combined therapy are too small to exclude an effect.
Modifications in high-density lipoprotein (HDL) particle sizes and HDL-binding proteins have been reported in stroke patients. We evaluated whether the lipoprotein profile, HDL composition and functionality were altered in stroke patients according to their clinical outcome using the modified Rankin Score at 3 months. Plasma samples were obtained from stroke patients treated with intravenous thrombolysis. Levels of cardiovascular and inflammatory markers in plasma were measured using the Human CVD Panel 1 (Milliplex® MAP). Lipoprotein subfractions from plasma were quantified by non-denaturing acrylamide gel electrophoresis, using the Lipoprint®-System (Quantimetrix®), and HDLs were isolated by ultracentrifugation. Relative amounts of paraoxonase-1 (PON1) and alpha-1 anti-trypsin (AAT) in the isolated HDLs were determined by Western blot. HDL anti-inflammatory function was evaluated in human blood-brain barrier endothelial cells stimulated with 100 ng/mL TNFα, and HDL antioxidant function was evaluated via their capacity to limit copper-induced low-density lipoprotein oxidation. Stroke patients with unfavorable outcomes had a lower proportion of small-sized HDLs and increased plasma levels of E-selectin (SELE) and the intercellular adhesion molecule 1 (ICAM1). HDLs from patients with unfavorable outcomes had lower levels of PON1 and displayed a blunted capacity to reduce the expression of SELE, interleukin 8 (IL8) and the monocyte chemoattractant protein-1 (MCP1) mRNA induced by TNFα in endothelial cells. These HDLs also had a reduced antioxidant capacity relative to HDLs from healthy donors. In conclusion, an increased ratio of large/small HDLs with impaired anti-inflammatory and antioxidant capacities was associated with unfavorable outcomes in stroke patients. Alteration of HDL functionality was mainly associated with a low amount of PON1 and high amount of AAT.
Background and Purpose— Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization. Methods— We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days. Results— A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5–43) after a median onset time to imaging of 110 minutes (interquartile range, 77–178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31–0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206–285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90–13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles ( P <0.005). Conclusions— Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.
As a result of contraindications (eg, frailty, cognitive impairment, comorbidities) or patient refusal, many patients with stroke and atrial fibrillation cannot be discharged on oral anticoagulant. Among them, the proportion of potential candidates for left atrial appendage closure (LAAC) and their 12-month outcome is not well known.The prospective WATCH-AF registry (Warfarin Aspirin Ten-A Inhibitors and Cerebral Infarction and Hemorrhage and Atrial Fibrillation) enrolled consecutive patients admitted within 72 hours of an acute stroke associated with atrial fibrillation in 2 stroke centers. Scales to evaluate stroke severity, disability, functional independence, risk of fall, cognition, ischemic and hemorrhagic risk-stratification, and comorbidities were systematically collected at admission, discharge, 3, 12 months poststroke. The 2 main end points were death or dependency (modified Rankin Scale score >3) and recurrent stroke (brain infarction and brain hemorrhage).Among 400 enrolled patients (370 with brain infarction, 30 with brain hemorrhage), 31 died before discharge and 57 (14.3%) were possible European Heart Rhythm Association/European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Rhythm Society candidates for LAAC. At 12 months, the rate of death or dependency was 17.9%, and the rate of stroke recurrence was 9.8% in the 274/400 (68.5%) patients discharged on a long-term oral anticoagulant strategy, as compared with 17.5% and 24.7%, respectively, in 57 patients candidate for LAAC. As compared with patients on a long-term oral anticoagulant strategy, there was a 2-fold increase in the risk of stroke recurrence in the group with an indication for LAAC (adjusted hazard ratio, 2.58 [95% CI, 1.40-4.76]; P=0.002).Fourteen percent of patients with stroke associated with atrial fibrillation were potential candidates for LAAC. The 12-month stroke risk of these candidates was 3-fold the risk of anticoagulated patients.
Background and Purpose— Dramatic recovery (DR) is a predictor of stroke outcome among others. However, after successful recanalization, systematic favorable outcome is not the rule. We sought to analyze the impact of recanalization on DR in patients with acute ischemic stroke eligible for any revascularization strategies (either intravenous or endovascular). Methods— We analyzed data collected between April 2007 and May 2011 in our prospective clinical registry. All patients with acute ischemic stroke with National Institutes of Health Stroke Scale ≥10 at admission and an identification of arterial status before treatment were included. DR was defined as National Institutes of Health Stroke Scale ≤3 at 24 hours or a decrease of ≥10 points within 24 hours. Results— DR occurred in 75 of 255 patients with acute ischemic stroke (29.4%). Patients with persistent occlusion had a low DR rate (11.1%) than those with no documented occlusion (36.5%) and those with occlusion followed by recanalization (35.3%; both P <0.001). Among patients with recanalization monitored by angiography, DR was higher among patients with complete recanalization than among those with partial recanalization (46.8% versus 14.3%; P <0.001) and increased with tertiles of time to recanalization ( P trend =0.002). In multivariable logistic regression analysis, grade and time to recanalization appeared independently associated with DR; the adjusted ORs were 4.17 (95% CI, 1.61–10.77) for complete recanalization and 1.24 (95% CI, 1.04–1.48) for each 30-minute time decrease. Patients with versus without DR more frequently had modified Rankin Scale ≤1 (67.6% versus 9.0%; P <0.001) and less frequently had hemorrhage (17.3% versus 33.9%; P =0.024). Conclusions— DR is strongly associated with favorable clinical outcome and is dependent on complete recanalization and time to recanalization.
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