Efficacy of interactive manual dexterity training after stroke: a pilot single-blinded randomized controlled trial.

OBJECTIVE: To compare the efficacy of Dextrain Manipulandum™ training of dexterity components such as force control and independent finger movements, to dose-matched conventional therapy (CT) post-stroke. METHODS: A prospective, single-blind, pilot randomized clinical trial was conducted. Chronic-phase post-stroke patients with mild-to-moderate dexterity impairment (Box and Block Test (BBT) > 1) received 12 sessions of Dextrain or CT. Blinded measures were obtained before and after training and at 3-months follow-up. Primary outcome was BBT-change (after-before training). Secondary outcomes included changes in motor impairments, activity limitations and dexterity components. Corticospinal excitability and short intracortical inhibition (SICI) were measured using transcranial magnetic stimulation. RESULTS: BBT-change after training did not differ between the Dextrain (N = 21) vs CT group (N = 21) (median [IQR] = 5[2-7] vs 4[2-7], respectively; P = 0.36). Gains in BBT were maintained at the 3-month post-training follow-up, with a non-significant trend for enhanced BBT-change in the Dextrain group (median [IQR] = 3[- 1-7.0], P = 0.06). Several secondary outcomes showed significantly larger changes in the Dextrain group: finger tracking precision (mean ± SD = 0.3 ± 0.3N vs - 0.1 ± 0.33N; P < 0.0018), independent finger movements (34.7 ± 25.1 ms vs 7.7 ± 18.5 ms, P = 0.02) and maximal finger tapping speed (8.4 ± 7.1 vs 4.5 ± 4.9, P = 0.045). At follow-up, Dextrain group showed significantly greater improvement in Motor Activity Log (median/IQR = 0.7/0.2-0.8 vs 0.2/0.1-0.6, P = 0.05). Across both groups SICI increased in patients with greater BBT-change (Rho = 0.80, P = 0.006). Comparing Dextrain subgroups with maximal grip force higher/lower than median (61.2%), BBT-change was significantly larger in patients with low vs high grip force (7.5 ± 5.6 vs 2.9 ± 2.8; respectively, P = 0.015). CONCLUSIONS: Although immediate improvements in gross dexterity post-stroke did not significantly differ between Dextrain training and CT, our findings suggest that Dextrain enhances recovery of several dexterity components and reported hand-use, particularly when motor impairment is moderate (low initial grip force). Findings need to be confirmed in a larger trial. Trial registration ClinicalTrials.gov NCT03934073 (retrospectively registered).

Cathodal Transcranial Direct Current Stimulation in Acute Ischemic Stroke: Pilot Randomized Controlled Trial.

Background and Purpose: In acute stroke, preventing infarct growth until complete recanalization occurs is a promising approach as an adjunct to reperfusion therapies to reduce infarct size and improve outcome. In rodent models, cathodal transcranial direct current stimulation (C-tDCS) decreases peri-infarct depolarizations and reduces infarct volume. We hypothesized that C-tDCS would nonpharmacologically reduce infarct growth in hyperacute middle cerebral artery territory stroke patients receiving reperfusion therapy. Methods: STICA (Cathodal Transcranial Direct Stimulation in Acute Middle Cerebral Artery Stroke) was a pilot single-center, double-blind, 2-arms 1:1 randomized trial evaluating the safety, feasibility, and efficacy of C-tDCS versus sham stimulation in patients eligible for recanalization therapies. Magnetic resonance imaging was obtained both on admission and 24 hours later. The primary end point was 24-hour infarct growth. Secondary outcomes were (1) National Institutes of Health Stroke Scale score difference between day 7 and admission and (2) 3-month modified Rankin Scale score. Results: Forty-five patients were randomized. Median magnetic resonance imaging-to-C-tDCS start time was 45 minutes; C-tDCS was started before completion of recanalization procedure in all patients. The intervention proved feasible in all patients. No major adverse effects occurred in either group. There was no significant difference between active and sham groups for any end point. However, an apparent trend towards smaller infarct growth in the C-tDCS arm was observed in the whole group (unadjusted median difference [IC95%]: −2.2 mL [−12.2 to 1.5]) and in the prespecified subsamples with moderate-to-severe stroke and large vessel occlusion (−5.7 mL [−21.6 to 2.6] and −7.7 mL [−24.2 to 2.6], respectively). Conclusions: C-tDCS was feasible and well tolerated. No significant difference was found between the active and sham groups. However, the data suggest potential benefits of C-tDCS in patients with National Institutes of Health Stroke Scale score of >10 or large vessel occlusion. Using the observed effect size and standard α=5% and ß=20%, samples of 102 and 86, respectively, can be estimated for future trials in patients with these characteristics. Randomized trials particularly targeting these populations may be warranted.

Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials.

BACKGROUND AND PURPOSE: CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) reported a higher periprocedural risk for any stroke, death, or myocardial infarction for women randomized to carotid artery stenting (CAS) compared with women randomized to carotid endarterectomy (CEA). No difference in risk by treatment was detected for women relative to men in the 4-year primary outcome. We aimed to conduct a pooled analysis among symptomatic patients in large randomized trials to provide more precise estimates of sex differences in the CAS-to-CEA risk for any stroke or death during the 120-day periprocedural period and ipsilateral stroke thereafter. METHODS: Data from the Carotid Stenosis Trialists' Collaboration included outcomes from symptomatic patients in EVA-3S (Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis), SPACE (Stent-Protected Angioplasty Versus Carotid Endarterectomy in Symptomatic Patients), ICSS (International Carotid Stenting Study), and CREST. The primary outcome was any stroke or death within 120 days after randomization and ipsilateral stroke thereafter. Event rates and relative risks were estimated using Poisson regression; effect modification by sex was assessed with a sex-by-treatment-by-trial interaction term, with significant interaction defined a priori as P≤0.10. RESULTS: Over a median 2.7 years of follow-up, 433 outcomes occurred in 3317 men and 1437 women. The CAS-to-CEA relative risk of the primary outcome was significantly lower for women compared with men in 1 trial, nominally lower in another, and nominally higher in the other two. The sex-by-treatment-by-trial interaction term was significant (P=0.065), indicating heterogeneity among trials. Contributors to this heterogeneity are primarily differences in periprocedural period. When the trials are nevertheless pooled, there were no significant sex differences in risk in any follow-up period. CONCLUSIONS: There were significant differences between trials in the magnitude of sex differences in treatment effect (CAS-to-CEA relative risk), indicating pooling data from these trials to estimate sex differences might not be valid. Whether sex is acting as an effect modifier of the CAS-to-CEA treatment effect in symptomatic patients remains uncertain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00190398 (EVA-3S) and NCT00004732 (CREST). URL: https://www.isrctn.com; Unique identifier: ISRCTN57874028 (SPACE) and ISRCTN25337470 (ICSS).

Genome wide association study of silent cerebral infarction in sickle cell disease (HbSS and HbSC).

Not available.

Transcranial color-coded duplex sonography reliably identifies intracranial vasculopathy in adult patients with sickle cell disease.

In order to prevent stroke, screening for disease-related intracranial vasculopathy using Doppler ultrasound is recommended in sickle-cell disease (SCD) children. How to screen such vasculopathy in adults remains largely unknown. The objective of this study was to assess whether transcranial color-coded duplex sonography (TCCD) is sensitive and specific enough to identify SCD adult patients with vasculopathy, compared with magnetic resonance angiography (MRA). Sickle cell disease adults followed in referral centers at high risk of vasculopathy were included in this study. Transcranial color-coded duplex sonography examination and 3-D time-of-flight MRA were performed on the same day. On MRA, vasculopathy was defined by the presence of at least one ≥50% arterial stenosis. On TCCD, vasculopathy was defined by a time-averaged mean of the maximum velocity (TAMx) stenotic/prestenotic ratio ≥ 3, an occlusion, or a Moyamoya pattern. Vasculopathy was also considered as present when TAMx ratio could not be calculated because of the presence of severe cervical lesions. Among 80 included patients, quality of MRA was insufficient in three patients. Among the 38 patients with vasculopathy on MRA, 37 had a vasculopathy according to TCCD criteria: TAMx ratio ≥ 3 or intracranial occlusion in 33 patients and cervical lesion in four patients. A Moyamoya pattern was identified with TCCD in all 17 patients with Moyamoya on MRA. Sensitivity and specificity of TCCD to identify patients with ≥50% vasculopathy on MRA were (n = 37/38) 97% and (n = 28/34) 82%, respectively. Positive and negative predictive values were (n = 37/43) 86% and (n = 28/29) 97%, respectively. Note, TCCD may be used to identify SCD adult patients with vasculopathy.

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

A meta-analysis of poststroke depression risk factors comparing depressive-related factors versus others.

OBJECTIVES: Poststroke depression (PSD) is a public health issue, affecting one-third of stroke survivors, and is associated with multiple negative consequences. Reviews tried to identify PSD risk factors with discrepant results, highlighting the lack of comparability of the analyzed studies. We carried out a meta-analysis in order to identify clinical risk factors that can predict PSD. DESIGN: PubMed and Web of Science were searched for papers. Only papers with a strictly defined Diagnostic and Statistical Manual of Mental Disorders depression assessment, at least 2 weeks after stroke, were selected. Two authors independently evaluated potentially eligible studies that were identified by our search and independently extracted data using standardized spreadsheets. Analyses were performed using MetaWin®, the role of each variable being given as a risk ratio (RR). RESULTS: Eighteen studies were included in the meta-analysis. Identified risk factors for PSD with RR significantly above 1 were previous history of depression (RR 2.19, confidence interval (CI) 1.52-3.15), disability (RR 2.00, CI 1.58-2.52), previous history of stroke (RR 1.68, CI 1.06-2.66), aphasia (RR 1.47, CI 1.13-1.91), and female gender (RR 1.35, CI 1.14-1.61). Fixed effects model leads to identification of two more risk factors: early depressive symptoms with an RR of 2.32 (CI 1.43-3.79) and tobacco consumption (RR 1.40, CI 1.09-1.81). Time bias was found for alcohol consumption. Sample size was significantly involved to explain the role of "alcohol consumption" and "cognitive impairment." CONCLUSION: Five items were significantly predictive of PSD. It might be of clinical interest that depressive-related risk factors (such as past depressive episodes) were having the largest impact.

Impact of panelists' experience on script concordance test scores of medical students.

BACKGROUND: The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. METHODS: In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. RESULTS: A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students' SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p < 0.0001 if N = 20; 67.2 vs 70.1, p < 0.0001 if N = 15 and 67.7 vs 68.4, p < 0.0001 if N = 10) and with EP compared to NEP (65.4 vs 67.1, p < 0.0001 if N = 20; 66.0 vs 67.2, p < 0.0001 if N = 15 and 62.5 vs 67.7, p < 0.0001 if N = 10). Bland & Altman plots showed good concordances between students' SCT scores, whatever the experience level of the expert panel. CONCLUSIONS: Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.

Associations of Perioperative Variables With the 30-Day Risk of Stroke or Death in Carotid Endarterectomy for Symptomatic Carotid Stenosis.

Background and Purpose- This analysis was performed to assess the association between perioperative and clinical variables and the 30-day risk of stroke or death after carotid endarterectomy for symptomatic carotid stenosis. Methods- Individual patient-level data from the 5 largest randomized controlled carotid trials were pooled in the Carotid Stenosis Trialists' Collaboration database. A total of 4181 patients who received carotid endarterectomy for symptomatic stenosis per protocol were included. Determinants of outcome included carotid endarterectomy technique, type of anesthesia, intraoperative neurophysiological monitoring, shunting, antiplatelet medication, and clinical variables. Stroke or death within 30 days after carotid endarterectomy was the primary outcome. Adjusted risk ratios (aRRs) were estimated in multilevel multivariable analyses using a Poisson regression model. Results- Mean age was 69.5±9.2 years (70.7% men). The 30-day stroke or death rate was 4.3%. In the multivariable regression analysis, local anesthesia was associated with a lower primary outcome rate (versus general anesthesia; aRR, 0.70 [95% CI, 0.50-0.99]). Shunting (aRR, 1.43 [95% CI, 1.05-1.95]), a contralateral high-grade carotid stenosis or occlusion (aRR, 1.58 [95% CI, 1.02-2.47]), and a more severe neurological deficit (mRS, 3-5 versus 0-2: aRR, 2.51 [95% CI, 1.30-4.83]) were associated with higher primary outcome rates. None of the other characteristics were significantly associated with the perioperative stroke or death risk. Conclusions- The current results indicate lower perioperative stroke or death rates in patients operated upon under local anesthesia, whereas a more severe neurological deficit and a contralateral high-grade carotid stenosis or occlusion were identified as potential risk factors. Despite a possible selection bias and patients not having been randomized, these findings might be useful to guide surgeons and anesthetists when treating patients with symptomatic carotid disease.

Safety of Carotid Revascularization in Patients With a History of Coronary Heart Disease.

Background and Purpose- We investigated whether procedural stroke or death risk of carotid artery stenting (CAS) compared with carotid endarterectomy (CEA) is different in patients with and without history of coronary heart disease (CHD) and whether the treatment-specific impact of age differs. Methods- We combined individual patient data of 4754 patients with symptomatic carotid stenosis from 4 randomized trials (EVA-3S [Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis], SPACE [Stent-Protected Angioplasty Versus Carotid Endarterectomy], ICSS [International Carotid Stenting Study], and CREST [Carotid Revascularization Endarterectomy Versus Stenting Trial]). Procedural risk was defined as any stroke or death ≤30 days after treatment. We compared procedural risk between both treatments with Cox regression analysis, stratified by history of CHD and age (<70, 70-74, ≥75 years). History of CHD included myocardial infarction, angina, or coronary revascularization. Results- One thousand two hundred ninety-three (28%) patients had history of CHD. Procedural stroke or death risk was higher in patients with history of CHD. Procedural risk in patients treated with CAS compared with CEA was consistent in patients with history of CHD (8.3% versus 4.6%; hazard ratio [HR], 1.96; 95% CI, 0.67-5.73) and in those without (6.9% versus 3.6%; HR, 1.93; 95% CI, 1.40-2.65; Pinteraction=0.89). In patients with history of CHD, procedural risk was significantly higher after CAS compared with CEA in patients aged ≥75 (CAS-to-CEA HR, 2.78; 95% CI, 1.32-5.85), but not in patients aged <70 (HR, 1.71; 95% CI, 0.79-3.71) and 70 to 74 years (HR, 1.09; 95% CI, 0.45-2.65). In contrast, in patients without history of CHD, procedural risk after CAS was higher in patients aged 70 to 74 (HR, 3.62; 95% CI, 1.80-7.29) and ≥75 years (HR, 2.64; 95% CI, 1.52-4.59), but equal in patients aged <70 years (HR, 1.05; 95% CI, 0.63-1.73; 3-way Pinteraction=0.09). Conclusions- History of CHD does not modify procedural stroke or death risk of CAS compared with CEA. CAS might be as safe as CEA in patients with history of CHD aged <75 years, whereas for patients without history of CHD, risk after CAS compared with CEA was only equal in those aged <70 years.

Carotid Plaque Inflammation Imaged by 18F-Fluorodeoxyglucose Positron Emission Tomography and Risk of Early Recurrent Stroke.

Background and Purpose- Plaque inflammation contributes to stroke and coronary events. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identifies plaque inflammation-related metabolism. Almost no prospective data exist on the relationship of carotid 18F-FDG uptake and early recurrent stroke. Methods- We did a multicenter prospective cohort study BIOVASC (Biomarkers/Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease) of patients with carotid stenosis and recent stroke/transient ischemic attack with 90-day follow-up. On coregistered carotid 18F-FDG PET/computed tomography angiography, 18F-FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest slice. We then conducted a systematic review of similar studies and pooled unpublished individual-patient data with 2 highly similar independent studies (Dublin and Barcelona). We analyzed the association of SUVmax with all recurrent nonprocedural stroke (before and after PET) and with recurrent stroke after PET only. Results- In BIOVASC (n=109, 14 recurrent strokes), after adjustment (for age, sex, stenosis severity, antiplatelets, statins, diabetes mellitus, hypertension, and smoking), the hazard ratio for recurrent stroke per 1 g/mL SUVmax was 2.2 (CI, 1.1-4.5; P=0.025). Findings were consistent in the independent Dublin (n=52, hazard ratio, 2.2; CI, 1.1-4.3) and Barcelona studies (n=35, hazard ratio, 2.8; CI, 0.98-5.5). In the pooled cohort (n=196), 37 recurrent strokes occurred (29 before and 8 after PET). Plaque SUVmax was higher in patients with all recurrence ( P<0.0001) and post-PET recurrence ( P=0.009). The fully adjusted hazard ratio of any recurrent stroke was 2.19 (CI, 1.41-3.39; P<0.001) and for post-PET recurrent stroke was 4.57 (CI, 1.5-13.96; P=0.008). Recurrent stroke risk increased across SUVmax quartiles (log-rank P=0.003). The area under receiver operating curve for all recurrence was 0.70 (CI, 0.59-0.78) and for post-PET recurrence was 0.80 (CI, 0.64-0.96). Conclusions- Plaque inflammation-related 18F-FDG uptake independently predicted future recurrent stroke post-PET. Although further studies are needed, 18F-FDG PET may improve patient selection for carotid revascularization and suggest that anti-inflammatory agents may have benefit for poststroke vascular prevention.

Optimal 4DFlow MR sequence parameters for the assessment of internal carotid artery stenosis: a simulation study.

PURPOSE: In patients with ICA stenosis, increased peak systolic velocity is a marker of stenosis at risk of ischemic stroke. 4DFlow MRI is a reproducible technique to evaluate velocities in ICA stenosis, although it seems to underestimate velocities as compared with Doppler ultrasonography. The purpose of our study was to confirm that velocities were underestimated on a new set of data acquired with a clinical 4DFlow sequence, and to devise optimal acquisition parameters for ICA stenosis exploration based on a numerical simulation. METHODS: After review board approval, 15 healthy controls and 12 patients presenting ICA stenosis were explored with Doppler ultrasonography and 4DFlow MRI. We created a 2-dimensional simulation of ICA stenosis and its corresponding 4DFlow acquisition, and compared its mean peak systolic velocity underestimation to real MRI and Doppler. We then simulated the acquisition for voxel size ranging from 0.5 to 1.25 mm and number of phases per cardiac cycle ranging from 10 to 25. RESULTS: On acquired data, 4DFlow MR underestimated peak systolic velocities (mean difference between Doppler and 4DFlow: - 35 cm/s), especially high velocities. With spatial and temporal resolutions equivalent to MR acquisition, our simulation yielded similar underestimation (mean difference: - 31 cm/s, P = 0.30). Simulations showed that 0.7-mm resolution and 20 phases per cardiac cycle would be necessary to record peak systolic velocities up to 250 cm/s. CONCLUSION: Higher spatial resolution can provide accurate peak systolic velocities measurement with 4DFlow MRI, thus allowing better ICA stenosis assessment. Further studies are needed to validate the proposed parameters.

Immediate and Delayed Procedural Stroke or Death in Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis.

Background and Purpose- Stenting for symptomatic carotid stenosis (carotid artery stenting [CAS]) carries a higher risk of procedural stroke or death than carotid endarterectomy (CEA). It is unclear whether this extra risk is present both on the day of procedure and within 1 to 30 days thereafter and whether clinical risk factors differ between these periods. Methods- We analyzed the risk of stroke or death occurring on the day of procedure (immediate procedural events) and within 1 to 30 days thereafter (delayed procedural events) in 4597 individual patients with symptomatic carotid stenosis who underwent CAS (n=2326) or CEA (n=2271) in 4 randomized trials. Results- Compared with CEA, patients treated with CAS were at greater risk for immediate procedural events (110 versus 42; 4.7% versus 1.9%; odds ratio, 2.6; 95% CI, 1.9-3.8) but not for delayed procedural events (59 versus 46; 2.5% versus 2.0%; odds ratio, 1.3; 95% CI, 0.9-1.9; interaction P=0.006). In patients treated with CAS, age increased the risk for both immediate and delayed events while qualifying event severity only increased the risk of delayed events. In patients treated with CEA, we found no risk factors for immediate events while a higher level of disability at baseline and known history of hypertension were associated with delayed procedural events. Conclusions- The increased procedural stroke or death risk associated with CAS compared with CEA was caused by an excess of events occurring on the day of procedure. This finding demonstrates the need to enhance the procedural safety of CAS by technical improvements of the procedure and increased operator skill. Higher age increased the risk for both immediate and delayed procedural events in CAS, mechanisms of which remain to be elucidated. Clinical Trial Registration- URL: https://clinicaltrials.gov . Unique identifier: NCT00190398. URL: http://www.isrctn.com . Unique identifier: ISRCTN57874028. URL: http://www.isrctn.com . Unique identifier: ISRCTN25337470. URL: https://clinicaltrials.gov . Unique identifier: NCT00004732.

Prediction Models for Clinical Outcome After a Carotid Revascularization Procedure.

Background and Purpose- Prediction models may help physicians to stratify patients with high and low risk for periprocedural complications or long-term stroke risk after carotid artery stenting or carotid endarterectomy. We aimed to evaluate external performance of previously published prediction models for short- and long-term outcome after carotid revascularization in patients with symptomatic carotid artery stenosis. Methods- From a literature review, we selected all prediction models that used only readily available patient characteristics known before procedure initiation. Follow-up data from 2184 carotid artery stenting and 2261 carotid endarterectomy patients from 4 randomized trials (EVA-3S [Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis], SPACE [Stent-Protected Angioplasty Versus Carotid Endarterectomy], ICSS [International Carotid Stenting Study], and CREST [Carotid Revascularization Endarterectomy Versus Stenting Trial]) were used to validate 23 short-term outcome models to estimate stroke or death risk ≤30 days after the procedure and the original outcome measure for which the model was developed. Additionally, we validated 7 long-term outcome models for the original outcome measure. Predictive performance of the models was assessed with C statistics and calibration plots. Results- Stroke or death ≤30 days after the procedure occurred in 158 (7.2%) patients after carotid artery stenting and in 84 (3.7%) patients after carotid endarterectomy. Most models for short-term outcome after carotid artery stenting (n=4) or carotid endarterectomy (n=19) had poor discriminative performance (C statistics ranging from 0.49-0.64) and poor calibration with small absolute risk differences between the lowest and highest risk groups and overestimation of risk in the highest risk groups. Long-term outcome models (n=7) had a slightly better performance with C statistics ranging from 0.59 to 0.67 and reasonable calibration. Conclusions- Current models did not reliably predict outcome after carotid revascularization in a trial population of patients with symptomatic carotid stenosis. In particular, prediction of short-term outcome seemed to be difficult. Further external validation of existing prediction models or development of new prediction models is needed before such models can be used to support treatment decisions in individual patients.

Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4 Randomized Controlled Trials.

BACKGROUND AND PURPOSE: Patients undergoing carotid endarterectomy (CEA) for symptomatic stenosis of the internal carotid artery benefit from early intervention. Heterogeneous data are available on the influence of timing of carotid artery stenting (CAS) on procedural risk. METHODS: We investigated the association between timing of treatment (0-7 days and >7 days after the qualifying neurological event) and the 30-day risk of stroke or death after CAS or CEA in a pooled analysis of individual patient data from 4 randomized trials by the Carotid Stenosis Trialists' Collaboration. Analyses were done per protocol. To obtain combined estimates, logistic mixed models were applied. RESULTS: Among a total of 4138 patients, a minority received their allocated treatment within 7 days after symptom onset (14% CAS versus 11% CEA). Among patients treated within 1 week of symptoms, those treated by CAS had a higher risk of stroke or death compared with those treated with CEA: 8.3% versus 1.3%, risk ratio, 6.7; 95% confidence interval, 2.1 to 21.9 (adjusted for age at treatment, sex, and type of qualifying event). For interventions after 1 week, CAS was also more hazardous than CEA: 7.1% versus 3.6%, adjusted risk ratio, 2.0; 95% confidence interval, 1.5 to 2.7 (P value for interaction with time interval 0.06). CONCLUSIONS: In randomized trials comparing stenting with CEA for symptomatic carotid artery stenosis, CAS was associated with a substantially higher periprocedural risk during the first 7 days after the onset of symptoms. Early surgery is safer than stenting for preventing future stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00190398; URL: http://www.controlled-trials.com. Unique identifier: ISRCTN57874028; Unique identifier: ISRCTN25337470; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Symptomatic carotid stenosis: is stenting as safe and effective as carotid endarterectomy?

PURPOSE OF REVIEW: Reviewing current evidence on carotid artery stenting (CAS) compared with carotid endarterectomy (CEA) in the prevention of ipsilateral stroke in patients with a symptomatic carotid stenosis. RECENT FINDINGS: Randomized clinical trials and registries have consistently shown that CAS is associated with a higher risk of procedural stroke or death and a lower risk of procedural myocardial infarction and local complications compared with CEA. Both procedures are equally effective to prevent late recurrent ipsilateral stroke and are associated with similar low risk of restenosis.Individual patient data analyses of the Carotid Stenosis Trialists' Collaboration recently showed that CAS is as safe and as effective in patients younger than 70. SUMMARY: Although CEA remains the standard treatment in patients with recently symptomatic carotid stenosis, CAS is a safe and effective alternative option in patients younger than 70 and can be also considered when a contraindication to CEA exists.

Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials.

BACKGROUND: Age was reported to be an effect-modifier in four randomised controlled trials comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA), with better CEA outcomes than CAS outcomes noted in the more elderly patients. We aimed to describe the association of age with treatment differences in symptomatic patients and provide age-specific estimates of the risk of stroke and death within narrow (5 year) age groups. METHODS: In this meta-analysis, we analysed individual patient-level data from four randomised controlled trials within the Carotid Stenosis Trialists' Collaboration (CSTC) involving patients with symptomatic carotid stenosis. We included only trials that randomly assigned patients to CAS or CEA and only patients with symptomatic stenosis. We assessed rates of stroke or death in 5-year age groups in the periprocedural period (between randomisation and 120 days) and ipsilateral stroke during long-term follow-up for patients assigned to CAS or CEA. We also assessed differences between CAS and CEA. All analyses were done on an intention-to-treat basis. FINDINGS: Collectively, 4754 patients were randomly assigned to either CEA or CAS treatment in the four studies. 433 events occurred over a median follow-up of 2·7 years. For patients assigned to CAS, the periprocedural hazard ratio (HR) for stroke and death in patients aged 65-69 years compared with patients younger than 60 years was 2·16 (95% CI 1·13-4·13), with HRs of roughly 4·0 for patients aged 70 years or older. We noted no evidence of an increased periprocedural risk by age group in the CEA group (p=0·34). These changes underpinned a CAS-versus CEA periprocedural HR of 1·61 (95% CI 0·90-2·88) for patients aged 65-69 years and an HR of 2·09 (1·32-3·32) for patients aged 70-74 years. Age was not associated with the postprocedural stroke risk either within treatment group (p≥0·09 for CAS and 0·83 for CEA), or between treatment groups (p=0·84). INTERPRETATION: In these RCTs, CEA was clearly superior to CAS in patients aged 70-74 years and older. The difference in older patients was almost wholly attributable to increasing periprocedural stroke risk in patients treated with CAS. Age had little effect on CEA periprocedural risk or on postprocedural risk after either procedure. FUNDING: None.

Fluid-Attenuated Inversion Recovery Vascular Hyperintensities-Diffusion-Weighted Imaging Mismatch Identifies Acute Stroke Patients Most Likely to Benefit From Recanalization.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery vascular hyperintensities (FVH) beyond the boundaries of diffusion-weighted imaging (DWI) lesion (FVH-DWI mismatch) have been proposed as an alternative to perfusion-weighted imaging (PWI)-DWI mismatch. We aimed to establish whether FVH-DWI mismatch can identify patients most likely to benefit from recanalization. METHODS: FVH-DWI mismatch was assessed in 164 patients with proximal middle cerebral artery occlusion before intravenous thrombolysis. PWI-DWI mismatch (PWITmax>6sec/DWI>1.8) was assessed in the 104 patients with available PWI data. We tested the associations between 24-hours complete recanalization on magnetic resonance angiography and 3-month favorable outcome (modified Rankin Scale score ≤2), stratified on FVH-DWI (or PWI-DWI) status. RESULTS: FVH-DWI mismatch was present in 121/164 (74%) patients and recanalization in 50/164 (30%) patients. The odds ratio for favorable outcome with recanalization was 16.2 (95% confidence interval, 5.7-46.5; P<0.0001) in patients with FVH-DWI mismatch and 2.6 (95% confidence interval, 0.6-12.1; P=0.22) in those without FVH-DWI mismatch (P=0.048 for interaction). Recanalization was associated with favorable outcome in patients with PWI-DWI mismatch (odds ratios, 9.9; 95% confidence interval, 3.1-31.3; P=0.0001) and in patients without PWI-DWI mismatch (odds ratios, 7.0; 95% confidence interval, 1.1-44.1; P=0.047), P=0.76 for interaction. CONCLUSION: The FVH-DWI mismatch may rapidly identify patients with proximal occlusion most likely to benefit from recanalization.

Clinical Scales Do Not Reliably Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion.

BACKGROUND AND PURPOSE: It remains debated whether clinical scores can help identify acute ischemic stroke patients with large-artery occlusion and hence improve triage in the era of thrombectomy. We aimed to determine the accuracy of published clinical scores to predict large-artery occlusion. METHODS: We assessed the performance of 13 clinical scores to predict large-artery occlusion in consecutive patients with acute ischemic stroke undergoing clinical examination and magnetic resonance or computed tomographic angiography ≤6 hours of symptom onset. When no cutoff was published, we used the cutoff maximizing the sum of sensitivity and specificity in our cohort. We also determined, for each score, the cutoff associated with a false-negative rate ≤10%. RESULTS: Of 1004 patients (median National Institute of Health Stroke Scale score, 7; range, 0-40), 328 (32.7%) had an occlusion of the internal carotid artery, M1 segment of the middle cerebral artery, or basilar artery. The highest accuracy (79%; 95% confidence interval, 77-82) was observed for National Institute of Health Stroke Scale score ≥11 and Rapid Arterial Occlusion Evaluation Scale score ≥5. However, these cutoffs were associated with false-negative rates >25%. Cutoffs associated with an false-negative rate ≤10% were 5, 1, and 0 for National Institute of Health Stroke Scale, Rapid Arterial Occlusion Evaluation Scale, and Cincinnati Prehospital Stroke Severity Scale, respectively. CONCLUSIONS: Using published cutoffs for triage would result in a loss of opportunity for ≥20% of patients with large-artery occlusion who would be inappropriately sent to a center lacking neurointerventional facilities. Conversely, using cutoffs reducing the false-negative rate to 10% would result in sending almost every patient to a comprehensive stroke center. Our findings, therefore, suggest that intracranial arterial imaging should be performed in all patients with acute ischemic stroke presenting within 6 hours of symptom onset.

First Ischemic Stroke in Sickle-Cell Disease: Are There Any Adult Specificities?

BACKGROUND AND PURPOSE: There is little evidence about characteristics of ischemic stroke (IS) occurring in adults with sickle-cell disease (SCD). The objective of this study was to assess characteristics of first-ever IS in adults with SCD and to assess whether they differ from those occurring in child patients with SCD. METHODS: Adult and child individuals with SCD who had a first-ever IS were identified from cohorts of patients followed up in an adult and a child sickle cell referral center. Mechanisms of IS were determined by consensus meeting from all available explorations using the following predefined classification: Vasculopathy, cardioembolism, other defined cause, and undetermined. Treatment and stroke recurrences were recorded from prospective follow-up performed in the referral centers. RESULTS: Twenty-nine adults and 26 children had a first-ever IS; mean age (SD) was 7.1 (4.3) and 32.3 (11.6), respectively. With regard to IS mechanism, vasculopathy was less often the cause of IS in adults (12/29, 41%) than in children (24/26, 92%; P<0.001). Other causes of IS in adults were cardioembolism in 7, antiphospholipid syndrome in 1, toxic (cocaine) in 1, and undetermined in 8. Adults with SCD had a higher risk of recurrent stroke (23.1% [7.0-39.2] at 5 years) compared with children (1 recurrence only; P log rank=0.046) despite exchange-blood transfusion in patients with vasculopathy. CONCLUSIONS: First-ever IS occurring in adults with SCD has specificities that justify further studies conducted in adults with SCD to improve understanding and management.