Undiagnosed major risk factors in acute ischaemic stroke patients: frequency, profile, stroke mechanisms and outcome.

BACKGROUND AND PURPOSE: There is scarce clinical information about the clinical profile of patients with acute ischaemic stroke with previously undiagnosed major vascular risk factors (UMRFs). METHODS: This was a retrospective analysis of data from the Acute Stroke Registry and Analysis of Lausanne registry between 2003 and 2018 with univariate and multivariate logistic regression analyses comparing clinical profiles of patients with UMRFs to patients with at least one previously diagnosed MRF (DMRF). RESULTS: In all, 4354 patients (median age 70 years [interquartile range 15.2], 44.7% female) were included after excluding 763 (14.9%) for lack of consent and three for missing information. Amongst 1125 (25.8%) UMRF patients, 69.7% (n = 784) had at least one newly diagnosed MRF and the others none. The newly detected MRFs were dyslipidaemia (61.4%), hypertension (23.7%), atrial fibrillation (10.2%), diabetes mellitus (5.2%), ejection fraction <35% (2.0%) and coronary disease (1.0%). Comparing UMRF patients to DMRF patients, multivariate analysis showed a positive association with lower age, non-Caucasian ethnicity, contraceptive use (<55 years old), smoking (≥55 years old) and patent-foramen-ovale-related stroke mechanism. A negative association was found with pre-stroke antiplatelet use and higher body mass index. Functional outcome did not differ. Cerebrovascular recurrences were similar between groups. CONCLUSIONS: In this large single-centre cohort, 69.7% of patients with acute ischaemic stroke and UMRF were newly diagnosed with at least one new MRF, the most common being dyslipidaemia, hypertension or atrial fibrillation. Patients of the UMRF group were younger, more often smokers and on contraceptives, and had more patent-foramen-ovale-related strokes.

Stroke in the stroke unit: Recognition, treatment and outcomes in a single-centre cohort.

BACKGROUND AND PURPOSE: In-hospital strokes (IHS) are associated with longer diagnosis times, treatment delays and poorer outcomes. Strokes occurring in the stroke unit have seldom been studied. Our aim was to assess the management of in-stroke-unit ischaemic stroke (ISUS) by analysing ISUS characteristics, delays in diagnosis, treatments and outcomes. METHODS: Consecutive patients from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL), from January 2003 to June 2019, were classified as ISUS, other-IHS or community-onset stroke (COS). Baseline and stroke characteristics, time to imaging and time to treatment, missed treatment opportunities, treatment rates and outcomes were compared using multivariate analysis with adjustment for relevant clinical, imaging and laboratory data available in ASTRAL. RESULTS: Amongst the 3456 patients analysed, 138 (4.0%) were ISUS, 214 (6.2%) other-IHS and 3104 (89.8%) COS. In multivariate analysis, patients with ISUS more frequently had known stroke onset time than other-IHS (adjusted odds ratio [aOR] 2.44; 95% confidence interval [CI] 1.39-4.35) or COS (aOR 2.56; 95% CI 1.59-4.17), had fewer missed treatment opportunities than other-IHS (aOR 0.22; 95% CI 0.06-0.86) and higher endovascular treatment (EVT) rates than COS (aOR 3.03; 95% CI 1.54-5.88). ISUS was associated with a favourable shift in the modified Rankin Scale at 3 months in comparison with other-IHS (aOR 1.73; 95% CI 1.11-2.69) or COS (aOR 1.46; 95% CI 1.00-2.12). CONCLUSION: In-stroke-unit ischaemic stroke more frequently had known stroke onset time than other-IHS or COS, fewer missed treatment opportunities than other-IHS and a higher EVT rate than COS. This readiness to identify and treat patients in the stroke unit may explain the better long-term outcome of ISUS.

Rare stroke mechanisms in 4154 consecutive patients: causes, predictors, treatment, and outcomes.

BACKGROUND: Rare mechanisms of stroke (RMS) in acute ischemic stroke (AIS) have rarely been studied applying a systematic approach. Our aim was to define the frequency, etiologies, predictors, and outcomes of RMS in a consecutive series of AIS. METHODS: Data from consecutive patients from 2003 to 2016 were derived from the Acute STroke Registry and Analysis of Lausanne (ASTRAL). Frequency of subcategories of RMS was calculated. In a case-control design, RMS were compared to strokes of all other mechanisms. Outcome was assessed with 3-month Rankin-shift and 12-month mortality and recurrence rates. RESULTS: Out of 4154 AISs, 222 (5.3%) were found to have a RMS (42.0% female, median age 66 years). The most frequent RMS etiologies were medical interventions (25.6%), active oncological disease (22.5%), and vasculitis (11.7%). In multivariate analysis, RMS patients were younger, had more preceding and bilateral strokes, and a higher admission temperature. They were associated with less traditional risk factors and more systemic disease (such as AIDS, coagulopathy, and cancer). RMS also had more early ischemic changes on plain CT, less revascularization treatments, and more symptomatic hemorrhagic transformations. They presented significantly higher 3-month disability (Rankin-shift-ORadj 1.74), 12-month recurrence (ORadj 1.99), and mortality rates (ORadj 2.41). CONCLUSIONS: RMS occurred in 5.3% of a large population of consecutive AISs and are most frequently related to medical interventions, cancer, and vasculitis. RMS patients have less traditional risk factors but more systemic comorbidities, hemorrhagic transformations, recurrences, and a worse long-term outcome. Identification of RMS has direct implications for early treatment and long-term outcome.

Procedural Complications During Early Versus Late Endovascular Treatment in Acute Stroke: Frequency and Clinical Impact.

BACKGROUND AND PURPOSE: Endovascular treatment (EVT) in acute ischemic stroke is effective in the late time window in selected patients. However, the frequency and clinical impact of procedural complications in the early versus late time window has received little attention. METHODS: We retrospectively studied all acute ischemic strokes from 2015 to 2019 receiving EVT in the Acute Stroke Registry and Analysis of Lausanne. We compared the procedural EVT complications in the early (<6 hours) versus late (6-24 hours) window and correlated them with short-term clinical outcome. RESULTS: Among 695 acute ischemic strokes receiving EVT (of which 202 were in the late window), 113 (16.3%) had at least one procedural complication. The frequency of each single, and for overall procedural complications was similar for early versus late EVT (16.2% versus 16.3%, Padj=0.90). Procedural complications lead to a significantly less favorable short-term outcome, reflected by the absence of National Institutes of Health Stroke Scale improvement in late EVT (delta-National Institutes of Health Stroke Scale-24 hours, -2.5 versus 2, Padj=0.01). CONCLUSIONS: In this retrospective analysis of consecutive EVT, the frequency of procedural complications was similar for early and late EVT patients but very short-term outcome seemed less favorable in late EVT patients with complications.

Acute ischaemic stroke in the absence of established vascular risk factors: Patient characteristics, stroke mechanism and long-term outcome.

BACKGROUND AND PURPOSE: Some acute ischaemic stroke (AIS) patients do not display established vascular risk factors (EVRFs). The aim was to assess their clinical characteristics, stroke subtype etiological classification and long-term outcome. METHODS: All consecutive AIS patients from the Acute Stroke Registry of Lausanne (2003-2018) were retrospectively analyzed with complete assessment of the following EVRFs: hypertension, diabetes, major cardioembolic sources, dyslipidemia, smoking, obesity, alcohol abuse, previous stroke/transient ischaemic attack and depression/psychosis. Patients without EVRFs were compared to patients with one or more EVRFs using appropriate statistical models. RESULTS: Of 4889 included patients, 103 (2.1%) had no EVRFs. In multiple regression analysis, patients without EVRFs were significantly younger (odds ratio [OR] 0.13; 95% confidence interval [CI] 0.08-0.20) and had more multiterritorial strokes (OR 3.38; 95% CI 1.26-9.05). Strokes were more often related to patent foramen ovale (PFO) (OR 3.02; 95% CI 1.44-6.32) and less to atherosclerosis, cardioembolism or small vessel disease. In patients <55 years old, PFO (OR 2.76; 95% CI 1.50-5.08) and contraceptive use in females (OR 2.75; 95% CI 1.40-5.41) were more frequent, whereas sleep apnea syndrome (OR 0.09; 95% CI 0.01-0.63) was less. In patients ≥55 years, female sex (OR 2.84; 95% CI 1.43-5.65) and active cancer (OR 3.27; 95% CI 1.34-7.94) were more prevalent. At 12 months, patients without EVRFs had worse adjusted functional outcome (Rankin shift ORadj 0.63; 95% CI 0.42-0.95) and higher rate of recurrence and death (adjusted hazard ratio 2.11; 95% CI 1.19-3.74). CONCLUSIONS: In a consecutive cohort of AIS patients, only 2% showed no EVRFs. PFO and contraceptive use exhibited a strong association with the absence of EVRFs in younger patients and female sex and active cancer in elderly patients. Our findings highlight the importance of searching for previously unknown risk factors and/or unusual stroke mechanisms in patients without EVRFs.

External Performance of the HAVOC Score for the Prediction of New Incident Atrial Fibrillation.

Background and Purpose- The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0-4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods- In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results- In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0-4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37-3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%-73.3%). Conclusions- The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.

Supraventricular Extrasystoles on Standard 12-lead Electrocardiogram Predict New Incident Atrial Fibrillation after Embolic Stroke of Undetermined Source: The AF-ESUS Study.

BACKGROUND: The diagnosis of covert atrial fibrillation (AF) remains a major challenge to guide secondary prevention of patients with embolic stroke of undetermined source (ESUS). AIMS: We analyzed consecutive ESUS patients from 3 prospective stroke registries to assess whether the presence of supraventricular extrasystoles (SVE) on standard 12-lead electrocardiogram (ECG) is associated with the detection of AF (primary outcome), stroke recurrence and death (secondary outcomes) during follow-up. METHODS: We measured the number of SVEs in all available ECGs of patients hospitalized for ESUS. Multivariate stepwise regression with forward selection of covariates assessed the association between SVE (classified in 4 groups according to their number per 10 seconds of ECG: no SVE, >0-1SVEs, >1-2SVEs, and >2SVEs) and outcomes during follow-up. The Kaplan-Meier product limit method estimated the 10-year cumulative probabilities of outcomes in each SVE group. We calculated the negative prognostic value (NPV) of the presence of any SVE to predict new AF, defined as the probability that AF will not be detected during follow-up if there is no SVE. RESULTS: Among 853 ESUS patients followed for 2857 patient-years (median age: 67 years, 43.0% women), 226 (26.5%) patients had at least 1 SVE at the standard 12-lead ECGs performed during hospitalization. AF was detected in 125 (14.7%) of patients in the overall population during follow-up: 8.9%, 22.5%, 28.1%, and 48.3% in patients with no SVE, greater than 0-1SVE, greater than 1-2SVE and greater than 2SVE respectively. In multivariate regression analysis, compared to patients with no SVEs, the corresponding hazard-ratios were 1.80 [95% confidence intervals (95%CI):1.06-3.05], 2.26 (95%CI:1.28-4.01) and 3.19 (95%CI:1.93-5.27). The NPV of the presence of any SVE for the prediction of new AF was 91.4%. There was no statistically significant association of SVE with the risk of ischemic stroke recurrence and death. CONCLUSIONS: In ESUS patients without SVEs during hospitalization, the probability that AF will not be detected during a follow-up of 3.4 years is more than 91%.

Associated Factors and Long-Term Prognosis of 24-Hour Worsening of Arterial Patency After Ischemic Stroke.

Background and Purpose- Early arterial recanalization in acute ischemic stroke is strongly associated with better outcomes. However, early worsening of arterial patency was seldom studied. We investigated potential predictors and long-term prognosis of worsening of arterial patency at 24 hours after stroke onset. Methods- Patients from the Acute Stroke Registry and Analysis of Lausanne registry including admission and 24-hour vascular imaging (computed tomography or magnetic resonance angiography) were included. Worsening of arterial patency was defined as a new occlusion and significant stenosis in any extracranial or intracranial artery, comparing 24 hours with admission imaging. Variables associated with worsening of arterial patency were assessed by stepwise multiple logistic regression. The impact of arterial worsening on 3-month outcome was investigated with an adjusted modified Rankin Scale shift analysis. Results- Among 2152 included patients, 1387 (64.5%) received intravenous thrombolysis and endovascular treatment, and 65 (3.0%) experienced 24-hour worsening of arterial patency. In multivariable analysis, history of hypertension seemed protective (adjusted odds ratio [aOR], 0.45; 95% CI, 0.27-0.75) while higher admission National Institutes of Health Stroke Scale (aOR, 1.06; 95% CI, 1.02-1.10), intracranial (aOR, 4.78; 95% CI, 2.03-11.25) and extracranial stenosis (aOR, 3.67; 95% CI, 1.95-6.93), and good collaterals (aOR, 3.71; 95% CI, 1.54-8.95) were independent predictors of worsening of arterial patency. Its occurrence was associated with a major unfavorable shift in the distribution of the modified Rankin Scale at 3 months (aOR, 5.97; 95% CI, 3.64-9.79). Conclusions- Stroke severity and admission vascular imaging findings may help to identify patients at a higher risk of developing worsening of arterial patency at 24 hours. The impact of worsening of arterial patency on long-term outcome warrants better methods to detect and prevent this early complication.

Twenty-Four-Hour Reocclusion After Successful Mechanical Thrombectomy: Associated Factors and Long-Term Prognosis.

Background and Purpose- Early arterial recanalization is a strong determinant of prognosis in acute ischemic stroke. Nevertheless, reocclusion can occur after initial recanalization. We assessed associated factors and long-term prognosis of reocclusion after successful mechanical thrombectomy (MT). Methods- From the prospectively constructed Acute Stroke Registry and Analysis of Lausanne cohort, we included consecutive patients with anterior and posterior circulation strokes treated by successful MT (modified treatment in cerebral infarction 2b-3) and with 24-hour vascular imaging available. Reocclusion at this time-point was defined as new intracranial occlusion within an arterial segment recanalized at the end of MT. Through multivariate logistic regression, we investigated associated factors and 3-months outcome. In a 4:1 matched-cohort, we also assessed the role of residual thrombus or stenosis on post-recanalization angiographic images as potential predictor of reocclusion. Results- Among 473 patients with successful recanalization, 423 (89%) were included. Of these, 28 (6.6%) had 24-hour reocclusion. Preadmission statin therapy (aOR [adjusted odds ratio], 0.27; 95% CI, 0.08-0.94), intracranial internal carotid artery occlusion (aOR, 3.53; 95% CI, 1.50-8.32), number of passes (aOR, 1.31; 95% CI, 1.06-1.62), transient reocclusion during MT (aOR, 8.55; 95% CI, 2.14-34.09), and atherosclerotic cause (aOR, 3.14; 95% CI, 1.34-7.37) were independently associated with reocclusion. In the matched-cohort analysis, residual thrombus or stenosis was associated with reocclusion (aOR, 15.6; 95% CI, 4.6-52.8). Patients experiencing reocclusion had worse outcome (aOR, 5.0; 95% CI, 1.2-20.0). Conclusions- Reocclusion within 24-hours of successful MT was independently associated with statin pretreatment, occlusion site, more complex procedures, atherosclerotic cause, and residual thrombus or stenosis after recanalization. Reocclusion impact on long-term outcome highlights the need to monitor and prevent this early complication.

Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA2DS2-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA2DS2-VASc score were associated with increased risk of cerebrovascular events.

Collaterals are a major determinant of the core but not the penumbra volume in acute ischemic stroke.

PURPOSE: Determinants of early loss of ischemic tissue (core) or its prolonged survival (penumbra) in acute ischemic stroke (AIS) are poorly understood. We aimed to identify radiological associations of core and penumbra volumes on CT perfusion (CTP) in a large cohort of AIS. METHODS: In the ASTRAL registry (2003-2016), we identified consecutive AIS patients with proximal middle cerebral artery (MCA) occlusion. We calculated core and penumbra volumes using established thresholds and the mismatch ratio (MR). We graded collaterals into three categories on CT-angiography. We used clot burden score (CBS) to quantify the clot length. We related CTP volumes to radiological variables in multivariate regression analyses, adjusted for time from stroke onset to first imaging. RESULTS: The median age of the 415 included patients was 69 years (IQR = 21) and 49% were female. Median admission NIHSS was 16 (11) and median delay to imaging 2.2 h (1.9). Lower core volumes were associated with higher ASPECTS (hazard ratio = 1.08), absence of hyperdense MCA sign (HR = 0.70), higher CBS (i.e., smaller clot, HR = 1.10), and better collaterals (HR = 1.95). Higher penumbra volumes were related to lower CBS (i.e., longer clot, HR = 1.08) and proximal intracranial occlusion (HR = 1.47), but not to collaterals. Higher MR was found in absence of hyperdense MCA sign (HR = 1.28), absence of distal intracranial occlusion (HR = 1.39), and with better collaterals (HR = 0.52). CONCLUSIONS: In AIS, better collaterals were associated with lower core volumes, but not with higher penumbra volumes. This suggests a major role of collaterals in early tissue loss and their limited significance as marker of salvageable tissue.

Skiing Associated Stroke: Causes, Treatment, and Outcome.

BACKGROUND: Previous studies have described ischemic stroke temporally related to specific triggers, but only 1 series collected patients with acute ischemic stroke (AIS) following downhill skiing and all caused by cervical artery dissections. Here we describe our series of AIS temporally associated to ski practice, focusing on the frequency, pathogenesis, clinical presentation, and prognosis. METHODS: We maintained a prospective list of Skiing Associated Strokes (SASs) from 2003 to 2017. From all AIS patients included in our stroke registry Acute Stroke Registry and Analysis of Lausanne (ASTRAL) over the same period, we identified a comparison group of non-SAS patients, matched for age and gender. RESULTS: In the 12-year observation period, we identified 17 SASs (4 females, median age 51 years) and 51 matched control patients with nonski-associated strokes. Vascular risk factors, stroke features, and outcome were similar between the 2 groups. Stroke mechanism was arterial dissection in 11 of 17 SASs (65%) and in 7 of 51 control patients (14%, chi-square test: P < .05). In the other 6 cases of ski-associated stroke, etiology was cardiac embolism from atrial fibrillation in 2 patients, large vessel atherosclerosis with stenosis >50% in 1 patient, and undetermined in 3. Among the 11 patients with SAS caused by dissection, 8 reported minor falls while skiing, 1 had a major head trauma without loss of consciousness, and 2 had no traumatism (compared to preceding trauma in 29 of 147 [20%] of all other AIS caused by arterial dissection in ASTRAL, P < .01). CONCLUSIONS: Arterial dissection was a significantly more frequent stroke mechanism in SAS compared to matched controls, but other mechanisms occurred as well. Minor or moderate skiing-related trauma preceded most SAS with dissections.

Renal Function and Risk Stratification of Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods- We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results- In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions- The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

Ischemic Amnesia: Causes and Outcome.

BACKGROUND AND PURPOSE: We aimed to describe the frequency and characteristics of acute ischemic stroke and transient ischemic attacks presenting predominantly with amnesia (ischemic amnesia) and to identify clinical clues for differentiating them from transient global amnesia (TGA). METHODS: We retrospectively analyzed and described all patients presenting with diffusion-weighted imaging magnetic resonance imaging-confirmed acute ischemic stroke/transient ischemic attacks with antero- and retrograde amnesia as the main symptom over a 13.5-year period. We also compared their clinical features and stroke mechanisms with 3804 acute ischemic stroke from our ischemic stroke registry. RESULTS: Thirteen ischemic amnesia patients were identified, representing 0.2% of all patients with acute ischemic stroke/transient ischemic attack. In 69% of ischemic amnesia cases, amnesia was transient with a median duration of 5 hours. Ischemia was not considered in 39% of cases. Fifty-four percent of cases were clinically difficult to distinguish from TGA, including 15% who were indistinguishable from TGA. 1.2% of all presumed TGA patients at our center were later found to have ischemic amnesia. Amnesic strokes were more often cardioembolic, multiterritorial, and typically involved the posterior circulation and limbic system. Clinical clues were minor focal neurological signs, higher age, more risk factors, and stroke favoring circumstances. Although all patients were independent at 3 months, 31% had persistent memory problems. CONCLUSIONS: Amnesia as the main symptom of acute ischemic cerebral events is rare, mostly transient, and easily mistaken for TGA. Although clinical clues are often present, the threshold for performing diffusion-weighted imaging in acute amnesia should be low.

Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials.

BACKGROUND AND PURPOSE: Imaging biomarkers are increasingly used as selection criteria for stroke clinical trials. The goal of our study was to determine the prevalence of commonly studied imaging biomarkers in different time windows after acute ischemic stroke onset to better facilitate the design of stroke clinical trials using such biomarkers for patient selection. METHODS: This retrospective study included 612 patients admitted with a clinical suspicion of acute ischemic stroke with symptom onset no more than 24 hours before completing baseline imaging. Patients with subacute/chronic/remote infarcts and hemorrhage were excluded from this study. Imaging biomarkers were extracted from baseline imaging, which included a noncontrast head computed tomography (CT), perfusion CT, and CT angiography. The prevalence of dichotomized versions of each of the imaging biomarkers in several time windows (time since symptom onset) was assessed and statistically modeled to assess time dependence (not lack thereof). RESULTS: We created tables showing the prevalence of the imaging biomarkers pertaining to the core, the penumbra and the arterial occlusion for different time windows. All continuous imaging features vary over time. The dichotomized imaging features that vary significantly over time include: noncontrast head computed tomography Alberta Stroke Program Early CT (ASPECT) score and dense artery sign, perfusion CT infarct volume, and CT angiography collateral score and visible clot. The dichotomized imaging features that did not vary significantly over time include the thresholded perfusion CT penumbra volumes. CONCLUSIONS: As part of the feasibility analysis in stroke clinical trials, this analysis and the resulting tables can help investigators determine sample size and the number needed to screen.

Time-resolved CT assessment of collaterals as imaging biomarkers to predict clinical outcomes in acute ischemic stroke.

PURPOSE: Collateral circulation plays a pivotal role in the pathophysiology of acute ischemic stroke and is increasingly recognized as a promising biomarker for predicting the clinical outcome. However, there is no single established grading system. We designed a novel machine-learning software that allows non-invasive, objective, and quantitative assessment of collaterals according to their vascular territories. Our goal is to investigate the prognostic and predictive value of this collateral score for the prediction of acute stroke outcome. METHODS: This is a retrospective study of 135 patients with anterior circulation stroke treated with IV TPA. An equation using this collateral score (adjusting for age, baseline NIHSS, and recanalization) was derived to predict the clinical outcome (90-day mRS). The primary analyses focused on determining the prognostic value of our newly developed collateral scores. Secondary analyses examined the interrelationships between the collateral score and other variables. RESULTS: The collateral score emerged as a statistically significant prognostic biomarker for good clinical outcome (p < 0.033) among recanalized patients, but not among non-recanalized patients (p < 0.497). Our results also showed that collateral score was a predictive biomarker (p < 0.044). These results suggest that (1) patients with good collateral score derive more benefit from successful recanalization than patients with poor collateral score and (2) collateral status is inconsequential if recanalization is not achieved. CONCLUSION: Our data results reinforce the importance of careful patient selection for recanalization therapy to avoid futile recanalization. The paucity of collaterals predicts poor clinical outcome despite recanalization. On the other hand, robust collaterals warrant consideration for recanalization therapy given the better odds of good clinical outcome.

Eligibility and Predictors for Acute Revascularization Procedures in a Stroke Center.

BACKGROUND AND PURPOSE: Endovascular treatment (EVT) is a new standard of care for selected, large vessel occlusive strokes. We aimed to determine frequency of potentially eligible patients for intravenous thrombolysis (IVT) and EVT in comprehensive stroke centers. In addition, predictors of EVT eligibility were derived. METHODS: Patients from a stroke center-based registry (2003-2014), admitted within 24 hours of last proof of usual health, were selected if they had all data to determine IVT and EVT eligibility according to American Heart Association/American Stroke Association (AHA/ASA) guidelines (class I-IIa recommendations). Moreover, less restrictive criteria adapted from randomized controlled trials and clinical practice were tested. Maximum onset-to-door time windows for IVT eligibility were 3.5 hours (allowing door-to-needle delay of ≤60 minutes) and 4.5 hours for EVT eligibility (door-to-groin delay ≤90 minutes). Demographic and clinical information were used in logistic regression analysis to derive variables associated with EVT eligibility. RESULTS: A total of 2704 patients with acute ischemic stroke were included, of which 26.8% were transfers. Of all patients with stroke arriving at our comprehensive stroke center, a total proportion of 12.4% patients was eligible for IVT. Frequency of EVT eligibility differed between AHA/ASA guidelines and less restrictive approach: 2.9% versus 4.9%, respectively, of all patients with acute ischemic stroke and 10.5% versus 17.7%, respectively, of all patients arriving within <6 hours. Predictors for AHA-EVT eligibility were younger, shorter onset-to-admission delays, higher National Institutes of Health Stroke Scale (NIHSS), decreased vigilance, hemineglect, absent cerebellar signs, atrial fibrillation, smoking, and decreasing glucose levels (area under the curve=0.86). CONCLUSIONS: Of patients arriving within 6 hours at a comprehensive stroke center, 10.5% are EVT eligible according to AHA/ASA criteria, 17.7% according to criteria resembling randomized controlled trials, and twice as many patients are IVT eligible (36.2%).

Delay-sensitive and delay-insensitive deconvolution perfusion-CT: similar ischemic core and penumbra volumes if appropriate threshold selected for each.

INTRODUCTION: Perfusion-CT (PCT) processing involves deconvolution, a mathematical operation that computes the perfusion parameters from the PCT time density curves and an arterial curve. Delay-sensitive deconvolution does not correct for arrival delay of contrast, whereas delay-insensitive deconvolution does. The goal of this study was to compare delay-sensitive and delay-insensitive deconvolution PCT in terms of delineation of the ischemic core and penumbra. METHODS: We retrospectively identified 100 patients with acute ischemic stroke who underwent admission PCT and CT angiography (CTA), a follow-up vascular study to determine recanalization status, and a follow-up noncontrast head CT (NCT) or MRI to calculate final infarct volume. PCT datasets were processed twice, once using delay-sensitive deconvolution and once using delay-insensitive deconvolution. Regions of interest (ROIs) were drawn, and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in these ROIs were recorded and compared. Volume and geographic distribution of ischemic core and penumbra using both deconvolution methods were also recorded and compared. RESULTS: MTT and CBF values are affected by the deconvolution method used (p < 0.05), while CBV values remain unchanged. Optimal thresholds to delineate ischemic core and penumbra are different for delay-sensitive (145 % MTT, CBV 2 ml × 100 g(-1) × min(-1)) and delay-insensitive deconvolution (135 % MTT, CBV 2 ml × 100 g(-1) × min(-1) for delay-insensitive deconvolution). When applying these different thresholds, however, the predicted ischemic core (p = 0.366) and penumbra (p = 0.405) were similar with both methods. CONCLUSION: Both delay-sensitive and delay-insensitive deconvolution methods are appropriate for PCT processing in acute ischemic stroke patients. The predicted ischemic core and penumbra are similar with both methods when using different sets of thresholds, specific for each deconvolution method.

Improving the Prediction of Spontaneous and Post-thrombolytic Recanalization in Ischemic Stroke Patients.

BACKGROUND: Endovascular treatment for acute ischemic stroke patients was recently shown to improve recanalization rates and clinical outcome in a well-defined study population. Intravenous thrombolysis (IVT) alone is insufficiently effective to recanalize in certain patients or of little value in others. Accordingly, we aimed at identifying predictors of recanalization in patients treated with or without IVT. METHODS: In the observational Acute Stroke Registry and Analysis of Lausanne (ASTRAL) registry, we selected those stroke patients (1) with an arterial occlusion on computed tomography angiography (CTA) imaging, (2) who had an arterial patency assessment at 24 hours (CTA/magnetic resonance angiography/transcranial Doppler), and (3) who were treated with IVT or had no revascularization treatment. Based on 2 separate logistic regression analyses, predictors of spontaneous and post-thrombolytic recanalization were generated. RESULTS: Partial or complete recanalization was achieved in 121 of 210 (58%) thrombolyzed patients. Recanalization was associated with atrial fibrillation (odds ratio , 1.6; 95% confidence interval, 1.2-3.0) and absence of early ischemic changes on CT (1.1, 1.1-1.2) and inversely correlated with the presence of a significant extracranial (EC) stenosis or occlusion (.6, .3-.9). In nonthrombolyzed patients, partial or complete recanalization was significantly less frequent (37%, P < .01). The recanalization was independently associated with a history of hypercholesterolemia (2.6, 1.2-5.6) and the proximal site of the intracranial occlusion (2.5, 1.2-5.4), and inversely correlated with a decreased level of consciousness (.3, .1-.8), and EC (.3, .1-.6) and basilar artery pathology (.1, .0-.6). CONCLUSIONS: Various clinical findings, cardiovascular risk factors, and arterial pathology on acute CTA-based imaging are moderately associated with spontaneous and post-thrombolytic arterial recanalization at 24 hours. If confirmed in other studies, this information may influence patient selection toward the most appropriate revascularization strategy.

Optimal perfusion computed tomographic thresholds for ischemic core and penumbra are not time dependent in the clinically relevant time window.

BACKGROUND AND PURPOSE: This study aims to determine whether perfusion computed tomographic (PCT) thresholds for delineating the ischemic core and penumbra are time dependent or time independent in patients presenting with symptoms of acute stroke. METHODS: Two hundred seventeen patients were evaluated in a retrospective, multicenter study. Patients were divided into those with either persistent occlusion or recanalization. All patients received admission PCT and follow-up imaging to determine the final ischemic core, which was then retrospectively matched to the PCT images to identify optimal thresholds for the different PCT parameters. These thresholds were assessed for significant variation over time since symptom onset. RESULTS: In the persistent occlusion group, optimal PCT parameters that did not significantly change with time included absolute mean transit time, relative mean transit time, relative cerebral blood flow, and relative cerebral blood volume when time was restricted to 15 hours after symptom onset. Conversely, the recanalization group showed no significant time variation for any PCT parameter at any time interval. In the persistent occlusion group, the optimal threshold to delineate the total ischemic area was the relative mean transit time at a threshold of 180%. In patients with recanalization, the optimal parameter to predict the ischemic core was relative cerebral blood volume at a threshold of 66%. CONCLUSIONS: Time does not influence the optimal PCT thresholds to delineate the ischemic core and penumbra in the first 15 hours after symptom onset for relative mean transit time and relative cerebral blood volume, the optimal parameters to delineate ischemic core and penumbra.