Service delivery in acute ischemic stroke patients: Does sex matter?

BACKGROUND AND PURPOSE: Women with acute ischemic stroke (AIS) are older and have greater preexisting handicap than men. Given that these factors do not fully explain their poorer long-term outcomes, we sought to investigate potential sex differences in the delivery of acute stroke care in a large cohort of consecutive AIS patients. METHODS: We analyzed all patients from ASTRAL (Acute Stroke Registry and Analysis of Lausanne) from March 2003 to December 2019. Multivariable analyses were performed on acute time metrics, revascularization therapies, ancillary examinations for stroke workup, subacute symptomatic carotid artery revascularization, frequency of change in goals of care (palliative care), and length of hospital stay. RESULTS: Of the 5347 analyzed patients, 45% were biologically female and the median age was 74.6 years. After multiple adjustments, female sex was significantly associated with higher onset-to-door (adjusted hazard ratio [aHR] = 1.09, 95% confidence interval [CI] = 1.04-1.14) and door-to-endovascular-puncture intervals (aHR = 1.15, 95% CI = 1.05-1.25). Women underwent numerically fewer diagnostic examinations (adjusted odds ratio [aOR] = 0.94, 95% CI = 0.85-1.04) and fewer subacute carotid revascularizations (aOR = 0.69, 95% CI = 0.33-1.18), and had longer hospital stays (aHR = 1.03, 95% CI = 0.99-1.07), but these differences were not statistically significant. We found no differences in the rates of acute revascularization treatments, or in the frequency of change of goals of treatments. CONCLUSIONS: This retrospective analysis of a large, consecutive AIS cohort suggests that female sex is associated with unfavorable pre- and in-hospital time metrics, such as a longer onset-to-door and door-to-endovascular-puncture intervals. Such indicators of less effective stroke care delivery may contribute to the poorer long-term functional outcomes in female patients and require further attention.

Clinical and Demographic Characteristics, Mechanisms, and Outcomes in Patients With Acute Ischemic Stroke and Newly Diagnosed or Known Active Cancer.

BACKGROUND AND OBJECTIVES: Patients with a new diagnosis of cancer carry an increased risk of acute ischemic stroke (AIS), and this risk varies depending on age, cancer type, stage, and time from diagnosis. Whether patients with AIS with a new diagnosis of neoplasm represent a distinct subset from those with a previously known active malignancy remains unclear. We aimed to estimate the rate of stroke in patients with newly diagnosed cancer (NC) and previously known active cancer (KC) and to compare the demographic and clinical features, stroke mechanisms, and long-term outcomes between groups. METHODS: Using 2003-2021 data from the Acute STroke Registry and Analysis of Lausanne registry, we compared patients with KC with patients with NC (cancer identified during AIS hospitalization or within the following 12 months). Patients with inactive and no history of cancer were excluded. Outcomes were the modified Rankin scale (mRS) score at 3 months and mortality and recurrent stroke at 12 months. We used multivariable regression analyses to compare outcomes between groups while adjusting for important prognostic variables. RESULTS: Among 6,686 patients with AIS, 362 (5.4%) had active cancer (AC), including 102 (1.5%) with NC. Gastrointestinal and genitourinary cancers were the most frequent cancer types. Among all patients with AC, 152 (42.5%) AISs were classified as cancer related, with nearly half of these cases attributed to hypercoagulability. In multivariable analysis, patients with NC had less prestroke disability (adjusted odds ratio [aOR] 0.62, 95% CI 0.44-0.86) and fewer prior stroke/transient ischemic attack events (aOR 0.43, 95% CI 0.21-0.88) than patients with KC. Three-month mRS scores were similar between cancer groups (aOR 1.27, 95% CI 0.65-2.49) and were predominantly driven by the presence of newly diagnosed brain metastases (aOR 7.22, 95% CI 1.49-43.17) and metastatic cancer (aOR 2.19, 95% CI 1.22-3.97). At 12 months, mortality risk was higher in patients with NC vs patients with KC (hazard ratio [HR] 2.11, 95% CI 1.38-3.21), while recurrent stroke risk was similar between groups (adjusted HR 1.27, 95% CI 0.67-2.43). DISCUSSION: In a comprehensive institutional registry spanning nearly 2 decades, 5.4% of patients with AIS had AC, a quarter of which were diagnosed during or within 12 months after the index stroke hospitalization. Patients with NC had less disability and prior cerebrovascular disease, but a higher 1-year risk of subsequent death than patients with KC.

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.

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.

Intima-Media Thickness and Pulsatility Index of Common Carotid Arteries in Acute Ischaemic Stroke Patients with Diabetes Mellitus.

Ultrasonographic parameters such as the common carotid artery (CCA) pulsatility index (PI) and CCA intima-media thickness (IMT) have been associated with an increased mortality and risk of recurrent stroke, respectively. We hypothesized that these ultrasonographic parameters may be useful for monitoring diabetic patients after an acute stroke. We analysed retrospective data of consecutive acute ischaemic stroke patients from the ASTRAL registry who underwent pre-cerebral ultrasonographic evaluation within 7 days of symptom onset. We compared clinical, demographic, radiological and ultrasonographic parameters in diabetic versus non-diabetic patients (univariable and multivariable analyses) and the association of these parameters with CCA PI and CCA IMT. We analysed 1507 carotid duplex ultrasound examinations from patients with a median age of 74 years. Cardiovascular co-morbidities, including hypertension, hypercholesterolemia, obstructive sleep apnoea syndrome, higher body-mass index (BMI) and peripheral artery disease, were associated with diabetes mellitus (DM). Diabetics were more often under antiplatelet therapy and had atrial fibrillation at admission. Diabetic patients showed an increased CCA PI and IMT in line with more atherosclerotic changes on acute CTA compared to non-diabetic patients. Taking IMT as the dependent variable in a second analysis, DM, higher age, hypertension, smoking and CCA PI were associated with higher IMT. Taking CCA PI as the dependent variable in a third analysis, DM, higher age and higher NIHSS at admission were associated with higher CCA PI values. Increased IMT was also associated with higher PI. We show that CCA PI and IMT are higher in diabetic patients in the first week after an initial stroke.

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score.

BACKGROUND AND AIMS: Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. METHODS: We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. RESULTS: Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; -1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; -3 points for left ventricular ejection fraction <35%; 1 point for the presence of any supraventricular extrasystole recorded during all available 12-lead standard electrocardiograms performed during hospitalization for the ESUS; -2 points for subcortical infarct; -3 points for the presence of non-stenotic carotid plaques. The rate of new incident AF during follow-up was 1.97% among the 42.3% of the cohort who had a score of ≤0, compared to 26.9% in patients with > 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. CONCLUSIONS: The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ Unique identifier: NCT02766205.

A score to predict one-year risk of recurrence after acute ischemic stroke.

BACKGROUND: An acute ischemic stroke carries a substantial risk of further recurrences. We aimed at developing and validating a prognostic tool to predict one-year stroke recurrence after acute ischemic stroke. METHODS: An integer score was derived by Cox regression analysis on a hospital-referred cohort of 3246 acute ischemic stroke patients from Switzerland, and tested for external validity in three similar independent cohorts from Athens (n = 2495), Milan (n = 1279), and Helsinki (n = 714) by means of calibration and discrimination. RESULTS: In the derivation cohort, the recurrence rate was 7% (n = 228/3246). We developed a nine-point score comprising: previous stroke or transient ischemic attack (1-point), stroke mechanism (small vessel disease and unknown mechanism: 0-points; rare stroke mechanism: 3-points; other mechanisms: 1-point), pre-stroke antiplatelets (1-point), active malignancy (2-points), chronic cerebrovascular lesions on imaging (1-point) and absence of early ischemic changes on first imaging (1-point). In the derivation cohort, the one-year risk of re-stroke was 3.0% (95%CI 1.9-4.1) in 932 (29%) patients with a score 0-1, 7.2% (6.1-8.3) in 2038 (63%) with a score 2-4, and 19.2% (14.6-23.9) in 276 (8%) with a score ≥ 5. The score calibrated well in the Athens (recurrences = 208/2495), but not in the Helsinki (recurrences = 15/714) or Milan (recurrences = 65/1279) cohorts. The AUC was 0.67 in the derivation cohort, and 0.56, 0.70, and 0.63 in the Athens, Helsinki, and Milan cohorts, respectively. CONCLUSION: We developed a score to predict one-year stroke recurrence risk in patients with acute ischemic stroke. Since the score was not completely validated when applied to external datasets where it displayed poor to fair calibration and discrimination, additional efforts are required to ameliorate our accuracy for predicting stroke recurrence, by better refining this prognostic tool or developing new ones. Clinical and radiological markers of established cerebrovascular disease and stroke etiology were better predictors than the usual demographic vascular risk factors.

Predictors of the pulsatility index in the middle cerebral artery of acute stroke patients.

Cervical and transcranial Doppler (TCD) are widely used as non-invasive methods in the evaluation of acute ischemic stroke (AIS) patients. High-grade carotid artery stenosis induces haemodynamic changes such as collateral flow and a so-called post-stenotic flow pattern of the middle cerebral artery (MCA), which appears flattened, with a reduction of the velocity difference between systole and diastole. We studied the influence of carotid artery stenosis and other variables on the flow pattern in the MCA using the pulsatility index (PI), a quantitative TCD parameter reflecting the flow spectrum in a large of cohort AIS patients. We performed ultrasound examinations of 1825 AIS patients at the CHUV from October 2004 to December 2014. We extracted patient characteristics from the ASTRAL registry. Carotid stenosis severity was classified as < 50%, 50-70%, 70-90% and > 90%, or occlusion, according to Doppler velocity criteria. We first determined variables associated with stenosis grade. Then we performed a multivariate analysis after adjusting for baseline differences, using MCA PI as dependent variable. Carotid stenosis > 70% (- 0.07) and carotid stenosis > 90%, or occlusion (- 0.14) and left side (- 0.02) are associated with lower MCA PI values. Age (+0.006 PI units per decade), diabetes (+0.07), acute ischemic changes on initial CT (+0.03) and severe plaque morphology (+0.18) are associated with higher MCA PI values. We found a number of clinical and radiological conditions that significantly influence the PI of the MCA, including high-grade ipsilateral carotid stenosis in AIS patients. We provide for the first time a quantitative evaluation of the effect of these influencing factors from a large cohort of AIS patients.

Association of Hypertensive Intracerebral Hemorrhage with Left Ventricular Hypertrophy on Transthoracic Echocardiography.

INTRODUCTION: Arterial hypertension is the most frequent cause for spontaneous intracerebral hemorrhage (sICH) and may also cause left ventricular hypertrophy (LVH). We sought to analyze whether hypertensive sICH etiology is associated with LVH. METHODS: We analyzed consecutive patients with sICH who were admitted to our tertiary stroke center during a four-year period and underwent transthoracic echocardiography (TTE) as part of the diagnostic work-up. We defined hypertensive sICH as typical localization of hemorrhage in patients with arterial hypertension and no other identified sICH etiology. We defined an increased end-diastolic interventricular septal wall thickness of ≥11 mm on TTE as a surrogate parameter for LVH. RESULTS: Among 395 patients with sICH, 260 patients (65.8%) received TTE as part of their diagnostic work-up. The median age was 71 years (interquartile range (IQR) 17), 160 patients (61.5%) were male, the median baseline National Institute of Health Stroke Scale (NIHSS) score was 8 (IQR 13). Of these, 159 (61.2%) patients had a hypertensive sICH and 156 patients (60%) had LVH. In univariable (113/159 (71.1%) vs. 43/101 (42.6%); odds ratio (OR) 3.31; 95% confidence interval (CI95%) 1.97-5.62); and multivariable (adjusted OR 2.95; CI95% 1.29-6.74) analysis, hypertensive sICH was associated with LVH. CONCLUSIONS: In patients with sICH, LVH is associated with hypertensive bleeding etiology. Performing TTE is meaningful for diagnosis of comorbidities and clarification of bleeding etiology in these patients. Future studies should include long-term outcome parameters and assess left ventricular mass as main indicator for LVH.

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.

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.

Determining factors of better leptomeningeal collaterals: a study of 857 consecutive acute ischemic stroke patients.

BACKGROUND: In acute ischemic stroke (AIS) collaterals correlate with infarct size, recanalization rate and clinical outcome. We aimed to identify factors associated with better collateral status in a large series of AIS patients with middle cerebral artery (MCA) occlusion. METHODS: In the Acute STroke Registry and Analysis of Lausanne (ASTRAL) from 2003 to 2016, we identified all consecutive AIS with proximal MCA occlusion on CT-angiography performed < 24 h. Collaterals were scored from 0 (absent) to 3 (≥ 100%) and related to multiple demographic, clinical, metabolic and radiological variables in a multivariate regression analysis (MVA). RESULTS: The 857 included patients had a median age of 72.3 years, 48.4% were female and median admission NIHSS was 16. Better collaterals were associated with younger age (OR 0.99; 95% CI 0.98-1.00), hemineglect (OR 1.35; 95% CI 1.03-1.76), absence of visual field defects (OR 0.64; 95% CI 0.46-0.90), eye deviation (OR 0.58; 95% CI 0.43-0.79) and decreased vigilance (OR 0.62; 95% CI 0.44-0.88). Better collaterals were also associated with dyslipidemia (OR 1.57; 95% CI 1.16-2.13), no previous statin use (OR 0.69; 95% CI 0.50-0.95), and lower creatinine levels (OR 0.99; 95% CI 0.99-1.00). On neuroimaging, better collaterals related to higher ASPECTS score (OR 1.27; 95% CI 1.20-1.35) and higher clot burden score (OR 1.09; 95% CI 1.03-1.14). CONCLUSIONS: Younger age, dyslipidemia and lower creatinine levels were predictors of better collaterals in AIS patients from proximal MCA occlusions. Greater degree of collaterals related to lower stroke severity on admission. On neuroimaging, better collaterals were independently associated with minor early ischemic changes and lower clot burden. These data may add knowledge on pathophysiology of collaterals development and may help to identify patients with better collaterals for late or aggressive recanalization treatments.

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.

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%).

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.

Leukoaraiosis and stroke recurrence risk in patients with and without atrial fibrillation.

OBJECTIVE: We aimed to investigate the association between leukoaraiosis and long-term risk of stroke recurrence adjusting for clinical scores developed and validated for the prediction of stroke risk, such as CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or TIA) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category). METHODS: Study population was derived from the Athens Stroke Registry and was categorized in 2 subgroups according to the presence of atrial fibrillation (AF). Cox proportional hazards analysis was performed to assess the independent predictors of stroke recurrence. To investigate whether leukoaraiosis adds to the prognostic accuracy of CHADS2 and CHA2DS2-VASc scores, we used the likelihood ratio test. Overall model assessment was performed with Nagelkerke R(2) and Harrell C statistic. Kaplan-Meier analyses were also performed. RESULTS: Among 1,892 patients, there were 320 (16.9%) with leukoaraiosis and 670 (35.4%) with AF. In the Kaplan-Meier analysis, there was significant difference in cumulative probability of stroke recurrence between patients with and without leukoaraiosis in the non-AF group (p < 0.01), but not in the AF group (p = 0.46). On Cox multivariate analysis, leukoaraiosis was found to be a significant independent predictor of stroke recurrence only in the non-AF group, in the models adjusting for CHADS2 (hazard ratio: 1.86, 95% confidence interval: 1.35-2.56) and CHA2DS2-VASc (hazard ratio: 1.82, 95% confidence interval: 1.32-2.51) scores. Leukoaraiosis was not a predictor of stroke recurrence in the AF group. Leukoaraiosis did not improve the predictive accuracy of the 2 scores, whether in the non-AF group (Harrell C statistic: 0.56 vs 0.59 [p = 0.31] for the model including CHADS2; 0.56 vs 0.59 [p = 0.44] for the model including CHA2DS2-VASc) or the AF group (Harrell C statistic: 0.63 vs 0.62 for the model including CHADS2; 0.64 vs 0.64 for the model including CHA2DS2-VASc). CONCLUSIONS: Leukoaraiosis is an independent predictor of stroke recurrence in non-AF stroke patients. However, leukoaraiosis did not increase the accuracy of the CHADS2 and CHA2DS2-VASc scores to predict stroke recurrence in AF or non-AF stroke patients.

ASTRAL-R score predicts non-recanalisation after intravenous thrombolysis in acute ischaemic stroke.

Intravenous thrombolysis (IVT) as treatment in acute ischaemic strokes may be insufficient to achieve recanalisation in certain patients. Predicting probability of non-recanalisation after IVT may have the potential to influence patient selection to more aggressive management strategies. We aimed at deriving and internally validating a predictive score for post-thrombolytic non-recanalisation, using clinical and radiological variables. In thrombolysis registries from four Swiss academic stroke centres (Lausanne, Bern, Basel and Geneva), patients were selected with large arterial occlusion on acute imaging and with repeated arterial assessment at 24 hours. Based on a logistic regression analysis, an integer-based score for each covariate of the fitted multivariate model was generated. Performance of integer-based predictive model was assessed by bootstrapping available data and cross validation (delete-d method). In 599 thrombolysed strokes, five variables were identified as independent predictors of absence of recanalisation: Acute glucose > 7 mmol/l (A), significant extracranial vessel STenosis (ST), decreased Range of visual fields (R), large Arterial occlusion (A) and decreased Level of consciousness (L). All variables were weighted 1, except for (L) which obtained 2 points based on ß-coefficients on the logistic scale. ASTRAL-R scores 0, 3 and 6 corresponded to non-recanalisation probabilities of 18, 44 and 74 % respectively. Predictive ability showed AUC of 0.66 (95 %CI, 0.61-0.70) when using bootstrap and 0.66 (0.63-0.68) when using delete-d cross validation. In conclusion, the 5-item ASTRAL-R score moderately predicts non-recanalisation at 24 hours in thrombolysed ischaemic strokes. If its performance can be confirmed by external validation and its clinical usefulness can be proven, the score may influence patient selection for more aggressive revascularisation strategies in routine clinical practice.