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Background and purpose: Hierarchical clustering, a common 'unsupervised' machine‐learning algorithm, is advantageous for exploring potential underlying aetiology in particularly heterogeneous diseases. We investigated potential embolic sources in embolic stroke of undetermined source (ESUS) using a data‐driven machine‐learning method, and explored variation in stroke recurrence between clusters. Methods: We used a hierarchical k‐means clustering algorithm on patients' baseline data, which assigned each individual into a unique clustering group, using a minimum‐variance method to calculate the similarity between ESUS patients based on all baseline features. Potential embolic sources were categorised into atrial cardiopathy, atrial fibrillation, arterial disease, left ventricular disease, cardiac valvulopathy, patent foramen ovale (PFO) and cancer. Results: Among 800 consecutive ESUS patients (43.3% women, median age 67 years), the optimal number of clusters was four. Left ventricular disease was most prevalent in cluster 1 (present in all patients) and perfectly associated with cluster 1. PFO was most prevalent in cluster 2 (38.9% of patients) and associated significantly with increased likelihood of cluster 2 [adjusted odds ratio: 2.69, 95% confidence interval (CI): 1.64–4.41]. Arterial disease was most prevalent in cluster 3 (57.7%) and associated with increased likelihood of cluster 3 (adjusted odds ratio: 2.21, 95% CI: 1.43–3.13). Atrial cardiopathy was most prevalent in cluster 4 (100%) and perfectly associated with cluster 4. Cluster 3 was the largest cluster involving 53.7% of patients. Atrial fibrillation was not significantly associated with any cluster. Conclusions: This data‐driven machine‐learning analysis identified four clusters of ESUS that were strongly associated with arterial disease, atrial cardiopathy, PFO and left ventricular disease, respectively. More than half of the patients were assigned to the cluster associated with arterial disease. [ABSTRACT FROM AUTHOR]

Incorporation of tetracycline into dental enamel was studied by exposing presoftened enamel slabs to tetracycline-containing mineralizing solutions. Tetracycline was incorporated only when remineralization (assessed by hardness) occurred and the experimental conditions favored the formation of a soluble tetracycline- Ca complex. The fluorescence induced by tetracycline incorporation into the enamel slabs was comparable to that reported under in vivo conditions. [ABSTRACT FROM AUTHOR]

A technique is described for testing the cariogrenicity of various foodstuffs. With this method various attack can be observed in its early and clinically undetectable stages. [ABSTRACT FROM AUTHOR]

The article investigates whether a 2% sodium fluoride solution can liquefy alginate compounds by reversing the chemical reaction that sets them. Several experiments are described and their results are discussed. The sodium fluoride solution was found to liquefy hardened alginate impression compound. By adding the solution to alginate compound instead of water, setting was delayed.

The article presents research which examined the role of ascorbic acid in the mineralization of dental plaque and the solubility of dental enamel. Details are provided about the chemical role of ascorbic acid and its effect on enamel slabs and experimental plaque formed on Mylar strips. The mineralization of plaque and the hardness of the enamel were measured following exposure to ascorbic acid.

The article focuses on a study of carbonates' effect on the acid solubility rate of dental enamel. Research methods include the use of cattle teeth that were de-mineralized and re-mineralized with a solution of pure apatite or one enriched with carbonate ions. The conclusion is that remineralization in the carbonate solution makes the enamel material more resistant to acid attack.

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., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: The Bethesda category III, AUS/FLUS, comprises a heterogeneous group of thyroid lesions with variable risk of malignancy (ROM). This study evaluates ROM in two subgroups of this category based on nuclear atypia and architectural atypia., Methods: Cases in Bethesda category III were reported based on nuclear atypia (AUS) and architectural atypia (FLUS). ROM was calculated by comparing the cytologic diagnosis to the follow-up histologic diagnosis., Results: Among the 610 Bethesda category III cases in this study, 306 (50.2%) and 304 (49.8%) cases were reported as AUS and FLUS, respectively. One hundred and eighty six of 306 AUS (60.8%) and 193 of 304 FLUS (63.5%) cases underwent surgical intervention. ROM of the cases in Bethesda category III was 12.8% if all cases were counted and 20.6% if only surgical cases were counted. When analyzing separately, ROM of AUS cases was 17.0% and 28.0% with all cases and surgical cases only, respectively. For FLUS cases, ROM was 8.6% and 13.5% with all cases and surgical cases only, respectively., Conclusion: In Bethesda category III, ROM in the cases with nuclear atypia was significantly higher than the cases with architectural atypia. Sub-classifying the Bethesda Category III cases with nuclear atypia and architectural atypia, respectively may better stratify the ROM., (© 2023 Wiley Periodicals LLC.)

Distal renal tubular acidosis (dRTA) is an extremely rare disease that affects the distal tubule's ability to excrete proton cations, acidify urine, and maintain the acid-base balance. The clinical presentation of dRTA typically includes normal anion gap metabolic acidosis with decreased serum bicarbonate levels, hypokalemia, hypercalcemia, nephrocalcinosis, and alkaline urine. Hereditary causes of dRTA include pathogenic variants in ATP6V1B1 , ATP6V0A4 , SLC4A1 , FOXI1 , and WDR72 genes, which encode different transmembrane proteins on the apical surface of type A intercalated cells in the distal tubule. Variants in these genes lead to various defects in the function of the encoded proteins and can also account for extrarenal manifestations of dRTA due to the expression of these proteins in other organs, such as the stria vascularis of the inner ear. However, the literature on extrarenal manifestations, associated renal complications of hereditary dRTA, and appropriate investigations, and follow-up for patients with dRTA is scarce. In this article, we present a challenging case of neonatal-onset dRTA and contribute two novel variants of the ATP6V0A4 gene and a novel phenotype associated with a pathogenic variant on ATP6V0A4 to the scientific community. We also review the existing literature on hereditary causes of dRTA, with emphasis on associated renal and extrarenal complications., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

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., (© 2023 American Academy of Neurology.)

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.

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-OR adj 1.74), 12-month recurrence (OR adj 1.99), and mortality rates (OR adj 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., (© 2022. The Author(s).)

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., (© 2022 European Academy of Neurology.)

Background: Stroke incidence and case-fatality are reported to decline in high-income countries during the last decades. Epidemiological studies are important for health services to organize prevention and treatment strategies., Aims: The aim of this population-based study was to determine temporal trends of stroke incidence and case-fatality rates of first-ever stroke in Arcadia, a prefecture in southern Greece., Methods: All first-ever stroke cases in the Arcadia prefecture were ascertained using the same standard criteria and multiple overlapping sources in three study periods: from November 1993 to October 1995; 2004; and 2015-2016. Crude and age-adjusted to European population incidence rates were compared using Poisson regression. Twenty-eight days case fatality rates were estimated and compared using the same method., Results: In total, 1315 patients with first-ever stroke were identified. The age-standardized incidence to the European population was 252 per 100,000 person-years (95% CI 231-239) in 1993/1995, 252 (95% CI 223-286) in 2004, and 211 (192-232) in 2015/2016. The overall age- and sex-adjusted incidence rates fell by 16% (incidence rates ratio 0.84, 95% CI: 0.72-0.97). Similarly, 28-day case-fatality rate decreased by 28% (case fatality rate ratio = 0.72, 95% CI: 0.58-0.90)., Conclusions: This population-based study reports a significant decline in stroke incidence and mortality rates in southern Greece between 1993 and 2016.

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.

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.

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.

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 (CI 95% ) 1.97-5.62); and multivariable (adjusted OR 2.95; CI 95% 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.

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%., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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.

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.

Background We aimed to assess the prevalence and degree of overlap of potential embolic sources (PES) in patients with embolic stroke of undetermined source (ESUS). Methods and Results In a pooled data set derived from 3 prospective stroke registries, patients were categorized in ≥1 groups according to the PES that was/were identified. We categorized PES as follows: atrial cardiopathy, atrial fibrillation diagnosed during follow-up, arterial disease, left ventricular disease, cardiac valvular disease, patent foramen ovale, and cancer. In 800 patients with ESUS (43.1% women; median age, 67.0 years), 3 most prevalent PES were left ventricular disease, arterial disease, and atrial cardiopathy, which were present in 54.4%, 48.5%, and 45.0% of patients, respectively. Most patients (65.5%) had >1 PES, whereas only 29.7% and 4.8% of patients had a single or no PES, respectively. In 31.1% of patients, there were ≥3 PES present. On average, each patient had 2 PES (median, 2). During a median follow-up of 3.7 years, stroke recurrence occurred in 101 (12.6%) of patients (23.3 recurrences per 100 patient-years). In multivariate analysis, the risk of stroke recurrence was higher in the atrial fibrillation group compared with other PES, but not statistically different between patients with 0 to 1, 2, or ≥3 PES. Conclusions There is major overlap of PES in patients with ESUS. This may possibly explain the negative results of the recent large randomized controlled trials of secondary prevention in patients with ESUS and offer a rationale for a randomized controlled trial of combination of anticoagulation and aspirin for the prevention of stroke recurrence in patients with ESUS. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02766205.

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.

Background and Purpose: Perfusion CT may improve the diagnostic performance of noncontrast CT in acute ischemic stroke. We assessed predictors of focal hypoperfusion in acute ischemic stroke and perfusion CT performance in predicting infarction on follow-up imaging., Materials and Methods: Patients from the Acute STroke Registry and Analysis of Lausanne data base with acute ischemic stroke and perfusion CT were included. Clinical and radiologic data were collected. We identified predictors of focal hypoperfusion using multivariate analyses., Results: From the 2216 patients with perfusion CT, 38.2% had an acute ischemic lesion on NCCT and 73.3% had focal hypoperfusion on perfusion CT. After we analyzed 104 covariates, high-admission NIHSS, visual field defect, aphasia, hemineglect, sensory deficits, and impaired consciousness were positively associated with focal hypoperfusion. Negative associations were pure posterior circulation, lacunar strokes, and anticoagulation. After integrating radiologic variables into the multivariate analyses, we found that visual field defect, sensory deficits, hemineglect, early ischemic changes on NCCT, anterior circulation, cardioembolic etiology, and arterial occlusion were positively associated with focal hypoperfusion, whereas increasing onset-to-CT delay, chronic vascular lesions, and lacunar etiology showed negative association. Sensitivity, specificity, and positive and negative predictive values of focal hypoperfusion on perfusion CT for infarct detection on follow-up MR imaging were 66.5%, 79.4%, 96.2%, and 22.8%, respectively, with an overall accuracy of 76.8%., Conclusions: Compared with NCCT, perfusion CT doubles the sensitivity in detecting acute ischemic stroke. Focal hypoperfusion is independently predicted by stroke severity, cortical clinical deficits, nonlacunar supratentorial strokes, and shorter onset-to-imaging delays. A high proportion of patients with focal hypoperfusion developed infarction on subsequent imaging, as did some patients without focal hypoperfusion, indicating the complementarity of perfusion CT and MR imaging in acute ischemic stroke., (© 2019 by American Journal of Neuroradiology.)

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.

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%)., (© 2016 American Heart Association, Inc.)

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., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)