Cerebral collaterals are associated with pre-treatment brain-blood barrier permeability in acute ischemic stroke patients.

INTRODUCTION: To investigate the relationship between collaterals and blood-brain barrier (BBB) permeability on pre-treatment MRI in a cohort of acute ischemic stroke (AIS) patients treated with thrombectomy. METHODS: We conducted a retrospective analysis of the HIBISCUS-STROKE cohort, a single-center observational study that enrolled patients treated with thrombectomy from 2016 to 2022. Dynamic-susceptibility MRIs were post-processed to generate K2 maps with arrival-time correction, which were co-registered with apparent diffusion coefficient (ADC) maps. The 90th percentile of K2 was extracted from the infarct core-defined by an ADC ≤ 620 × 10-6 mm2/s with manual adjustments-and expressed as a percentage change compared to the contralateral white matter. Collaterals were assessed using pre-thrombectomy digital subtraction arteriography with an ASITN/SIR score < 3 defining poor collaterals. RESULTS: Out of 249 enrolled, 101 (40.6%) were included (median age: 72.0 years, 52.5% of males, median NIHSS score at admission: 15.0). Patients with poor collaterals (n = 44) had worse NIHSS scores (median: 16.0 vs 13.0, p = 0.04), larger infarct core volumes (median: 43.7 mL vs 9.5 mL, p < 0.0001), and higher increases in K2 (median: 346.3% vs 152.7%, p = 0.003). They were less likely to achieve successful recanalization (21/44 vs 51/57, p < 0.0001) and experienced more frequent hemorrhagic transformation (16/44 vs 9/57, p = 0.03). On multiple variable analysis, poor collaterals were associated with larger infarct cores (odds ratio (OR) = 1.12, 95% confidence interval (CI): [1.07, 1.17], p < 0.0001) and higher increases in K2 (OR = 6.63, 95% CI: [2.19, 20.08], p = 0.001). CONCLUSION: Poor collaterals are associated with larger infarct cores and increased BBB permeability at admission MRI. CLINICAL RELEVANCE STATEMENT: Poor collaterals are associated with a larger infarct core and increased BBB permeability at admission MRI of AIS patients treated with thrombectomy. These findings may have translational interests for extending thrombolytic treatment eligibility and developing neuroprotective strategies. KEY POINTS: In AIS, collaterals and BBB disruption have been both linked to hemorrhagic transformation. Poor collaterals were associated with larger ischemic cores and increased BBB permeability on pre-treatment MRI. These findings could contribute to hemorrhagic transformation risk stratification, thereby refining clinical decision-making for reperfusion therapies.

Determinants of adherence to post-stroke/transient ischemic attack secondary prevention medications: A cohort study.

BACKGROUND: Adherence to post-stroke secondary prevention medications mitigates recurrence risk. This study aimed to measure adherence to secondary prevention medications during 3 years post-ischemic stroke/transient ischemic attack, using prescription and dispensing data, and identify factors associated with suboptimal adherence. METHODS: This multicenter, prospective, cohort study involved patients from the STROKE 69 cohort, which included all consecutive patients with suspected acute stroke admitted between November 2015 and December 2016 to any emergency department or stroke center in the Rhône area in France. Prescription data for antihypertensive agents, antidiabetic agents, lipid-lowering drugs, and antithrombotics were collected. Dispensing data were provided by the French regional reimbursement database. Adherence was calculated using the continuous medication acquisition index. Associations between suboptimal adherence and potential influencing factors across the World Health Organization's five dimensions were explored through univariate and multivariate analyses. RESULTS: From 1512 eligible patients, 365 were included. Optimal adherence to overall treatment (≥90%) was observed in 61%, 62%, and 65% of patients in the first, second, and third years, respectively. Education level (high school diploma or higher: OR = 3.24, 95% CI [1.49; 7.36]) and depression (Hospital Anxiety and Depression Scale-Depression scores 8-10: OR = 1.90, 95% CI [1.05; 3.44]) were significantly associated with suboptimal adherence. CONCLUSIONS: Overall adherence to secondary prevention medications was fairly good. Having an initial diagnosis of transient ischemic attack, a high level of education, or depression was associated with increased odds of suboptimal adherence, while having a history of heart rhythm disorder was associated with lower odds.

Brush sign and collateral supply as potential markers of large infarct growth after successful thrombectomy.

OBJECTIVES: To investigate the relationships between brush sign and cerebral collateral status on infarct growth after successful thrombectomy. METHODS: HIBISCUS-STROKE cohort includes acute ischemic stroke patients treated with thrombectomy after MRI triage and undergoing a day-6 MRI including FLAIR images to quantify final infarct volume (FIV). Successful reperfusion was defined as a modified thrombolysis in cerebral infarction score ≥ 2B. Infarct growth was calculated by subtracting FIV from baseline ischemic core after co-registration and considered large (LIG) when > 11.6 mL. Brush sign was assessed on T2*-weighted-imaging and collaterals were assessed using the hypoperfusion intensity ratio, which is the volume of Time-To-Tmax (Tmax) ≥ 10 s divided by the volume of Tmax ≥ 6 s. Good collaterals were defined by a hypoperfusion intensity ratio < 0.4. RESULTS: One hundred and twenty-nine patients were included, of whom 45 (34.9%) had a brush sign and 63 (48.8%) good collaterals. Brush sign was associated with greater infarct growth (p = 0.01) and larger FIV (p = 0.02). Good collaterals were associated with a smaller baseline ischemic core (p < 0.001), larger penumbra (p = 0.04), and smaller FIV (p < 0.001). Collateral status was not significantly associated with brush sign (p = 0.20) or with infarct growth (p = 0.67). Twenty-eight (22.5%) patients experienced LIG. Univariate regressions indicated that brush sign (odds ratio (OR) = 4.8; 95% confidence interval (CI): [1.9;13.3]; p = 0.004) and hemorrhagic transformation (OR = 1.7; 95%CI: [1.2;2.6]; p = 0.04) were predictive of LIG. In multivariate regression, only the brush sign remained predictive of LIG (OR = 5.2; 95%CI: [1.8-16.6], p = 0.006). CONCLUSIONS: Brush sign is a predictor of LIG after successful thrombectomy and cerebral collateral status is not. KEY POINTS: • Few predictors of ischemic growth are known in ischemic stroke patients achieving successful mechanical thrombectomy. • Our results suggest that the brush sign-a surrogate marker of severe hypoperfusion-is independently associated with large ischemic growth (> 11.6 mL) after successful thrombectomy whereas cerebral collateral status does not.

Is the optimal Tmax threshold identifying perfusion deficit volumes variable across MR perfusion software packages? A pilot study.

PURPOSE: Accurate quantification of ischemic core and ischemic penumbra is mandatory for late-presenting acute ischemic stroke. Substantial differences between MR perfusion software packages have been reported, suggesting that the optimal Time-to-Maximum (Tmax) threshold may be variable. We performed a pilot study to assess the optimal Tmax threshold of two MR perfusion software packages (A: RAPID®; B: OleaSphere®) by comparing perfusion deficit volumes to final infarct volumes as ground truth. METHODS: The HIBISCUS-STROKE cohort includes acute ischemic stroke patients treated by mechanical thrombectomy after MRI triage. Mechanical thrombectomy failure was defined as a modified thrombolysis in cerebral infarction score of 0. Admission MR perfusion were post-processed using two packages with increasing Tmax thresholds (≥ 6 s, ≥ 8 s and ≥ 10 s) and compared to final infarct volume evaluated with day-6 MRI. RESULTS: Eighteen patients were included. Lengthening the threshold from ≥ 6 s to ≥ 10 s led to significantly smaller perfusion deficit volumes for both packages. For package A, Tmax ≥ 6 s and ≥ 8 s moderately overestimated final infarct volume (median absolute difference: - 9.5 mL, interquartile range (IQR) [- 17.5; 0.9] and 0.2 mL, IQR [- 8.1; 4.8], respectively). Bland-Altman analysis indicated that they were closer to final infarct volume and had narrower ranges of agreement compared with Tmax ≥ 10 s. For package B, Tmax ≥ 10 s was closer to final infarct volume (median absolute difference: - 10.1 mL, IQR: [- 17.7; - 2.9]) versus - 21.8 mL (IQR: [- 36.7; - 9.5]) for Tmax ≥ 6 s. Bland-Altman plots confirmed these findings (mean absolute difference: 2.2 mL versus 31.5 mL, respectively). CONCLUSIONS: The optimal Tmax threshold for defining the ischemic penumbra appeared to be most accurate at ≥ 6 s for package A and ≥ 10 s for package B. This implies that the widely recommended Tmax threshold ≥ 6 s may not be optimal for all available MRP software package. Future validation studies are required to define the optimal Tmax threshold to use for each package.

Successful thrombectomy is beneficial in patients with pre-stroke disability: Results from an international multicenter cohort study.

BACKGROUND: Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion. METHODS: Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes. RESULTS: Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048). CONCLUSION: In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

Social inequalities and gender differences in healthcare management of acute ischaemic stroke in France.

BACKGROUND AND PURPOSE: There are regional disparities in access to stroke units in France. Several studies have shown that living in disadvantaged areas is associated with a higher frequency of stroke, worse severity at presentation, increased level of dependency and higher mortality rates. However, few studies have explored the association between an individual's socioeconomic characteristics and stroke care. Our study aimed to determine if living standards are associated with stroke unit access for patients admitted to hospital for acute ischaemic stroke. METHODS: Using the EDP-Santé French administrative database, all patients admitted to hospital for acute ischaemic stroke between 2014 and 2017 were selected. Acute ischaemic stroke corresponded to hospital stay with International Classification of Diseases 10th Revision codes I63 or I64 as the main diagnosis. Multivariate logistic regression was used to identify if standard of living was associated with likelihood of admission to a stroke unit. RESULTS: In all, 14,123 acute care episodes were identified, corresponding to 335,273 episodes in the general population when appropriately weighted. Of these, 52.9% were admitted to a stroke unit. Being in the first (i.e., poorest) living standard quartile was associated with lower likelihood of admission to a stroke unit compared with the fourth (i.e., wealthiest) quartile, and was associated with a higher likelihood of paralysis and language disorder, and death at 1 year. CONCLUSION: A low living standard was associated with lower likelihood of admission to a stroke unit as well as a greater chance of paralysis and aphasia at the end of hospitalization and a higher possibility of death at 1 year after stroke. Greater access to stroke units for disadvantaged people should be promoted.

Temporal Trend of Transient Ischemic Attack Management over a 10-Year Period: Data from the Rhône County, France.

BACKGROUND: Timely recognition and management of transient ischemic attack (TIA) offer the greatest opportunity to prevent subsequent stroke. But variability of TIA management quality exists across hospitals. Under the impetus of national plans, measures were adopted to improve TIA management, including a structured local pathway. Our objective was to compare TIA management between two periods over 10 years, before and after the implementation of these measures. METHODS: A before-and-after study was conducted with two identical population-based cohort studies in 2006-2007 (AVC69) and 2015-2016 (STROKE69) including all patients with TIA diagnosis over a 7-month period in six public and private hospitals in the Rhône county in France. The primary outcome was the adequate TIA management defined as brain and vessel imaging within 24 h of admission and the prescription of antithrombotic treatment at discharge. RESULTS: We identified 109 patients TIA patients in 2006-2007, and 458 over the same period in 2015-2016. A higher proportion of patients were adequately managed in 2015-2016 compared to 2006-2007 (14/96 [15%] in 2006-2007 vs. 306/452 [68%] in 2015-2016, p < 0.001). This difference was mainly driven by a marked increase of vessel imaging performed within 24 h of admission, most often by computed tomography angiography. Furthermore, patients called more often emergency medical dispatch before admission, were admitted with a shorter delay after symptom onset, and were more likely discharged to home in 2015-2016 compared to 2006-2007. CONCLUSION: Our study demonstrated an increasing rate of adequate TIA management, mainly driven by a marked increase of vessel imaging within 24 h of admission, over a 10-year period in the Rhône county in France.

Predictors of Outcome After Mechanical Thrombectomy in Stroke Patients Aged ≥85 Years.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT. METHODS: Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0-3 or equal to pre-stroke mRS at 3 months. RESULTS: Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36-0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83-0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32-10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08-0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization. CONCLUSIONS: Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.

Co-design and evaluation of a patient-centred transition programme for stroke patients, combining case management and access to an internet information platform: study protocol for a randomized controlled trial - NAVISTROKE.

BACKGROUND: Stroke affects many aspects of life in stroke survivors and their family, and returning home after hospital discharge is a key step for the patient and his or her relatives. Patients and caregivers report a significant need for advice and information during this transition period. Our hypothesis is that, through a comprehensive, individualised and flexible support for patients and their caregivers, a patient-centred post-stroke hospital/home transition programme, combining an Internet information platform and telephone follow-up by a case manager, could improve patients' level of participation and quality of life. METHODS: An open parallel-group randomized trial will be conducted in two centres in France. We will recruit 170 adult patients who have had a first confirmed stroke, and were directly discharged home from the stroke unit with a modified Rankin score ≤3. Intervention content will be defined using a user-centred approach involving patients, caregivers, health-care professionals and social workers. Patients randomized to the intervention group will receive telephonic support by a trained case manager and access to an interactive Internet information platform during the 12 months following their return home. Patients randomized to the control group will receive usual care. The primary outcome is patient participation, measured by the "participation" dimension score of the Stroke Impact Scale 6 months after discharge. Secondary outcomes will include, for patients, quality of life, activation, care consumption, as well as physical, mental and social outcomes; and for caregivers, quality of life and burden. Patients will be contacted within one week after discharge, at 6 and 12 months for the outcomes collection. A process evaluation alongside the study is planned. DISCUSSION: Our patient-centred programme will empower patients and their carers, through individualised and progressive follow-up, to find their way around the range of available healthcare and social services, to better understand them and to use them more effectively. The action of a centralised case manager by telephone and the online platform will make it possible to disseminate this intervention to a large number of patients, over a wide area and even in cases of geographical isolation. TRIAL REGISTRATION: ClinicalTrials NCT03956160 , Posted: May-2019 and Update: September-2021.

Patent foramen ovale closure in stroke patients with migraine in the CLOSE trial. The CLOSE-MIG study.

BACKGROUND AND PURPOSE: The efficacy of patent foramen ovale (PFO) closure to reduce the frequency of migraine attacks remains controversial. METHODS: This was a planned sub-study in migraine patients enrolled in a randomized, clinical trial designed to assess the superiority of PFO closure plus antiplatelet therapy over antiplatelet therapy alone to prevent stroke recurrence in patients younger than 60 years with a PFO-associated cryptogenic ischaemic stroke. The main outcome was the mean annual number of migraine attacks in migraine patients with aura and in those without aura, as recorded at each follow-up visit by study neurologists. RESULTS: Of 473 patients randomized to PFO closure or antiplatelet therapy, 145 (mean age 41.9 years; women 58.6%) had migraine (75 with aura and 70 without aura). Sixty-seven patients were randomized to PFO closure and 78 to antiplatelet therapy. During a mean follow-up of about 5 years, there were no differences between antiplatelet-only and PFO closure groups in the mean annual number of migraine attacks, both in migraine patients with aura (9.2 [11.9] vs. 12.0 [19.1], p = 0.81) and in those without aura (12.1 [16.1] vs. 11.8 [18.4], p > 0.999). There were no differences between treatment groups regarding cessation of migraine attacks, migraine-related disability at 2 years and use of migraine-preventive drugs during follow-up. CONCLUSIONS: In young and middle-aged adults with PFO-associated cryptogenic stroke and migraine, PFO closure plus antiplatelet therapy did not reduce the mean annual number of migraine attacks compared to antiplatelet therapy alone, in migraine patients both with and without aura.

Matrix Metalloproteinase-9 and Monocyte Chemoattractant Protein-1 Are Associated With Collateral Status in Acute Ischemic Stroke With Large Vessel Occlusion.

BACKGROUND AND PURPOSE: In ischemic stroke, inflammatory status may condition the development of collateral circulation. Here we assessed the relationship between systemic inflammatory biomarkers and collateral status in large vessel occlusion before mechanical thrombectomy. METHODS: HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. MMP-9 (matrix metalloproteinase-9) and MCP-1 (monocyte chemoattractant protein-1) were measured on blood sampling collected at admission. Collateral status was assessed on pretreatment Digital subtraction angiography and categorized into poor (Higashida score, 0-2) and good (Higashida score, 3-4). A multiple logistic regression model was performed to detect independent markers of good collateral status. RESULTS: One hundred and twenty-two patients were included, of them 71 patients (58.2%) had a good collateral status. In univariate analysis, low MMP-9 levels (P=0.01), high MCP-1 levels (P<0.01), a low National Institute of Health Stroke Score (P=0.046), a high diastolic blood pressure (P=0.049), the absence of tandem occlusion (P=0.046), a high Alberta Stroke Program Early CT Score (P<0.01) and a low volume on the diffusion-weighted imaging (P<0.01) were associated with good collateral status. Following multivariate analysis, low MMP-9 levels (P=0.02) and high MCP-1 levels (P<0.01) remained associated with good collateral status. CONCLUSIONS: Low MMP-9 and high MCP-1 levels were associated with good pretreatment collateral status in patients with acute ischemic stroke with large vessel occlusion. These results might suggest a relationship between collateral status and inflammation.

Choice of Initial Brain Imaging in Patients with Suspected Acute Stroke: STROKE69, a Population-Based Study.

BACKGROUND: In patients with suspected stroke, brain imaging is recommended in the acute phase for appropriate management and treatment. Both computed tomography (CT) and magnetic resonance imaging (MRI) are considered reasonable choices for initial brain imaging. When both techniques are available, choosing one or the other might be associated with specific factors related either to patients, stroke symptoms, and severity or management organization. METHODS: The study was performed within the STROKE 69 database, a population-based cohort of all adult patients with suspected stroke admitted in one of the emergency departments (ED), primary stroke center, or stroke center of the Rhône County, from November 2015 to December 2016. Patients were included if they were admitted within 24 h following either symptom onset or last known normal. To identify factors potentially associated with the choice of initial brain imaging, a multivariate logistic regression was performed. RESULTS: Among the 3,244 patients with suspected stroke enrolled in the STROKE69 cohort, 3,107 (95.8%) underwent brain imaging within the first 24 h after admission. Among those 74.6% underwent CT as initial imaging while 25.4% had an MRI. In multivariate analyses, several factors were associated with a lower probability of having an MRI as initial brain imaging versus CT. These were either patient characteristics: older age (>80 years old, OR 0.39 [95% CI 0.28-0.54]), preexisting disability (OR 0.55 [95% CI 0.36-0.84]), use of anticoagulants (OR 0.52 [95% CI 0.33-0.81]), stroke characteristics: stroke of unknown onset (OR 0.42 [95% CI 0.31-0.58]) or factors associated with overall management: onset-to-door time (>6 h, OR 0.38 [95% CI 0.23-0.60]), initial admission to ED (OR 0.02 [95% CI 0.02-0.04]) or intensive care unit (OR 0.01 [95% CI 0.001-0.08]), personal transport (OR 0.66 [95% CI 0.45-0.96]), and admission during working hours (OR 0.65 [95% CI 0.51-0.84]). CONCLUSIONS: Besides CT or MRI availability, a number of other parameters could influence the choice of first imaging in case of stroke suspicion. These are related to patient characteristics, type of stroke symptoms, and type of organization.

Impact of a theory-informed and user-centered stroke information campaign on the public's behaviors, attitudes, and knowledge when facing acute stroke: a controlled before-and-after study.

BACKGROUND: Public awareness of stroke symptoms is a key factor to ensure access to reperfusion strategies in due time. We designed and launched a regional theory-informed and user-centered information campaign and assessed its impact on emergency medical services (EMS) calls for stroke suspicion, time-to-call, and public attitudes and awareness concerning stroke. METHODS: A controlled before-and-after study was conducted during 3 sequential time-periods in 2 separate counties. Key messages of the campaign were underpinned by stroke representations and the theory of planned behavior, and focused on recognition of stroke warning signs and the need to call EMS urgently. The campaign included posters, leaflets, adverts and films displayed in bus and subway stations, internet, social networks, and local radio. Outcome measures on behavior, attitudes, and knowledge were assessed before the launch of the campaign, at 3 months, and 12 months. RESULTS: The number of EMS calls for stroke suspicion increased by 21% at 12 months in the intervention county and this change was significantly different to that observed in the control county (p = 0.02). No significant changes were observed regarding self-reported attitudes in case of stroke. An 8% significant increase in recognizing at least 2 stroke warning signs was observed in the intervention county (p = 0.04) at 3 months, while it did not change significantly in the control county (p = 0.6). However, there was no significant difference in warning sign recognition between both counties (p = 0.16). CONCLUSION: The campaign significantly improved public's behavior of calling EMS, although stroke knowledge was not improved as much as expected. Repeating these campaigns over time might further help improve timeliness and access to reperfusion strategies. TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT02846363 .

Reprint of : Transcatheter closure of patent foramen ovale to prevent stroke recurrence in patients with otherwise unexplained ischaemic stroke: Expert consensus of the French Neurovascular Society and the French Society of Cardiology.

BACKGROUND: Unlike previous randomized clinical trials (RCTs), recent trials and meta-analyses have shown that transcatheter closure of patent foramen ovale (PFO) reduces stroke recurrence risk in young and middle-aged adults with an otherwise unexplained PFO-associated ischaemic stroke. AIM: To produce an expert consensus on the role of transcatheter PFO closure and antithrombotic drugs for secondary stroke prevention in patients with PFO-associated ischaemic stroke. METHODS: Five neurologists and five cardiologists with extensive experience in the relevant field were nominated by the French Neurovascular Society and the French Society of Cardiology to make recommendations based on evidence from RCTs and meta-analyses. RESULTS: The experts recommend that any decision concerning treatment of patients with PFO-associated ischaemic stroke should be taken after neurological and cardiological evaluation, bringing together the necessary neurovascular, echocardiography and interventional cardiology expertise. Transcatheter PFO closure is recommended in patients fulfilling all the following criteria: age 16-60 years; recent (≤6 months) ischaemic stroke; PFO associated with atrial septal aneurysm (>10mm) or with a right-to-left shunt>20 microbubbles or with a diameter≥2mm; PFO felt to be the most likely cause of stroke after thorough aetiological evaluation by a stroke specialist. Long-term oral anticoagulation may be considered in the event of contraindication to or patient refusal of PFO closure, in the absence of a high bleeding risk. After PFO closure, dual anti-platelet therapy with aspirin (75mg/day) and clopidogrel (75mg/day) is recommended for 3 months, followed by monotherapy with aspirin or clopidogrel for≥5 years. CONCLUSIONS: Although a big step forward that will benefit many patients has been taken with recent trials, many questions remain unanswered. Pending results from further studies, decision-making regarding management of patients with PFO-associated ischaemic stroke should be based on a close coordination between neurologists/stroke specialists and cardiologists.

Does Small Vessel Disease Burden Impact Collateral Circulation in Ischemic Stroke Treated by Mechanical Thrombectomy?

Background and Purpose- The development of leptomeningeal collateral artery network might be adversely affected by small vessel wall alteration. We sought to determine whether small vessel disease (SVD) burden may impact collateral development in patients treated by mechanical thrombectomy for anterior circulation acute ischemic stroke. Methods- The patients admitted in our center for anterior circulation acute ischemic stroke and (1) treated by mechanical thrombectomy with or without thrombolysis and (2) who underwent a baseline magnetic resonance imaging were included in the study. The SVD burden and the pial collaterality were assessed through the cerebral SVD score (severe when ≥1) and the Higashida score (favorable when ≥ 3) on magnetic resonance imaging and digital subtraction angiography, respectively. Any association between the cerebral SVD score and the collaterality were assessed through comparative and regression analyses. Results- Between January 2013 and March 2018, 240 patients met the inclusion criteria (68.7±16.1 years old; 49.2 % female). The cerebral SVD scores were of 0 in 125 (52.1%), 1 in 74 (30.8%), 2 in 30 (12.5%), and 3 in 11 (4.6%) patients. Hundred and thirty-six patients (58.1%) presented a favorable collaterality score. The favorable collaterality subgroup presented a significantly higher proportion of female (79%), lower baseline National Institutes of Health Stroke Scale ( P<0.001), and higher Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Scores ( P<0.001). The regression analyses showed no impact of the cerebral SVD score on the collaterality pattern (odds ratio, 1.11, 95% CI, 0.82-1.50; P=0.51). Conclusions- In patients with anterior circulation acute ischemic stroke, collateral flow status does not seem to be influenced by SVD burden.

Comparison of classification methods for tissue outcome after ischaemic stroke.

In acute ischaemic stroke, identifying brain tissue at high risk of infarction is important for clinical decision-making. This tissue may be identified with suitable classification methods from magnetic resonance imaging data. The aim of the present study was to assess and compare the performance of five popular classification methods (adaptive boosting, logistic regression, artificial neural networks, random forest and support vector machine) in identifying tissue at high risk of infarction on human voxel-based brain imaging data. The classification methods were used with eight MRI parameters, including diffusion-weighted imaging and perfusion-weighted imaging obtained in 55 patients. The five criteria used to assess the performance of the methods were the area under the receiver operating curve (AUCroc ), the area under the precision-recall curve (AUCpr ), sensitivity, specificity and the Dice coefficient. The methods performed equally in terms of sensitivity and specificity, while the results of AUCroc and the Dice coefficient were significantly better for adaptive boosting, logistic regression, artificial neural networks and random forest. However, there was no statistically significant difference between the performances of these five classification methods regarding AUCpr , which was the main comparison metric. Machine learning methods can provide valuable prognostic information using multimodal imaging data in acute ischaemic stroke, which in turn can assist in developing personalized treatment decision for clinicians after a thorough validation of methods with an independent data set.

Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is an uncommon neurological condition usually treated with heparin followed by oral vitamin K antagonists (VKAs). In patients with venous thromboembolism (VTE), compared to VKAs, direct oral anticoagulants (DOACs) offer several advantages. However, there is little data concerning their use in managing CVT. AIMS: This retrospective observational study pursued 2 objectives: (1) to investigate clinical characteristics of CVT patients treated with heparin + DOACs vs. heparin + standard treatment; (2) to compare clinical outcomes. METHODS: Consecutive CVT patients recruited from January 2016 to March 2018 in 2 French university hospitals (Lyon, Saint-Etienne), and treated with DOACs or VKAs were identified. Radiological evolution, VTE, hemorrhagic events, and antithrombotic medication were recorded. Functional outcome was assessed by the modified Rankin scale score and venous recanalization was assessed by magnetic resonance imaging. RESULTS: Overall, 41 patients were included: 25 (61%) received VKAs and 16 (39%) DOACs. We identified no clinical or radiological features explaining the physicians' preference for a specific anticoagulation treatment, and age, initial clinical presentation, radiological severity, and individual risk factors thus unlikely guided the choice of anticoagulant. No DOAC patient exhibited clinical or radiological thrombosis aggravation, and the thrombosis completely vanished in 6 (40%). Two of the VKA-treated patients (28.6%) demonstrated complete venous recanalization, whereas 3 others experienced clinical or radiological aggravation versus baseline. There was no major bleeding leading to hospitalization in both groups. CONCLUSION: The collected data on DOAC efficacy and safety in CVT management appear encouraging, yet needs to be confirmed by larger prospective randomized clinical trials.

Sex-Related Differences in Management and Outcome of Acute Ischemic Stroke in Eligible Patients to Thrombolysis.

BACKGROUND: Literature has highlighted sex-based differences in the natural course of stroke and in response to treatment with intravenous tissue plasminogen activator (tPA). OBJECTIVES: We aimed to compare the management and outcome of acute ischemic stroke (AIS) among women and men on a French registry based on a federated network of emergency physicians and neurologists. METHOD: We included 2,790 patients received tPA between 2010 and 2016 from the stroke centers in the RESUVal area. We provided age-adjusted analysis and multivariate models for determining the role of sex in the outcome measures. RESULTS: After age-adjustment, women presented more moderate to severe stroke at admission with more proximal occlusions. Among tPA eligible patients, the therapeutic strategy and in-hospital hemorrhagic complications were proportionally identical whatever the sex. The total ischemic time from onset symptom to thrombolysis did not differ from women to men. Age-adjusted 3-month mortality did not differ between women and men, and the determinants of mortality were age (relative risk [RR] 1.56 [1.37-1.78], p < 0.0001), proximal occlusion (RR 2.5 [1.88-3.33], p < 0.0001), and at least one complication (RR 2.43 [1.89-3.13], p < 0.0001). The determinants of poor functional outcome at 3 months were the sex (RR 1.22 [1.01-1.48] for women, p = 0.0385) and the occurrence of onset symptom in rural landscape (RR 1.26 [1.03-1.55], p = 0.0219) compared to urban landscape. CONCLUSIONS: We provided an exhaustive overview and real-life professional practices conditions in thrombolyzed AIS. Despite a later prehospital management in neurovascular units and more severe strokes at admission, women and men had both similar outcomes at hospital discharge and in 3-month survival, but women were associated to worst functional outcome at 3 months.

Improving Access to Thrombolysis and Inhospital Management Times in Ischemic Stroke: A Stepped-Wedge Randomized Trial.

BACKGROUND AND PURPOSE: A suboptimal number of ischemic stroke patients eligible for thrombolysis actually receive it, partly because of extended inhospital delays. We developed a comprehensive program designed for emergency unit staff and evaluated its effectiveness for reducing intrahospital times and improving access to thrombolysis. METHODS: We conducted a randomized stepped-wedge controlled trial in 18 emergency unit. The sequentially implemented training intervention, targeting emergency physicians and nurses, was based on specifically designed videos and interactive simulation workshops on intrahospital management optimization. The effectiveness was assessed on intrahospital times and thrombolysis proportion. During the study period, all consecutive patients with confirmed ischemic stroke and no contraindications to thrombolysis were included. RESULTS: A total of 328 patients were enrolled in the control group and 363 in the intervention group. Mean age was 73.6 years. Overall thrombolysis proportion was 34.2% in the intervention group versus 25.6% in the control group (adjusted odds ratio, 1.42; 95% confidence interval, 1.01-2.01), thrombolysis proportion within 4 hours 30 minutes almost doubled (adjusted odds ratio, 1.9; 95% confidence interval, 1.32-2.73). Although imaging-to-stroke unit time was significantly decreased in the intervention group (39 versus 53 minutes; P=0.03), median door-to-imaging and door-to-needle times were not different between groups (P=0.70 and P=0.40, respectively). CONCLUSIONS: An interactive and multifaceted training program targeting emergency professionals was significantly associated with an increased access to thrombolysis, especially within 4 hours and 30 minutes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02814760.

Secondary Prevention Three and Six Years after Stroke Using the French National Insurance Healthcare System Database.

BACKGROUND: Secondary prevention is inadequate in the first 2 years after stroke but what happens after that is less documented. The aim of this study was to assess the use and the adherence to preventive drugs 3 and 6 years after experiencing a transient ischemic attack (TIA) or an ischemic stroke (IS). METHODS: The population study was from the AVC69 cohort (IS or TIA admitted in an emergency or stroke unit in the Rhône area, France, for an IS or a TIA during a 7-month period). Medication use was defined as ≥1 purchase during the studied year and adherence as Continuous Measure of Medication Acquisition ≥0.8 using the French medical insurance health care funding database. RESULTS: The study population consisted of 210 patients at 3 years and 163 patients at 6 years. Medication use at 3 and 6 years was, respectively, 80.9 and 79.8% for antithrombotics, 69.1 and 66.3% for antihypertensives, 60.5 and 55.2% for statins and 48.6 and 46.6% for optimal treatment defined as the treatment achieved by the use of the 3 drugs. Adherence to each class was good at 3 years and tends to decrease at 6 years. CONCLUSIONS: More than one patient out of 2 do not use the optimal preventive treatment.