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.

What are the available online resources targeting psychosocial burden among stroke survivors and their informal caregivers: A scoping review.

Background: After discharge home, stroke survivors and their informal caregivers face a significant lack of support and information which accentuates their psychosocial burden. Online resources might provide this support and address psychosocial needs, but existing online stroke programmes mainly target functional rehabilitation. We aimed to map the existing literature on online resources that have been evaluated in stroke rehabilitation and aimed at reducing psychosocial impact in stroke survivors and informal caregivers. Methods: MEDLINE was searched (2010-2024) to identify studies investigating online resources targeting psychosocial health. Studies were selected and extracted independently by two reviewers. We described the content, use, and psychosocial impact of these interventions using a narrative approach. Results: Eleven studies were included in the review, reporting 10 online resources (two studies relating to the same resource). Online resources were heterogeneous: eight information/resources websites, one mobile app, and one forum. Five online resources were dedicated to stroke survivors, four to stroke survivors and their informal caregivers, and one to informal caregivers. Two randomized controlled trials reported a significant decrease in depressive symptoms associated with the use of online resources. Stroke survivors and informal caregivers find online resources useful and acceptable to address their psychosocial needs. Conclusions: Few online stroke resources have been designed and evaluated to support post-stroke psychosocial rehabilitation. Further larger-scale research needs to study the impact of these interventions on psychosocial recovery over time.

Vascular hyperintensities on baseline FLAIR images are associated with functional outcome in stroke patients with successful recanalization after mechanical thrombectomy.

PURPOSE: The purpose of this study was to assess the prognostic value of vascular hyperintensities on FLAIR images (VHF) at admission MRI in patients with acute ischemic stroke (AIS) achieving successful recanalization after mechanical thrombectomy. MATERIALS AND METHODS: Patients with AIS treated by mechanical thrombectomy following admission MRI from the single-center HIBISCUS-STROKE cohort were assessed for eligibility. VHF were categorized using a four-scale classification and were considered poor when grade < 3 (i.e., absence of distal VHF). Recanalization was considered successful when modified thrombolysis in cerebral infarction score was ≥ 2B Functional outcome was considered poor if modified Rankin scale (mRS) at three months was > 2. Univariable and multiple variable logistic regressions were performed to identify factors associated with poor functional outcome despite successful recanalization. RESULTS: A total of 108 patients were included. There were 65 men and 43 women with a median age of 70.5 years (interquartile range: 55.0, 81.0; age range: 22.0-93.0 years). Among them, 39 subjects (36.1%) had poor functional outcome at three months. Univariable logistic regressions indicated that poorly extended VHF (VHF grade < 3) were associated with a poor functional outcome (P = 0.008) as well as age, hypertension and diabetes, baseline National Institute of Health Stroke Scale (NIHSS) score, pre-stroke mRS, lack of intravenous thrombolysis, cerebral microangiopathy and the presence of microbleeds. Multivariable analysis confirmed that poor VHF status was independently associated with a poor functional outcome (odds ratio [OR], 4.26; 95% confidence interval [CI]: 1.55-12.99; P = 0.007) in combination with hypertension (OR, 1.25; 95% CI: 0.87-1.85; P = 0.02), baseline NIHSS score (OR, 1.09; 95% CI: 1.04-1.20; P = 0.03), pre-stroke mRS (OR, 2.05; 95% CI: 1.07-4.61; P = 0.05) and lack of intravenous thrombolysis (OR, 0.23; 95% CI: 0.08-0.61; P = 0.004). CONCLUSION: Poorly extended VHF (grade <3) at admission MRI are associated with a poor functional outcome at three months despite successful recanalization by mechanical thrombectomy.

Blood-Brain Barrier Permeability and Kinetics of Inflammatory Markers in Acute Stroke Patients Treated With Thrombectomy.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the relationship between baseline blood-brain barrier (BBB) permeability and the kinetics of circulating inflammatory markers in a cohort of acute ischemic stroke (AIS) patients treated with mechanical thrombectomy. METHODS: The CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke includes AIS patients treated with mechanical thrombectomy after admission MRI and undergoing a sequential assessment of circulating inflammatory markers. Baseline dynamic susceptibility perfusion MRI was postprocessed with arrival time correction to provide K2 maps reflecting BBB permeability. After coregistration of apparent diffusion coefficient and K2 maps, the 90th percentile of K2 value was extracted within baseline ischemic core and expressed as a percentage change compared with contralateral normal-appearing white matter. Population was dichotomized according to the median K2 value. Univariable and multiple variable logistic regression analyses were performed to investigate factors associated with increased pretreatment BBB permeability in the whole population and in patients with symptom onset <6 hours. RESULTS: In the whole population (n = 105 patients, median K2 = 1.59), patients with an increased BBB permeability had higher serum levels of matrix metalloproteinase (MMP)-9 at H48 (p = 0.02), a higher C-reactive protein (CRP) serum level at H48 (p = 0.01), poorer collateral status (p = 0.01), and a larger baseline ischemic core (p < 0.001). They were more likely to have hemorrhagic transformation (p = 0.008), larger final lesion volume (p = 0.02), and worst neurologic outcome at 3 months (p = 0.04). The multiple variable logistic regression indicated that an increased BBB permeability was associated only with ischemic core volume (odds ratio [OR] 1.04, 95% CI 1.01-1.06, p < 0.0001). Restricting analysis to patients with symptom onset <6 hours (n = 72, median K2 = 1.27), participants with an increased BBB permeability had higher serum levels of MMP-9 at H0 (p = 0.005), H6 (p = 0.004), H24 (p = 0.02), and H48 (p = 0.01), higher CRP levels at H48 (p = 0.02), and a larger baseline ischemic core (p < 0.0001). The multiple variable logistic analysis showed that increased BBB permeability was independently associated with higher H0 MMP-9 levels (OR 1.33, 95% CI 1.12-1.65, p = 0.01) and a larger ischemic core (OR 1.27, 95% CI 1.08-1.59, p = 0.04). DISCUSSION: In AIS patients, increased BBB permeability is associated with a larger ischemic core. In the subgroup of patients with symptom onset <6 hours, increased BBB permeability is independently associated with higher H0 MMP-9 levels and a larger ischemic core.

C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease with highly variable clinical presentation and outcomes. Clinical studies suggest a role of inflammation and coagulation in CVST outcomes. The aim of this study was to investigate the association of inflammation and hypercoagulability biomarkers with CVST clinical manifestations and prognosis. Methods: This prospective multicenter study was conducted from July 2011 to September 2016. Consecutive patients referred to 21 French stroke units and who had a diagnosis of symptomatic CVST were included. High-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), D-dimer, and thrombin generation using calibrated automated thrombogram system were measured at different time points until 1 month after anticoagulant therapy discontinuation. Results: Two hundred thirty-one patients were included. Eight patients died, of whom 5 during hospitalization. The day 0 hs-CRP levels, NLR, and D-dimer were higher in patients with initial consciousness disturbance than in those without (hs-CRP: 10.2 mg/L [3.6-25.5] vs 23.7 mg/L [4.8-60.0], respectively; NLR: 3.51 [2.15-5.88] vs 4.78 [3.10-9.59], respectively; D-dimer: 950 µg/L [520-2075] vs 1220 µg/L [950-2445], respectively). Patients with ischemic parenchymal lesions (n = 31) had a higher endogenous thrombin potential5pM than those with hemorrhagic parenchymal lesions (n = 31): 2025 nM min (1646-2441) vs 1629 nM min (1371-2090), respectively (P = .0082). Using unadjusted logistic regression with values >75th percentile, day 0 hs-CRP levels of >29.7 mg/L (odds ratio, 10.76 [1.55-140.4]; P = .037) and day 5 D-dimer levels of >1060 mg/L (odds ratio, 14.63 [2.28-179.9]; P = .010) were associated with death occurrence. Conclusion: Two widely available biomarkers measured upon admission, especially hs-CRP, could help predict bad prognosis in CVST in addition to patient characteristics. These results need to be validated in other cohorts.

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.

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.

Assessment of three MR perfusion software packages in predicting final infarct volume after mechanical thrombectomy.

AIMS: To evaluate the performance of three MR perfusion software packages (A: RAPID; B: OleaSphere; and C: Philips) in predicting final infarct volume (FIV). METHODS: This cohort study included patients treated with mechanical thrombectomy following an admission MRI and undergoing a follow-up MRI. Admission MRIs were post-processed by three packages to quantify ischemic core and perfusion deficit volume (PDV). Automatic package outputs (uncorrected volumes) were collected and corrected by an expert. Successful revascularization was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2B. Uncorrected and corrected volumes were compared between each package and with FIV according to mTICI score. RESULTS: Ninety-four patients were included, of whom 67 (71.28%) had a mTICI score ≥2B. In patients with successful revascularization, ischemic core volumes did not differ significantly from FIV regardless of the package used for uncorrected and corrected volumes (p>0.15). Conversely, assessment of PDV showed significant differences for uncorrected volumes. In patients with unsuccessful revascularization, the uncorrected PDV of packages A (median absolute difference -40.9 mL) and B (median absolute difference -67.0 mL) overestimated FIV to a lesser degree than package C (median absolute difference -118.7 mL; p=0.03 and p=0.12, respectively). After correction, PDV did not differ significantly from FIV for all three packages (p≥0.99). CONCLUSIONS: Automated MRI perfusion software packages estimate FIV with high variability in measurement despite using the same dataset. This highlights the need for routine expert evaluation and correction of automated package output data for appropriate patient management.

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.

Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: The incidence of early seizures (occurring within 7 days of stroke onset) after intracerebral haemorrhage reaches 30% when subclinical seizures are diagnosed by continuous EEG. Early seizures might be associated with haematoma expansion and worse neurological outcomes. Current guidelines do not recommend prophylactic antiseizure treatment in this setting. We aimed to assess whether prophylactic levetiracetam would reduce the risk of acute seizures in patients with intracerebral haemorrhage. METHODS: The double-blind, randomised, placebo-controlled, phase 3 PEACH trial was conducted at three stroke units in France. Patients (aged 18 years or older) who presented with a non-traumatic intracerebral haemorrhage within 24 h after onset were randomly assigned (1:1) to levetiracetam (intravenous 500 mg every 12 h) or matching placebo. Randomisation was done with a web-based system and stratified by centre and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Treatment was continued for 6 weeks. Continuous EEG was started within 24 h after inclusion and recorded over 48 h. The primary endpoint was the occurrence of at least one clinical seizure within 72 h of inclusion or at least one electrographic seizure recorded on continuous EEG, analysed in the modified intention-to-treat population, which comprised all patients who were randomly assigned to treatment and who had a continuous EEG performed. This trial was registered at ClinicalTrials.gov, NCT02631759, and is now closed. Recruitment was prematurely stopped after 48% of the recruitment target was reached due to a low recruitment rate and cessation of funding. FINDINGS: Between June 1, 2017, and April 14, 2020, 50 patients with mild-to-moderate severity intracerebral haemorrhage were included: 24 were assigned to levetiracetam and 26 to placebo. During the first 72 h, a clinical or electrographic seizure was observed in three (16%) of 19 patients in the levetiracetam group versus ten (43%) of 23 patients in the placebo group (odds ratio 0·16, 95% CI 0·03-0·94, p=0·043). All seizures in the first 72 h were electrographic seizures only. No difference in depression or anxiety reporting was observed between the groups at 1 month or 3 months. Depression was recorded in three (13%) patients who received levetiracetam versus four (15%) patients who received placebo, and anxiety was reported for two (8%) patients versus one (4%) patient. The most common treatment-emergent adverse events in the levetiracetam group versus the placebo group were headache (nine [39%] vs six [24%]), pain (three [13%] vs ten [40%]), and falls (seven [30%] vs four [16%]). The most frequent serious adverse events were neurological deterioration due to the intracerebral haemorrhage (one [4%] vs four [16%]) and severe pneumonia (two [9%] vs two [8%]). No treatment-related death was reported in either group. INTERPRETATION: Levetiracetam might be effective in preventing acute seizures in intracerebral haemorrhage. Larger studies are needed to determine whether seizure prophylaxis improves functional outcome in patients with intracerebral haemorrhage. FUNDING: French Ministry of Health.

Inflammatory profile and white matter hyperintensity burden in acute ischemic stroke patients.

Inflammation is involved in small vessel disease (SVD). We aim to clarify whether inflammation related to white matter hyperintensities (WMH), a key component of SVD, may affect the inflammatory response in acute ischemic stroke (AIS) patients. For this, we sequentially measured 10 circulating inflammatory markers and assessed WMH burden on admission MRI in AIS patients treated with thrombectomy. Of 149 patients, 57 (38.3%) had a high WMH burden (Fazekas≥3). A high WMH burden was associated with 4 markers levels but this association did not remain following multivariable analyses. WMH burden is not associated with a specific inflammatory profile in AIS.

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.

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.

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.

Does the Brush-Sign Reflect Collateral Status and DWI-ASPECTS in Large Vessel Occlusion?

Introduction: The relevance of the brush-sign remained poorly documented in large vessel occlusion (LVO). We aimed to assess the relationship between the brush-sign and collateral status and its potential impact on baseline diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) in acute ischemic stroke (AIS) patients eligible to mechanical thrombectomy (MT). Methods: Consecutive patients admitted in the Lyon Stroke Center with anterior circulation AIS due to intracranial internal carotid artery (ICA) and/or M1 or M2 segment of the middle cerebral artery (MCA) occlusion eligible for MT were included. The brush-sign was assessed on T2-gradient-echo MRI. Collateral status was assessed on digital subtraction angiography according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) score. Results: In this study, 504 patients were included, among which 171 (33.9%) patients had a brush-sign. Patients with a brush-sign more frequently had a poor collateral status [72 (42.1%) vs. 103 (30.9%); p = 0.017]. In univariable analysis, a DWI-ASPECTS < 7 was associated with a brush sign. Following multivariable analysis, the brush-sign no longer affected DWI-ASPECTS < 7 while the latter remained associated with younger age [odds ratio (OR) 0.97, 95% CI.96-0.99], male sex (OR 1.79, 95% CI 1.08-2.99), a higher National Institutes of Health Stroke Scale (NIHSS) score (OR 1.16, 95% CI 1.1-1.21), a poor collateral status (OR 9.35, 95% CI 5.59-16.02), MCA segment (OR 2.54, 95% CI 1.25-5.38), and intracranial ICA (OR 3.01, 95% CI 1.16-8) occlusion. Conclusions and Relevance: The brush-sign may be a marker of poor collateral status but did not independently predict a lower DWI-ASPECTS. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04620642.

Temporal trends in reperfusion therapy for patients with acute ischemic stroke.

OBJECTIVES: To analyze the temporal trends in thrombolysis rates after implementation of a regional emergency network for acute ischemic stroke (AIS). METHODS: We conducted a retrospective study based on a prospective multicenter observational registry. The AIS benefited from reperfusion therapy included in 1 of the 5 primary stroke units or 1 comprehensive stroke center and 37 emergency departments were included using a standardized case report form. The population covers 3 million inhabitants. RESULTS: In total, 32,319 AIS was reported in the regional hospitalization database of which 2215 thrombolyzed AIS patients were included in the registry and enrolled in this study. The annual incidence rate of thrombolysis continuously and significantly increased from 2010 to 2018 (10.2% to 17.3%, P-trend = 0.0013). The follow-up of the onset-to-door and the door-to-needle delays over the study period showed stable rates, as did the all-cause mortality rate at 3-months (13.2%). CONCLUSION: Although access to stroke thrombolysis has increased linearly since 2010, the 3-month functional outcome has not evolved as favorably. Further efforts must focus on reducing hospital delays.

Multiprofessional intervention to improve adherence to medication in stroke patients: a study protocol for a randomised controlled trial (ADMED AVC study).

INTRODUCTION: Adherence to secondary preventive medications is often suboptimal in patients with stroke, exposing them to an increased risk of recurrent cerebral and/or cardiovascular events. Effective actions in the long term to improve adherence to medication are needed. The study will evaluate the efficacy of a collaborative multiprofessional patient-centred intervention conducted by a pharmacist on adherence to secondary preventive medication in stroke survivors. METHODS AND ANALYSIS: This is a multicentre cluster-randomised controlled trial. Two groups of 91 patients (intervention vs standard care) will be recruited. The clinical pharmacist intervention targeting secondary preventive medication will consist of three parts over 1 year: (1) an individual semi-structured interview at hospital discharge; (2) follow-up telephone interviews at 3, 6 and 9 months after discharge; and (3) a final individual semi-structured interview 1 year after discharge. Information on patient follow-up will be shared with the general practitioner and the community pharmacist by sending a report of each interview. The primary outcome is adherence to medication during the 12 months after hospital discharge, assessed using a composite endpoint: the medication possession ratio associated with a self-administered questionnaire. ETHICS AND DISSEMINATION: The local ethics committee, the national committee for use of personal data in medical research and the national data protection agency approved the study. The sponsor has no role in study design; collection, analysis and interpretation of data; or report writing. DISCUSSION: This pharmacist-led educational programme has the potential to significantly improve adherence to medication in stroke survivors which could lead to a decrease in recurrent cerebral and/or cardiovascular events. TRIAL REGISTRATION NUMBER: NCT02611440.

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.

A lower admission level of interleukin-6 is associated with first-pass effect in ischemic stroke patients.

BACKGROUND: First-pass effect (FPE) defined as a complete or near-complete reperfusion achieved after a single thrombectomy pass is predictive of favorable outcome in acute ischemic stroke (AIS) patients. We aimed to assess whether admission levels of inflammatory markers are associated with FPE. METHODS: HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) includes AIS patients with large vessel occlusion treated with mechanical thrombectomy following brain MRI. C-reactive protein, interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, soluble tumor necrosis factor receptor I, soluble form suppression of tumorigenicity 2, matrix metalloproteinase-9 (MMP-9), soluble P-selectin, and vascular cellular adhesion molecule-1 were measured in admission sera using an ELISA assay. FPE was defined as a complete or near-complete reperfusion (thrombolysis in cerebral infarction scale (TICI) 2c or 3) after the first pass. A multivariate logistic regression analysis was performed to assess independent factors associated with FPE. RESULTS: A total of 151 patients were included. Among them, 43 (28.5%) patients had FPE. FPE was associated with low admission levels of IL-6, MMP-9, and platelet count, an older age, lack of hypertension, lack of tandem occlusion, a shorter thrombus length, and a reduced procedural time. Following multivariate analysis, a low admission level of IL-6 was associated with FPE (OR 0.66, 95% CI 0.46 to 0.94). Optimal cut-off of IL-6 level for distinguishing FPE from non-FPE was 3.0 pg/mL (sensitivity 92.3%, specificity 42.3%). CONCLUSION: A lower admission level of IL-6 is associated with FPE.

Cerebral Venous Thrombosis: Clinical, Radiological, Biological, and Etiological Characteristics of a French Prospective Cohort (FPCCVT)-Comparison With ISCVT Cohort.

Introduction: Cerebral venous thrombosis (CVT) is a rare disease with highly variable clinical presentation and outcome. Etiological assessment may be negative. The clinical and radiological presentation and evolution can be highly variable. The mechanisms involved in this variability remain unknown. Objective: The aim of this multicenter French study registered on ClinicalTrials.gov (NCT02013635) was therefore to prospectively recruit a cohort of patients with cerebral venous thrombosis (FPCCVT) in order to study thrombin generation and clot degradation, and to evaluate their influence on clinical radiological characteristics. The first part of the study was to compare our cohort with a reference cohort. Methods: This prospective, multicenter, French study was conducted from July 2011 to September 2016. Consecutive patients (aged >15 years) referred to the stroke units of 21 French centers and who had a diagnosis of symptomatic CVT were included. All patients gave their written informed consent. The diagnosis of CVT had to be confirmed by imaging. Clinical, radiological, biological, and etiological characteristics were recorded at baseline, at acute phase, at 3 months and at last follow-up visit. Thrombophilia screening and the choice of treatment were performed by the attending physician. All data were compared with data from the International Study on CVT published by Ferro et al. Results: Two hundred thirty-one patients were included: 117 (50.6%) had isolated intracranial hypertension, 96 (41.5%) had focal syndrome. During hospitalization, 229 (99.1%) patients received anticoagulant treatment. Median length of hospital stay was 10 days. Five patients died during hospitalization (2.2%). At 3 months, 216 patients (97.0%) had follow-up with neurological data based on an outpatient visit. The mean duration of antithrombotic treatment was 9 months, and the mean time to last follow-up was 10.5 months. At the end of follow-up, eight patients had died, and 26 patients were lost to follow-up. At least one risk factor was identified in 200 patients. Conclusions: We demonstrated that the FPCCVT cohort had radiological, biological, and etiological characteristics similar to the historical ISCVT cohort. Nevertheless, the initial clinical presentation was less severe in our study probably due to an improvement in diagnostic methods between the two studies.