Medical demography at stroke centers: Current situation in France.

INTRODUCTION: Following the 2010-2014 French national stroke action plan, the number of stroke center (SC) has gradually increased in France, allowing a homogeneous coverage and access to neurovascular care in organized and territorially defined structures. However, operational difficulties within SCs have been progressively reported over the last few years. The objective of this study was to identify the medical staff shortages in SC that may contribute to these difficulties. METHODS: A survey on the medical staffing level as of January 1, 2021 was sent to all French SC managers. Specific questions related on vacancies, need of interim medical staff, and participation in out-of-hour healthcare services. RESULTS: Among the 139 SC managers contacted, 122 (88%) filled in the questionnaire. Analysis of the data showed that over 879 physician positions opened, 163 (18.5%) remained vacant for a mean of two years, and that in 51 SCs (41.9%), more than two positions were unfilled. In 13 of these 51 SCs, the out-of-hour healthcare services relied on less than four practitioners, defining a critical situation, and three other SCs had to close temporarily (2) or permanently (1). Moreover, 39.2% of SCs with at least one vacancy used interim physicians, for a median period of 12.5 weeks/year (IQR 5-18). CONCLUSION: This study highlights the significant medical staff shortage in French SCs. In the absence of urgent measures, more SCs will close, jeopardizing the regional network and access to care for stroke patients.

TICI-RANKIN mismatch: Poor clinical outcome despite complete endovascular reperfusion in the ETIS Registry.

INTRODUCTION: Endovascular treatment (EVT) is a well-established technic for acute ischemic stroke, but despite a high recanalization rate of near 80%, at 3 months roughly 50% of patients have a poor functional outcome with a modified Rankin score (mRS) ≥3. The aim of this study was to determine predictive factors of poor functional outcomes in patients with complete recanalization after EVT, defined as modified thrombolysis in cerebral infarction (mTICI) 3. PATIENTS AND METHODS: This retrospective analysis based on the prospective multicenter ETIS registry (endovascular treatment in ischemic stroke) in France included 795 patients from January 2015 and November 2019 with acute ischemic stroke due to anterior circulation occlusion and prestroke mRS 0-1, treated with EVT and who achieved complete recanalization. Univariate and multivariate logistic regression models were used to identify predictive factors of poor functional outcome. RESULTS: 365 patients (46%) showed a poor functional outcome (mRS>2). In backward-stepwise logistic regression analysis, poor functional outcome was independently associated with older age (OR per 10-year increase, 1.51; 95%CI, 1.30 to 1.75), higher admission NIHSS (OR per 1 point increase, 1.28; 95%CI, 1.21 to 1.34), absence of prior intravenous thrombolysis (OR, 0.59; 95%CI, 0.39 to 0.90), and an unfavorable 24-hour NIHSS change (24h-baseline) (OR, 0.82; 95%CI, 0.79 to 0.87). We calculated that patients whose 24h NIHSS decreased by less than 5 points are more at risk of a poor outcome, with a sensitivity and a specificity of 65.0%. CONCLUSION: Despite complete reperfusion after EVT, half of patients had a poor clinical outcome. These patients, who were mainly older with a high initial NIHSS and an unfavorable post-EVT 24h NIHSS change, could represent a target population for early neurorepair and neurorestorative strategies.

Tenecteplase in acute ischemic stroke: Review of the literature and expert consensus from the French Neurovascular Society.

BACKGROUND: Intravenous alteplase is the only thrombolytic treatment approved for patients with acute ischemic stroke (AIS). Although no randomized controlled trial (RCT) has shown the superiority of tenecteplase over alteplase in AIS, tenecteplase is increasingly used off-label in Stroke Units. The purpose of the present work was to provide an up-to-date set of expert consensus statements on the use of tenecteplase in AIS. METHODS: Members of the working group were selected by the French Neurovascular Society. RCTs comparing tenecteplase and alteplase in the treatment of AIS were reviewed. Recent meta-analysis and real-life experience data on tenecteplase published until 30th October 2021 were also analyzed. After a description of the available data, we tried to answer the subsequent questions about the use of tenecteplase in AIS: What dosage of tenecteplase should be preferred? How effective is tenecteplase for cerebral artery recanalization? What is the clinical effectiveness of tenecteplase? What is the therapeutic safety of tenecteplase? What are the benefits associated with tenecteplase ease of use? Then expert consensus statements for tenecteplase use were submitted. In October 2021 the working group was asked to review and revise the manuscript. In November 2021, the current version of the manuscript was approved. EXPERT CONSENSUS: A set of three expert consensus statements for the use of tenecteplase within 4.5hours of symptom onset in AIS patients were issued: (1) It is reasonable to use tenecteplase 0.25mg/kg when mechanical thrombectomy (MT) is planned. (2) Tenecteplase 0.25mg/kg can be used as an alternative to alteplase 0.9mg/kg in patients with medium- or small-vessel occlusion not retrievable with MT. (3) Tenecteplase 0.25mg/kg could be considered as an alternative to alteplase 0.9mg/kg in patients without vessel occlusion. CONCLUSIONS: These expert consensus statements could provide a framework to guide the clinical decision-making process for the use of tenecteplase according to admission characteristics of AIS patients. However, existing data are limited, requiring inclusions in ongoing RCTs or real-life registries.

Alert on elongated in-hospital acute stroke management delays. An Aquitain cohort study.

The objectives were to analyze changes from 2012 to 2017 in different management times of stroke patients included in the Aquitaine stroke Observatory (ObA2). The studied times (onset-to-needle time-ONT, onset-to-door time-ODT, door-to-imaging time-DIT, door-to-needle time-DNT and imaging-to-needle time-INT) were described as median, interquartile ranges and proportion of patients within the recommended median time goals (ODT under 4hours, DIT within 20min; for thrombolyzed patients, DIT under 20min and a ONT under 4:30) to be compared with an objective of 50% of patients within said time goal. Globally, ODT was 160min, with 43.6% to 59.6% of patients within the ODT goal along the study period. With no improvement over time, the proportion of patients within the DIT goal stayed stable and at a low level (range: 5.5-7.0%) for all patients, decreasing from 25.2% to 11.4% for thrombolyzed patients. The proportion of thrombolyzed patients within the DNT goal varied from 15.1% to 30.3% during study period. These results highlight the urgent need for action to improve in-hospital management of stroke patients, focusing on delays between admission and imaging.

General anesthesia or conscious sedation for endovascular therapy of basilar artery occlusions: ETIS registry results.

BACKGROUND AND PURPOSE: Acute basilar artery occlusions (BAO) are associated with poor outcome despite modern endovascular treatment (EVT). The best anesthetic management during EVT is not known and may affect the procedure and clinical outcome. We compared the efficacy and safety of general anesthesia (GA) and conscious sedation/local anesthesia (CS/LA) in a large cohort of stroke patients with BAO treated with EVT in current clinical practice. METHODS: Data from the ongoing prospective multicenter Endovascular Treatment In Ischemic Stroke Registry of consecutive acute BAO patients who had EVT indication from January 1st, 2015, to December 31st, 2021, were retrospectively analyzed. Two groups were compared: patients treated with CS/LA versus GA (both types of anesthesia being performed in the angiosuite). Good outcome was defined as modified Rankin Scale (mRS) score 0-3 at 90 days. RESULTS: Among the 524 included patients, 266 had GA and 246 had CS/LA (67 LA). Fifty-three patients finally did not undergo EVT: 15 patients (5.9%) in the GA group and 38 patients (16.1%) in the CS/LA group (P < 0.001). After matching, two groups of 129 patients each were retained for primary analysis. The two groups were well balanced in terms of baseline characteristics. After adjustment, CS/LA compared to GA was not associated with good outcome (OR=0.90 [95%CI 0.46-1.77] P=0.769) or mortality (OR=0.75 [0.37-1.49] P=0.420) or modified thrombolysis in cerebral infarction score 2b-3 (OR=0.43 [0.16-1.16] P=0.098). On mixed ordinal logistic regression, the modality of anesthesia was not associated with any significant change in the overall distribution of the 90-day mRS (adjusted OR=1.08 [0.62-1.88] P=0.767). CONCLUSIONS: Safety, outcome and quality of EVT under either CS/LA or GA for stroke due to acute BAO appear similar. Further randomized trials are warranted.

Safety and Efficacy of Cangrelor in Acute Stroke Treated with Mechanical Thrombectomy: Endovascular Treatment of Ischemic Stroke Registry and Meta-analysis.

BACKGROUND AND PURPOSE: Rescue therapies are increasingly used in the setting of endovascular therapy for large-vessel occlusion strokes. Among these, cangrelor, a new P2Y12 inhibitor, offers promising pharmacologic properties to join the reperfusion strategies in acute stroke. We assessed the safety and efficacy profiles of cangrelor combined with endovascular therapy in patients with large-vessel-occlusion stroke. MATERIALS AND METHODS: We performed a retrospective patient data analysis in the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France from July 2018 to December 2020 and conducted a systematic review and meta-analysis using several data bases. Indications for cangrelor administration were rescue strategy in case of refractory intracranial occlusion with or without intracranial rescue stent placement, and cervical carotid artery stent placement in case of cervical occlusion (tandem occlusion or isolated cervical carotid occlusion). RESULTS: In the clinical registry, 44 patients were included (median initial NIHSS score, 12; prior intravenous thrombolysis, 29.5%). Intracranial stent placement was performed in 54.5% (n = 24/44), and cervical stent placement, in 27.3% (n = 12/44). Adjunctive aspirin and heparin were administered in 75% (n = 33/44) and 40.9% (n = 18/44), respectively. Rates of symptomatic intracerebral hemorrhage, parenchymal hematoma, and 90-day mortality were 9.5% (n = 4/42), 9.5% (n = 4/42), and 24.4% (n = 10/41). Favorable outcome (90-day mRS, 0-2) was reached in 51.2% (n = 21/41), and successful reperfusion, in 90.9% (n = 40/44). The literature search identified 6 studies involving a total of 171 subjects. In the meta-analysis, including our series data, symptomatic intracerebral hemorrhage occurred in 8.6% of patients (95% CI, 5.0%-14.3%) and favorable outcome was reached in 47.6% of patients (95% CI, 27.4%-68.7%). The 90-day mortality rate was 22.6% (95% CI, 13.6%-35.2%). Day 1 artery patency was observed in 89.7% (95% CI, 81.4%-94.6%). CONCLUSIONS: Cangrelor offers promising safety and efficacy profiles, especially considering the complex endovascular reperfusion procedures in which it is usually applied. Further large prospective data are required to confirm these findings.

High glycemic variability: An underestimated determinant of stroke functional outcome following large vessel occlusion.

BACKGROUND AND PURPOSE: Early glycemic variability (GV) in diabetic patients is a poor prognosis factor following cardiovascular events. However, its influence on the course of acute ischemic stroke (AIS) with large vessel occlusion remains unclear. We investigated the relationship between high GV during acute stroke and three-month functional outcome among patients treated with combined intravenous thrombolysis and endovascular therapy for large vessel occlusion. METHODS: A single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent thrombolysis and mechanical thrombectomy between January 2015 and May 2017. Early GV was assessed using standard deviation (SD) of blood glucose levels for the first 24hours. The main outcome was functional status at three months as defined by the modified Rankin scale (mRS). Secondary outcomes were change in NIHSS score from baseline to 24hours and occurrence of severe hemorrhagic transformation. Multivariate logistic regression analyses including GV, admission glycemia and mean glycemia were performed. RESULTS: Among the 93 patients evaluated, 26 had early high GV (≥20.9mg/dl). High GV was associated with poor functional outcome (OR=8.00; 95%CI [1.34-47.89]; P=0.02) unlike admission glycemia and mean glycemia (OR=2.92; 95%CI [0.51-16.60]; P=0.23 and OR=0.36; 95%CI [0.05-2.6]; p=0.31, respectively). High GV was not associated with NIHSS at 24hours or hemorrhagic transformation. CONCLUSION: Acute high GV contributes to poorer functional outcome following AIS related to large vessel occlusion and should be considered as a new target in acute stroke management.

Management of stroke in patients on antithrombotic therapy: Practical issues in the era of direct oral anticoagulants.

Antithrombotic drugs (ADs) are the mainstay of secondary prevention of thrombotic vascular diseases. Management of patients under long-term treatment with ADs admitted for acute cerebrovascular disease, either ischemic stroke (IS) or intracerebral hemorrhage (ICH), has become a frequent situation that might influence decision-making processes from diagnosis to therapeutic strategies. The aim of this review is to summarize current data from the literature to help clinicians in their decisions for stroke care in patients taking ADs. While a large body of data have made it possible to codify the management of patients presenting IS or ICH under antiplatelet drugs and vitamin K antagonists, the increasing use of direct oral anticoagulants (DOAs) and future development of new antiplatelet drugs raise new problems. Development of rapid assessment tools measuring specific biological activity and reversion agents dedicated to each class of DOAs should make it possible to optimize individual therapeutic strategies. This review highlights the main steps of IS and ICH management from early identification of ADs, and use of dedicated biological assays, to the stepwise strategy to apply revascularization or reversal therapies and finally the resumption of ADs with a focus on individual clinical and radiological characteristics for more personalized care.

Depression and routinization following stroke.

OBJECTIVE: Post-stroke depression is a frequent complication of stroke that has detrimental consequences for quality of life and functional outcomes. Daily life routines may increase feelings of security for some individuals confronted with age-related health concerns, but little information is available concerning their role following stroke. The aim of this investigation was to examine the association of depression and other psychological variables at hospitalization for stroke and behavioral routines and mood symptoms three months later using Ecological Momentary Assessment (EMA). METHODS: Forty-four patients with minor ischemic stroke were consecutively enrolled in the study. Stroke severity, handicap, depression and anxiety symptoms were assessed at baseline. EMA data acquired three months later were coded for the repetition of specific activities or behaviors occurring within the same time period across days. RESULTS: Higher baseline depression and anxiety symptom severity were significantly associated with increased behavioral routines three months after stroke. The occurrence of routines was associated with a higher level of depressive symptomatology over subsequent hours of the day. CONCLUSION: The findings demonstrate a general correlation between baseline psychological vulnerability and routines three months later, but within-day analyses suggest that routines may increase the risk of negative affect in this vulnerable population.

A Multicenter Preliminary Study of Cangrelor following Thrombectomy Failure for Refractory Proximal Intracranial Occlusions.

BACKGROUND AND PURPOSE: Rescue endovascular and pharmacologic approaches are increasingly being adopted after recanalization failure of acute large-vessel occlusion strokes with mechanical thrombectomy, with encouraging results. The safety and efficacy of glycoprotein IIb/IIIa inhibitors in ischemic stroke have been investigated, though cangrelor, a recent intravenous P2Y12-receptor inhibitor with a rapid onset/offset of action and a short half-life, may be a valuable option. We compared the safety and efficacy of cangrelor with those of glycoprotein IIb/IIIa inhibitors for refractory occlusions. MATERIALS AND METHODS: We performed a retrospective analysis of the ongoing prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke Registry in France between May 2012 and February 2020. Refractory intracranial occlusions of the anterior and posterior circulation were included and defined as recanalization failure of large-vessel occlusion stroke, perioperative target artery reocclusion, or high risk of early reocclusion related to an arterial wall lesion. The primary end point was a favorable outcome, defined as a 90-day mRS of 0-2. Secondary end points were reperfusion, intracranial hemorrhage, and procedural complications. RESULTS: Among 69 patients, 15 were treated with cangrelor, and 54, with glycoprotein IIb/IIIa inhibitors. The favorable outcome (adjusted OR = 2.22; 95% CI, 0.42-11.75; P = .348) and mortality (adjusted OR = 0.44; 95% CI, 0.06-3.16; P = .411) rates were similar in both groups. There was no difference in the rates of any intracranial hemorrhage (adjusted OR = 0.40; 95% CI, 0.08-2.09; P = .280), symptomatic intracranial hemorrhage (6.7% versus 0.0%, P = .058), or procedural complications (6.7% versus 20.4%, P = .215). Reperfusion rates were higher in the cangrelor group, though the difference did not reach statistical significance (93.3% versus 75.0% for modified TICI 2b-3; adjusted OR =10.88; 95% CI, 0.96-123.84; P = .054). CONCLUSIONS: Cangrelor seems to be as safe as glycoprotein IIb/IIIa inhibitors for managing refractory intracranial occlusion and leads to satisfactory brain reperfusion. Cangrelor is a promising agent in this setting, and additional studies are warranted to confirm our findings.

Is addictive-like eating an overlooked stroke risk factor? A study case.

PURPOSE: While stroke is already considered a nutrition-related disease, the prevalence of the broad array of disordered eating behaviors is under-reported in this disease. We describe the case of a stroke in a young woman following a recent food addiction to fatty-sweet food. METHODS: She was diagnosed with a Night-Eating-Syndrome, with a loss-of-control exclusively towards sugary carbohydrates used to manage her insomnia and distress, and her consummatory behaviors were investigated. RESULTS: This case report illustrates a self-medication of a significant psychological distress by shifting from a healthy diet to an overconsumption of hyper-palatable foods, triggering an addiction disorder. The related hypertriglyceridemia, on top of chronic smoking, contributed to the development of an atherosclerotic plaque and thrombus formation. CONCLUSION: Food addiction might be considered as an emerging stroke risk factor. We suggest it fosters the need to take into consideration addictive-like eating behaviors and associated mental disorders in the primary and secondary prevention of stroke. This may be particularly relevant for the prevention of stroke in women as they are more prone to comfort their emotions with food. LEVEL OF EVIDENCE: V, descriptive study.

Influence of inflammatory status in the acute phase of stroke on post-stroke depression.

BACKGROUND: Thirty percent of stroke patients will suffer from post-stroke depression (PSD). Recent data suggest that inflammation accounts for a substantial amount of depression. Our primary objective was to assess the association between standard inflammation biomarkers in the acute phase of stroke and PSD at three months. The secondary objective was to elaborate a predictive model of PSD from clinical, biological and radiological data. METHODS: We performed a retrospective analysis of a single-centre cohort of stroke patients with a three-month follow-up. Serum levels of C-reactive protein (CRP), fibrinogen, leukocyte count and neutrophil to lymphocyte ratio (NLR) were tested at admission and at peak. Mood was assessed at three months using the depression sub-scale of the Hospital Anxiety and Depression Scale (HADS). Association between inflammation biomarkers and HADS was evaluated with multi-linear regression adjusted on clinical and radiological parameters. Logistic predictive models of PSD at three months, with and without inflammation biomarkers, were compared. RESULTS: Three hundred and forty-eight patients were included, of whom 20.06% developed PSD. Baseline and peak values of all inflammatory markers were associated with the severity of PSD at three months. Area under the curve for the receiver operating characteristic curve of PSD prediction was 0.746 (CI 95% 0.592-0.803) with selected inflammation biomarkers and 0.744 (CI 95% 0.587-0.799) without. CONCLUSION: Most inflammation biomarkers are weakly associated with PSD, adding negligible value to predictive models. While they suggest the implication of inflammation in PSD pathogenesis, they are useless for the prediction of PSD, underscoring the need for more specific biomarkers.

Acute Ischemic Stroke or Epileptic Seizure? Yield of CT Perfusion in a "Code Stroke" Situation.

BACKGROUND AND PURPOSE: The clinical differentiation between acute ischemic stroke and epileptic seizure may be challenging, and making the correct diagnosis could avoid unnecessary reperfusion therapy. We examined the accuracy of CTP in discriminating epileptic seizures from acute ischemic stroke without identified arterial occlusion. MATERIALS AND METHODS: We retrospectively identified consecutive patients in our emergency department who underwent CTP in the 4.5 hours following the development of an acute focal neurologic deficit who were discharged with a final diagnosis of acute ischemic stroke or epileptic seizure. RESULTS: Among 95 patients, the final diagnosis was epileptic seizure in 45 and acute ischemic stroke in 50. CTP findings were abnormal in 73% of the patients with epileptic seizure and 40% of those with acute ischemic stroke. Hyperperfusion was observed more frequently in the seizure group (36% versus 2% for acute ischemic stroke) with high specificity (98%) but low sensitivity (35%) for the diagnosis of epileptic seizure. Hypoperfusion was found in 38% of cases in each group and was not confined to a vascular territory in 24% of patients in the seizure group and 2% in the acute ischemic stroke group. The interobserver agreement was good (κ = 0.60) for hypo-, hyper-, and normoperfusion patterns and moderate (κ = 0.41) for the evaluation of vascular systematization. CONCLUSIONS: CTP patterns helped to differentiate acute ischemic stroke from epileptic seizure in a "code stroke" situation. Our results indicate that a hyperperfusion pattern, especially if not restricted to a vascular territory, may suggest reconsideration of intravenous thrombolysis therapy.

Prognosis and risk factors associated with asymptomatic intracranial hemorrhage after endovascular treatment of large vessel occlusion stroke: a prospective multicenter cohort study.

BACKGROUND AND PURPOSE: Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address its impact on 3-month functional outcome and to identify risk factors for aICH after EVT. METHODS: Patients with AIS attributable to anterior circulation large vessel occlusion who underwent EVT were enrolled in a multicenter prospective registry. Based on imaging performed 22-36 h post-EVT, we included patients with no intracranial hemorrhage (ICH) or aICH. Poor outcome defined as a 3-month modified Rankin Scale (mRS) score 4-6 and overall 3-month mRS score distribution were compared according to presence/absence of aICH, and aICH subtype using logistic regression. We assessed the risk factors of aICH using a multivariate logistic regression model. RESULTS: Of the 1526 patients included in the study, 653 (42.7%) had aICH. Patients with aICH had a higher rate of poor outcome: odds ratio (OR) 1.88 (95% confidence interval [CI] 1.44-2.44). Shift analysis of mRS score found a fully adjusted OR of 1.79 (95% CI 1.47-2.18). Hemorrhagic infarction (OR 1.63 [95% CI 1.22-2.18]) and parenchymal hematoma (OR 2.99 [95% CI 1.77-5.02]) were associated with higher risk of poor outcome. Male sex, diabetes, coronary artery disease, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, number of passes and onset to groin puncture time were independently associated with aICH. CONCLUSIONS: Patients with aICH, irrespective of the radiological pattern, have a worse functional outcome at 3 months compared with those without ICH after EVT for AIS. The number of EVT passes and the time from onset to groin puncture are factors that could be modified to reduce deleterious ICH.

Stroke care during the COVID-19 pandemic: experience from three large European countries.

In order to cope with the exponentially increasing number of patients infected with SARS-CoV-2, European countries made enormous efforts to reorganize medical assistance and several diseases, including stroke, were particularly impacted. We report the experience of stroke neurologists from three European countries (Italy, France and Germany) that faced the pandemic at diverse time points and with different approaches, depending on their resources and healthcare system organization. Pre-hospital and in-hospital acute stroke pathways were reorganized to prioritize COVID-19 management and, in severely affected regions of Italy and France, stroke care was centralized to a limited number of centers, whereas the remaining stroke units were dedicated to patients with COVID-19. Access to acute stroke diagnostics and time-dependent therapies was limited or delayed because of reduced capacities of emergency services due to the burden of patients with COVID-19. A marked reduction in the number of patients presenting with transient ischaemic attack and stroke was noted in the emergency departments of all three countries. Although we only have preliminary data, these conditions may have affected stroke outcome. These indirect effects of the COVID-19 pandemic could negate the efforts of stroke neurologists over the last few years to improve outcome and reduce mortality of stroke patients. Although the SARS-CoV-2 infection rate is slowing down in Europe, the effects of ending lockdown in the next months are unpredictable. It is important for the European and world stroke community to share what has been learned so far to be plan strategies to ensure stroke care in the future and upcoming challenging times.

Post-stroke pathway analysis and link with one year sequelae in a French cohort of stroke patients: the PAPASePA protocol study.

BACKGROUND: Stroke is a health problem with serious consequences, both in terms of mortality, and after-effects affecting patient quality of life. Stroke requires both urgent and chronic management involving the entire health care system. Although large variability in the management of stroke patients have been noticed, knowledge of the diversity and the scalability of post-stroke pathways, whether it is the care pathway or the life pathway, is currently not sufficient. Moreover the link between post-stroke pathways and patients sequelae have not been yet clearly defined. All this information would be useful to better target the needs to improve stroke patient management. The purposes are to identify the post-stroke life pathways components associated with sequelae (activity limitations - main purpose, cognitive disorders, anxio-depressive disorders, fatigue, participation restrictions) at 3 months and 1 year post-stroke, to define a typology of life pathways of patients during the post-stroke year and to analyze the social and geographical inequalities in the management of stroke. METHODS: Design: a prospective multicenter comparative cohort study with a follow up to 1 year after the acute episode. Participant centers: 13 hospitals in the Aquitaine region (France). STUDY POPULATION: patients diagnosed with a confirmed ischemic or hemorrhagic stroke included in the Aquitaine Observatory of Stroke (ObA2) cohort and voluntary to participate. Data sources are existing databases (ObA2 database and the French National Health Data System - SNDS) to collect information about care pathways, patient characteristics and stroke characteristics and Ad hoc surveys to collect information about life pathways and post-stroke sequelae. The endpoints of the study are post-stroke activity limitations evaluated by the modified Rankin score, other post-stroke sequelae (Cognitive disorders, anxio-depressive disorders, fatigue, restriction of participation) assessed by standardized and validated scales and Clusters of patients responding to pathways with common or similar characteristics.; DISCUSSION: By integrating a longitudinal dimension and relying on a large cohort, the project will make it possible to identify the sources of disturbances and the factors favorable to the outcome of the life pathways, important for the planning of the offer and the management of the public policies concerning stroke pathways. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03865173 , March 6th, 2019.

Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.

BACKGROUND: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]. CONCLUSIONS: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke.

Cost-effectiveness analysis of mechanical thrombectomy plus tissue-type plasminogen activator compared with tissue-type plasminogen activator alone for acute ischemic stroke in France.

BACKGROUND AND PURPOSE: Recent studies demonstrated the benefit of mechanical thrombectomy (MT) plus intravenous tissue-type plasminogen activator (IV-tPA) (MT-IV-tPA) in acute ischemic stroke. This study aimed to estimate the cost-utility of MT-IV-tPA compared with IV-tPA alone from the perspective of the French National Health Insurance. METHODS: We developed a decision tree for the first 3 months after stroke onset and a Markov model until 10 years post-stroke. The health states of the Markov model were according to the modified Rankin Scale (mRS): independent (mRS=0-2), dependent (mRS=3-5), dead (mRS=6). Recurrent stroke was the fourth health stage of our model. We conducted systematic literature reviews and meta-analyses to estimate the cost and utility of each health state, and the transition probabilities between health states. A microcosting study was conducted to estimate the cost of MT. We estimated the incremental cost-effectiveness ratio of MT-IV-tPA and conducted a probabilistic analysis in order to estimate the probability that MT-IV-tPA is cost-effective compared to IV-tPA, the expected value of perfect information (EVPI), and the expected value of partial perfect information (EVPPI), given the uncertainty surrounding the value of our model's parameters. RESULTS: The total mean (standard deviation (SD) cost of MT was €6708.9 (2357.0). The incremental cost-effectiveness ratio (ICER) of the strategy using IV-tPA combined to MT costs was €14,715 per QALY gained as compared to a strategy using IV-tPA alone. The probabilistic analysis showed that the probability of MT-IV-TPA being cost-effective was 85.4% at threshold willingness-to-pay of €30,000 per QALY gained, reaching 98% at €50,000 per QALY gained. CONCLUSION: Although there is no universally accepted willingness-to-pay threshold in France, our analysis suggest that MT combined to IV-tPA can be considered a cost-effective treatment compared with IV-tPA alone.