Impact of the Thrombectomy Trials on the Management and Outcome of Large Vessel Stroke: Data From the Lyon Stroke Center

Introduction: Randomized trials (RT) have recently validated the superiority of thrombectomy over standard medical care, including intravenous thrombolysis (IVT). However, data on their impact on routine clinical care remains scarce.Methods: Using a prospective observational registry, we assessed: (1) the clinical and radiological characteristics of all consecutive patients treated with thrombectomy; (2) the outcome of all patients with M1 occlusion (treated with thrombectomy or IVT alone). Two periods were compared: before (2013–2014) and after (2015–2016) the publication of RT.Results: Endovascular procedures significantly increased between the two periods (N = 82 vs. 314, p < 0.0001). In 2015–2016, patients were older (median [IQR]: 69 [57-80]; vs. 66 [53-74]; p = 0.008), had shorter door-to-clot times (69 [47-95]; vs. 110 [83-155]; p < 0.0001) resulting in a trend toward shorter delay from symptom onset to reperfusion (232 [185-300]; vs. 250 [200-339]; p = 0.1), with higher rates of reperfusion (71 vs. 48%; p = 0.0001). Conversely, no significant differences in baseline NIHSS scores, ASPECTS, delay to IVT or intracranial hemorrhage were found. In 2015–2016, patients with M1 occlusion were treated with thrombectomy more often than in 2013–2014 (87 vs. 32%, respectively; p < 0.0001), with a significant improvement in clinical outcome (shift analysis, lower modified Rankin scale scores: OR = 1.68; 95% CI: 1.10–2.57; p = 0.017).Conclusion: Following the publication of RT, thrombectomy was rapidly implemented with significant improvements in intrahospital delay and reperfusion rates. Treatment with thrombectomy increased with better clinical outcomes in patients with M1 occlusion

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (+/- SD) of 5.3 +/- 2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P = 0.02). The number of serious adverse events did not differ significantly between the treatment groups (P = 0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial.

BACKGROUND We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER URL: https://www. CLINICALTRIALS gov ; Unique identifier: NCT03192332

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Ischémie-reperfusion cérébrale : rôle de l’inflammation

Ntravenous thrombolysis and, more recently, mechanical thrombectomy have improved acute ischemic stroke management in improving restoration of brain perfusion and the preservation of the penumbra and thus functional outcome. Despite early recanalisation, a poor clinical outcome likely related to ischemia-reperfusion damages is frequently observed. Post-ischemic inflammatory response may contribute to these damages. To date, little is known about the kinetics of this process, especially in the setting of mechanical thrombectomy, whereas a better understanding of that phenomenom would allow a more targeted neuroprotective approach. Here, we proposed to assess the relationship between serum markers of inflammation and key prognostic factors, through an original approach focused on patients treated with mechanical thrombectomy. For this, we did a sequential assessement of both serum markers of inflammation and ischemic damages on magnetic resonance imaging within the HIBISCUS-STROKE cohort (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke). In the first part of our work, we aimed to clarify the relationship between post-ischemic inflammation and collateral circulation status, as the latter impacts the timing of tissue loss and response to reperfusion therapies in acute ischemic stroke. We have etablished that low Matrix Metalloproteinase-9 (MMP-9) and high Monocyte Chemoattractant Protein-1 levels were associated with good pretreatment collateral status. In the second part of our work, we assessed the relationship between MMP-9, a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and the risk of hemorrhagic transformation and infarct growth. We have identified that MMP-9 peaked at 6 hours and that its level predicted hemorrhagic transformation, mainly minor, and infarct growth. In the third part, we aimed to investigate the relationship between post-ischemic inflammation and futile recanalization, defined as poor functional outcome despite successful recanalization and occurring in half of the patients. We observed that interleukin 6 peaked at 24 hours and was a marker of futile recanalization. HIBISCUS-STROKE cohort gave us the opportunity to assess the relationship between serum markers of inflammation and key prognostic factors in the setting of mechanical thrombectomy. This original approach pave the way for new perspectives in terms of neuroprotectionLa thrombolyse intraveineuse et, plus récemment la thrombectomie mécanique, ont bouleversé la prise en charge de l’infarctus cérébral. Le principal objectif de ces thérapeutiques est de restaurer la perfusion cérébrale et de préserver la pénombre et ainsi de réduire le handicap neurologique. Cependant en dépit d’une recanalisation artérielle précoce, l’évolution clinique demeure péjorative chez certains patients probablement du fait des lésions d’ischémie/reperfusion auxquelles contribue l’inflammation. A ce jour la dynamique de la réponse inflammatoire reste peu documentée, en particulier dans le cadre de la thrombectomie mécanique. Une meilleure connaissance de ce phénomène autoriserait une approche plus ciblée de la neuroprotection dans l’ischémie cérébrale. Notre travail de thèse se propose d’étudier la relation entre les marqueurs sériques de l’inflammation et les facteurs clefs du pronostic clinique, ce qui est une approche inédite dans le contexte de la thrombectomie. Dans cette perspective, nous avons couplé au sein de la cohorte HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) l’analyse dynamique des marqueurs sériques de l’inflammation à l’évaluation séquentielle des lésions ischémiques en imagerie par résonance magnétique. Dans la première partie de ce travail nous nous sommes interrogés sur la relation entre la réponse inflammatoire et la qualité de la circulation collatérale, cette dernière étant impliquée dans la rapidité de progression de l’infarctus et la réponse à la thrombectomie. Nous avons mis en évidence qu’une collatéralité leptoméningée de bonne qualité à l’admission était associée à des taux faibles de métalloprotéase matricielle 9 (MMP-9 : Matrix Metalloproteinase-9) et à des taux élevés de Monocyte Chemoattractant Protein-1. Dans la deuxième partie de notre travail, nous avons évalué la relation entre la MMP-9, une enzyme protéolytique impliquée dans la dégradation de la barrière hémato-encéphalique, et le risque de transformation hémorragique et la croissance de l’infarctus. Nous avons observé que le taux de MMP-9 était maximal à 6 heures et que ce taux était associé à un risque accru de transformation hémorragique mais le plus souvent mineure, et à la croissance de l’infarctus cérébral. Dans la troisième partie de notre travail, nous avons souhaité précisé la relation entre l’inflammation et la recanalisation dite « futile », c’est-à-dire sans bénéfice clinique, constatée chez la moitié des patients. Nous avons révélé que le taux d’interleukine 6, maximal 24 heures après l’admission, était un facteur prédictif de recanalisation dite «futile». La cohorte HIBISCUS-STROKE nous a donc permis d’identifier les marqueurs sériques de l’inflammation associés aux facteurs clefs du pronostic clinique dans le cadre de la thrombectomie. Cette approche est susceptible de générer de nouvelles perspectives thérapeutique

Cerebral ischemia-reperfusion : role of inflammation

La thrombolyse intraveineuse et, plus récemment la thrombectomie mécanique, ont bouleversé la prise en charge de l’infarctus cérébral. Le principal objectif de ces thérapeutiques est de restaurer la perfusion cérébrale et de préserver la pénombre et ainsi de réduire le handicap neurologique. Cependant en dépit d’une recanalisation artérielle précoce, l’évolution clinique demeure péjorative chez certains patients probablement du fait des lésions d’ischémie/reperfusion auxquelles contribue l’inflammation. A ce jour la dynamique de la réponse inflammatoire reste peu documentée, en particulier dans le cadre de la thrombectomie mécanique. Une meilleure connaissance de ce phénomène autoriserait une approche plus ciblée de la neuroprotection dans l’ischémie cérébrale. Notre travail de thèse se propose d’étudier la relation entre les marqueurs sériques de l’inflammation et les facteurs clefs du pronostic clinique, ce qui est une approche inédite dans le contexte de la thrombectomie. Dans cette perspective, nous avons couplé au sein de la cohorte HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) l’analyse dynamique des marqueurs sériques de l’inflammation à l’évaluation séquentielle des lésions ischémiques en imagerie par résonance magnétique. Dans la première partie de ce travail nous nous sommes interrogés sur la relation entre la réponse inflammatoire et la qualité de la circulation collatérale, cette dernière étant impliquée dans la rapidité de progression de l’infarctus et la réponse à la thrombectomie. Nous avons mis en évidence qu’une collatéralité leptoméningée de bonne qualité à l’admission était associée à des taux faibles de métalloprotéase matricielle 9 (MMP-9 : Matrix Metalloproteinase-9) et à des taux élevés de Monocyte Chemoattractant Protein-1. Dans la deuxième partie de notre travail, nous avons évalué la relation entre la MMP-9, une enzyme protéolytique impliquée dans la dégradation de la barrière hémato-encéphalique, et le risque de transformation hémorragique et la croissance de l’infarctus. Nous avons observé que le taux de MMP-9 était maximal à 6 heures et que ce taux était associé à un risque accru de transformation hémorragique mais le plus souvent mineure, et à la croissance de l’infarctus cérébral. Dans la troisième partie de notre travail, nous avons souhaité précisé la relation entre l’inflammation et la recanalisation dite « futile », c’est-à-dire sans bénéfice clinique, constatée chez la moitié des patients. Nous avons révélé que le taux d’interleukine 6, maximal 24 heures après l’admission, était un facteur prédictif de recanalisation dite «futile». La cohorte HIBISCUS-STROKE nous a donc permis d’identifier les marqueurs sériques de l’inflammation associés aux facteurs clefs du pronostic clinique dans le cadre de la thrombectomie. Cette approche est susceptible de générer de nouvelles perspectives thérapeutiquesNtravenous thrombolysis and, more recently, mechanical thrombectomy have improved acute ischemic stroke management in improving restoration of brain perfusion and the preservation of the penumbra and thus functional outcome. Despite early recanalisation, a poor clinical outcome likely related to ischemia-reperfusion damages is frequently observed. Post-ischemic inflammatory response may contribute to these damages. To date, little is known about the kinetics of this process, especially in the setting of mechanical thrombectomy, whereas a better understanding of that phenomenom would allow a more targeted neuroprotective approach. Here, we proposed to assess the relationship between serum markers of inflammation and key prognostic factors, through an original approach focused on patients treated with mechanical thrombectomy. For this, we did a sequential assessement of both serum markers of inflammation and ischemic damages on magnetic resonance imaging within the HIBISCUS-STROKE cohort (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke). In the first part of our work, we aimed to clarify the relationship between post-ischemic inflammation and collateral circulation status, as the latter impacts the timing of tissue loss and response to reperfusion therapies in acute ischemic stroke. We have etablished that low Matrix Metalloproteinase-9 (MMP-9) and high Monocyte Chemoattractant Protein-1 levels were associated with good pretreatment collateral status. In the second part of our work, we assessed the relationship between MMP-9, a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and the risk of hemorrhagic transformation and infarct growth. We have identified that MMP-9 peaked at 6 hours and that its level predicted hemorrhagic transformation, mainly minor, and infarct growth. In the third part, we aimed to investigate the relationship between post-ischemic inflammation and futile recanalization, defined as poor functional outcome despite successful recanalization and occurring in half of the patients. We observed that interleukin 6 peaked at 24 hours and was a marker of futile recanalization. HIBISCUS-STROKE cohort gave us the opportunity to assess the relationship between serum markers of inflammation and key prognostic factors in the setting of mechanical thrombectomy. This original approach pave the way for new perspectives in terms of neuroprotectio

Ischémie-reperfusion cérébrale : rôle de l’inflammation

Ntravenous thrombolysis and, more recently, mechanical thrombectomy have improved acute ischemic stroke management in improving restoration of brain perfusion and the preservation of the penumbra and thus functional outcome. Despite early recanalisation, a poor clinical outcome likely related to ischemia-reperfusion damages is frequently observed. Post-ischemic inflammatory response may contribute to these damages. To date, little is known about the kinetics of this process, especially in the setting of mechanical thrombectomy, whereas a better understanding of that phenomenom would allow a more targeted neuroprotective approach. Here, we proposed to assess the relationship between serum markers of inflammation and key prognostic factors, through an original approach focused on patients treated with mechanical thrombectomy. For this, we did a sequential assessement of both serum markers of inflammation and ischemic damages on magnetic resonance imaging within the HIBISCUS-STROKE cohort (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke). In the first part of our work, we aimed to clarify the relationship between post-ischemic inflammation and collateral circulation status, as the latter impacts the timing of tissue loss and response to reperfusion therapies in acute ischemic stroke. We have etablished that low Matrix Metalloproteinase-9 (MMP-9) and high Monocyte Chemoattractant Protein-1 levels were associated with good pretreatment collateral status. In the second part of our work, we assessed the relationship between MMP-9, a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and the risk of hemorrhagic transformation and infarct growth. We have identified that MMP-9 peaked at 6 hours and that its level predicted hemorrhagic transformation, mainly minor, and infarct growth. In the third part, we aimed to investigate the relationship between post-ischemic inflammation and futile recanalization, defined as poor functional outcome despite successful recanalization and occurring in half of the patients. We observed that interleukin 6 peaked at 24 hours and was a marker of futile recanalization. HIBISCUS-STROKE cohort gave us the opportunity to assess the relationship between serum markers of inflammation and key prognostic factors in the setting of mechanical thrombectomy. This original approach pave the way for new perspectives in terms of neuroprotectionLa thrombolyse intraveineuse et, plus récemment la thrombectomie mécanique, ont bouleversé la prise en charge de l’infarctus cérébral. Le principal objectif de ces thérapeutiques est de restaurer la perfusion cérébrale et de préserver la pénombre et ainsi de réduire le handicap neurologique. Cependant en dépit d’une recanalisation artérielle précoce, l’évolution clinique demeure péjorative chez certains patients probablement du fait des lésions d’ischémie/reperfusion auxquelles contribue l’inflammation. A ce jour la dynamique de la réponse inflammatoire reste peu documentée, en particulier dans le cadre de la thrombectomie mécanique. Une meilleure connaissance de ce phénomène autoriserait une approche plus ciblée de la neuroprotection dans l’ischémie cérébrale. Notre travail de thèse se propose d’étudier la relation entre les marqueurs sériques de l’inflammation et les facteurs clefs du pronostic clinique, ce qui est une approche inédite dans le contexte de la thrombectomie. Dans cette perspective, nous avons couplé au sein de la cohorte HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) l’analyse dynamique des marqueurs sériques de l’inflammation à l’évaluation séquentielle des lésions ischémiques en imagerie par résonance magnétique. Dans la première partie de ce travail nous nous sommes interrogés sur la relation entre la réponse inflammatoire et la qualité de la circulation collatérale, cette dernière étant impliquée dans la rapidité de progression de l’infarctus et la réponse à la thrombectomie. Nous avons mis en évidence qu’une collatéralité leptoméningée de bonne qualité à l’admission était associée à des taux faibles de métalloprotéase matricielle 9 (MMP-9 : Matrix Metalloproteinase-9) et à des taux élevés de Monocyte Chemoattractant Protein-1. Dans la deuxième partie de notre travail, nous avons évalué la relation entre la MMP-9, une enzyme protéolytique impliquée dans la dégradation de la barrière hémato-encéphalique, et le risque de transformation hémorragique et la croissance de l’infarctus. Nous avons observé que le taux de MMP-9 était maximal à 6 heures et que ce taux était associé à un risque accru de transformation hémorragique mais le plus souvent mineure, et à la croissance de l’infarctus cérébral. Dans la troisième partie de notre travail, nous avons souhaité précisé la relation entre l’inflammation et la recanalisation dite « futile », c’est-à-dire sans bénéfice clinique, constatée chez la moitié des patients. Nous avons révélé que le taux d’interleukine 6, maximal 24 heures après l’admission, était un facteur prédictif de recanalisation dite «futile». La cohorte HIBISCUS-STROKE nous a donc permis d’identifier les marqueurs sériques de l’inflammation associés aux facteurs clefs du pronostic clinique dans le cadre de la thrombectomie. Cette approche est susceptible de générer de nouvelles perspectives thérapeutique

Ischémie-reperfusion cérébrale : rôle de l’inflammation

Ntravenous thrombolysis and, more recently, mechanical thrombectomy have improved acute ischemic stroke management in improving restoration of brain perfusion and the preservation of the penumbra and thus functional outcome. Despite early recanalisation, a poor clinical outcome likely related to ischemia-reperfusion damages is frequently observed. Post-ischemic inflammatory response may contribute to these damages. To date, little is known about the kinetics of this process, especially in the setting of mechanical thrombectomy, whereas a better understanding of that phenomenom would allow a more targeted neuroprotective approach. Here, we proposed to assess the relationship between serum markers of inflammation and key prognostic factors, through an original approach focused on patients treated with mechanical thrombectomy. For this, we did a sequential assessement of both serum markers of inflammation and ischemic damages on magnetic resonance imaging within the HIBISCUS-STROKE cohort (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke). In the first part of our work, we aimed to clarify the relationship between post-ischemic inflammation and collateral circulation status, as the latter impacts the timing of tissue loss and response to reperfusion therapies in acute ischemic stroke. We have etablished that low Matrix Metalloproteinase-9 (MMP-9) and high Monocyte Chemoattractant Protein-1 levels were associated with good pretreatment collateral status. In the second part of our work, we assessed the relationship between MMP-9, a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and the risk of hemorrhagic transformation and infarct growth. We have identified that MMP-9 peaked at 6 hours and that its level predicted hemorrhagic transformation, mainly minor, and infarct growth. In the third part, we aimed to investigate the relationship between post-ischemic inflammation and futile recanalization, defined as poor functional outcome despite successful recanalization and occurring in half of the patients. We observed that interleukin 6 peaked at 24 hours and was a marker of futile recanalization. HIBISCUS-STROKE cohort gave us the opportunity to assess the relationship between serum markers of inflammation and key prognostic factors in the setting of mechanical thrombectomy. This original approach pave the way for new perspectives in terms of neuroprotectionLa thrombolyse intraveineuse et, plus récemment la thrombectomie mécanique, ont bouleversé la prise en charge de l’infarctus cérébral. Le principal objectif de ces thérapeutiques est de restaurer la perfusion cérébrale et de préserver la pénombre et ainsi de réduire le handicap neurologique. Cependant en dépit d’une recanalisation artérielle précoce, l’évolution clinique demeure péjorative chez certains patients probablement du fait des lésions d’ischémie/reperfusion auxquelles contribue l’inflammation. A ce jour la dynamique de la réponse inflammatoire reste peu documentée, en particulier dans le cadre de la thrombectomie mécanique. Une meilleure connaissance de ce phénomène autoriserait une approche plus ciblée de la neuroprotection dans l’ischémie cérébrale. Notre travail de thèse se propose d’étudier la relation entre les marqueurs sériques de l’inflammation et les facteurs clefs du pronostic clinique, ce qui est une approche inédite dans le contexte de la thrombectomie. Dans cette perspective, nous avons couplé au sein de la cohorte HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) l’analyse dynamique des marqueurs sériques de l’inflammation à l’évaluation séquentielle des lésions ischémiques en imagerie par résonance magnétique. Dans la première partie de ce travail nous nous sommes interrogés sur la relation entre la réponse inflammatoire et la qualité de la circulation collatérale, cette dernière étant impliquée dans la rapidité de progression de l’infarctus et la réponse à la thrombectomie. Nous avons mis en évidence qu’une collatéralité leptoméningée de bonne qualité à l’admission était associée à des taux faibles de métalloprotéase matricielle 9 (MMP-9 : Matrix Metalloproteinase-9) et à des taux élevés de Monocyte Chemoattractant Protein-1. Dans la deuxième partie de notre travail, nous avons évalué la relation entre la MMP-9, une enzyme protéolytique impliquée dans la dégradation de la barrière hémato-encéphalique, et le risque de transformation hémorragique et la croissance de l’infarctus. Nous avons observé que le taux de MMP-9 était maximal à 6 heures et que ce taux était associé à un risque accru de transformation hémorragique mais le plus souvent mineure, et à la croissance de l’infarctus cérébral. Dans la troisième partie de notre travail, nous avons souhaité précisé la relation entre l’inflammation et la recanalisation dite « futile », c’est-à-dire sans bénéfice clinique, constatée chez la moitié des patients. Nous avons révélé que le taux d’interleukine 6, maximal 24 heures après l’admission, était un facteur prédictif de recanalisation dite «futile». La cohorte HIBISCUS-STROKE nous a donc permis d’identifier les marqueurs sériques de l’inflammation associés aux facteurs clefs du pronostic clinique dans le cadre de la thrombectomie. Cette approche est susceptible de générer de nouvelles perspectives thérapeutique

Pollution atmosphérique et infarctus cérébraux (l'étude AVC69)

LYON1-BU Santé (693882101) / SudocSudocFranceF

The Elusive Origin of Atherosclerotic Plaque Calcification

International audienceIt has been known for decades or even centuries that arteries calcify as they age. Vascular calcification probably affects all adults, since virtually all have atherosclerotic plaques: an accumulation of lipids, inflammatory cells, necrotic debris, and calcium phosphate crystals. A high vascular calcium score is associated with a high cardiovascular mortality risk, and relatively recent data suggest that even microcalcifications that form in early plaques may destabilize plaques and trigger a cardiovascular event. If the cellular and molecular mechanisms of plaque calcification have been relatively well characterized in mice, human plaques appear to calcify through different mechanisms that remain obscure. In this context, we will first review articles reporting the location and features of early calcifications in human plaques and then review the articles that explored the mechanisms though which human and mouse plaques calcify