Publications by authors named "Jean-Philippe Desilles"

65 Publications

Timing and Spectrum of Neurological Complications After Flow Diverter Implantation for Intracranial Aneurysms.

Front Neurol 2021 20;12:590383. Epub 2021 Apr 20.

Interventional Neuroradiology, Rothschild Foundation Hospital, Paris, France.

The aim of this study was to characterize neurological complications after flow diverter (FD) treatment on a long follow-up cohort and identify predictive factors associated with these complications. This study was conducted on a monocentric cohort of patients treated for intracranial aneurysms by FD. Between September 2008 and July 2018, 413 patients were treated for 514 aneurysms: 18% of the patients presented with at least one neurological complication during a median follow-up of 446 days (IQR 186-1,210). Sixty-one patients presented with ischemic complications, 13 with hemorrhagic ones and 10 with compressive processes. Among 89 neurological complications 64.5% were peri-operative (occurring within the 30 days following the procedure) and 35.5% were delayed after 1 month. Overall, neurological complications after FD implantation were overrepresented by cerebrovascular ischemic events occurring during the peri-operative period, but also in a delayed manner after 1 year. Long-term follow-up is relevant after aneurysm intervention using FD.
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http://dx.doi.org/10.3389/fneur.2021.590383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093792PMC
April 2021

Intravenous abciximab as a rescue therapy for immediate reocclusion after successful mechanical thrombectomy in acute ischemic stroke patients.

Platelets 2021 Apr 11:1-6. Epub 2021 Apr 11.

Rothschild Foundation Hospital, Interventional Neuroradiology Department, Paris, France.

- Immediate reocclusion after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a rare but devastating condition associated with poor functional outcome. - The aim of this study was to gain insights into the mechanisms underlying immediate reocclusion, and to evaluate the efficacy and safety of the glycoprotein IIb/IIIa antagonist abciximab, for its treatment. - Clinical data were collected from April 2015 to April 2019 in a monocentric prospective registry of AIS patients treated by MT. All patients with immediate reocclusion were retrospectively selected and subdivided into 2 groups according to abciximab treatment status. , the separate and combined effects of abciximab and alteplase on clot formation in whole blood under flow conditions were further investigated in microfluidic chambers. - From 929 MT-treated patients, 21 had post-MT immediate reocclusion. Abciximab treatment in reocclusion patients (n = 10) led to higher rate of final recanalization ( < .001) while it did not increase bleeding complications. Flow chamber experiments revealed that, in contrast to alteplase, abciximab efficiently limits thrombus accretion from flowing blood by blocking platelet aggregation. - Our results underscore a key role for platelet aggregation and the potential of Glycoprotein IIb/IIIa antagonists as a rescue therapy in post-MT immediate reocclusion.
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http://dx.doi.org/10.1080/09537104.2021.1894326DOI Listing
April 2021

A Novel Mouse Model for Cerebral Venous Sinus Thrombosis.

Transl Stroke Res 2021 Mar 5. Epub 2021 Mar 5.

Laboratory for Vascular Translational Science (LVTS), INSERM UMR 1148, Université de Paris, 75018, Paris, France.

Cerebral venous sinus thrombosis (CVST) is an uncommon cause of stroke resulting in parenchymal injuries associated with heterogeneous clinical symptoms and prognosis. Therefore, an experimental animal model is required to further study underlying mechanisms involved in CVST. This study is aimed at developing a novel murine model suitable and relevant for evaluating injury patterns during CVST and studying its clinical aspects. CVST was achieved in C57BL/6J mice by autologous clot injection into the superior sagittal sinus (SSS) combined with bilateral ligation of external jugular veins. Clot was prepared ex vivo using thrombin before injection. On days 1 and 7 after CVST, SSS occlusion and associated-parenchymal lesions were monitored using different modalities: in vivo real-time intravital microscopy, magnetic resonance imaging (MRI), and immuno-histology. In addition, mice were subjected to a neurological sensory-motor evaluation. Thrombin-induced clot provided fibrin- and erythrocyte-rich thrombi that lead to reproducible SSS occlusion at day 1 after CVST induction. On day 7 post-CVST, venous occlusion monitoring (MRI, intravital microscopy) showed that initial injected-thrombus size did not significantly change demonstrating no early spontaneous recanalization. Microscopic histological analysis revealed that SSS occlusion resulted in brain edema, extensive fibrin-rich venular thrombotic occlusion, and ischemic and hemorrhagic lesions. Mice with CVST showed a significant lower neurological score on post-operative days 1 and 7, compared to the sham-operated group. We established a novel clinically CVST-relevant model with a persistent and reproducible SSS occlusion responsible for symptomatic ischemic and hemorrhagic lesions. This method provides a reliable model to study CVST physiopathology and evaluation of therapeutic new regimens.
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http://dx.doi.org/10.1007/s12975-021-00898-1DOI Listing
March 2021

Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial.

Lancet Neurol 2021 04 26;20(4):265-274. Epub 2021 Feb 26.

Department of Interventional Neuroradiology, Rothschild Foundation Hospital, Paris, France; Laboratory of Vascular Translational Science, INSERM, Paris, France; FHU NeuroVasc, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target.

Methods: We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100-129 mm Hg) or a standard care systolic blood pressure target group (130-185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24-36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov, number NCT03160677, and the trial is closed at all participating sites.

Findings: Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24-36 h after reperfusion] (adjusted odds ratio 0·96, 95% CI 0·60-1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group.

Interpretation: An intensive systolic blood pressure target of 100-129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24-36 h as compared with a standard care systolic blood pressure target of 130-185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion.

Funding: French Health Ministry.
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http://dx.doi.org/10.1016/S1474-4422(20)30483-XDOI Listing
April 2021

Intracranial Hemorrhage After Reperfusion Therapies in Acute Ischemic Stroke Patients.

Front Neurol 2020 11;11:599908. Epub 2020 Dec 11.

Interventional Neuroradiology Department, Hôpital Fondation Adolphe de Rothschild, Paris, France.

Reperfusion therapies are the mainstay of acute ischemic stroke (AIS) treatments and overall improve functional outcome. Among the established complications of intravenous (IV) tissue-type plasminogen activator (tPA), intracranial hemorrhage (ICH) is by far the most feared and has been extensively described by seminal works over the last two decades. Indeed, IV tPA is associated with increased odds of any ICH and symptomatic ICH responsible for increased mortality rate during the first week after an AIS. Despite these results, IV tPA has been found beneficial in several pioneering randomized trials and improves functional outcome at 3 months. Endovascular therapy (EVT) combined with IV tPA for AIS patients consecutive to an anterior circulation large-vessel occlusion does not increase ICH occurrence. Of note, EVT following IV tPA leads to significantly higher rates of early reperfusion than with IV tPA alone, with no difference in ICH, which challenges the paradigm of reperfusion as a major prognostic factor for ICH complications. However, several blood biomarkers (glycemia, platelet and neutrophil count), clinical factors (age, AIS severity, blood pressure management, diabetes mellitus), and neuroradiological factors (cerebral microbleeds, infarct size) have been identified as risk factors for ICH after reperfusion therapy. In the years to come, the ultimate goal will be to further improve either reperfusion rates and functional outcome, while reducing hemorrhagic complications. To this end, various approaches being investigated are discussed in this review, such as blood-pressure control after reperfusion or the use of new antiplatelet agents as an adjunct to IV tPA and exhibit reduced hemorrhagic potential during the early phase of AIS.
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http://dx.doi.org/10.3389/fneur.2020.599908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759548PMC
December 2020

Corrigendum to 'Antiplatelet Therapy During Emergent Extracranial Internal Carotid Artery Stenting: Comparison of Three Intravenous Antiplatelet Perioperative Strategies' [Journal of Stroke and Cerebrovascular Diseases, Vol. 30, No. 2, (2020) 105521].

J Stroke Cerebrovasc Dis 2021 Mar 22;30(3):105560. Epub 2020 Dec 22.

Interventional Neuroradiology Department, Rothschild Foundation Hospital, Paris, France; Laboratory of Vascular Translational Sci- ence, U1148 INSERM, Universit'e de Paris, 46 rue Henri Huchard 75018 Paris, France; Universit'e de Paris, France; FHU Neurovasc, France. Electronic address:

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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105560DOI Listing
March 2021

Antiplatelet Therapy During Emergent Extracranial Internal Carotid Artery Stenting: Comparison of Three Intravenous Antiplatelet Perioperative Strategies.

J Stroke Cerebrovasc Dis 2021 Feb 9;30(2):105521. Epub 2020 Dec 9.

Interventional Neuroradiology Department, Rothschild Foundation Hospital, Paris, France; Laboratory of Vascular Translational Science, U1148 INSERM, Université de Paris, 46 rue Henri Huchard 75018 Paris, France; Université de Paris, France; FHU Neurovasc, France. Electronic address:

Introduction: Guidelines for antiplatelet therapy administration, during emergent stenting for extra-cranial internal carotid artery (EC-ICA) occlusion in the setting of acute ischemic stroke (AIS) are lacking. Different antiplatelet regimen are used in association to endovascular therapy (EVT) for the treatment of EC-ICA lesions. We aimed to compare the clinical and radiological effects of three intravenous antiplatelet agents used during emergent EC-ICA stenting.

Material And Methods: Clinical data were collected from January 2015 to December 2019 in a monocentric prospective registry of AIS patients treated by EVT. All patients who underwent emergent EC-ICA stenting were sorted regarding the intravenous antiplatelet agent used during the procedure.

Results: Among 218 patients treated by EVT for an EC-ICA occlusion of the anterior circulation during the study period, 70 underwent an emergent stenting of the EC-ICA. 60 were included in the present study, 9 received intravenous (IV) Cangrelor, 8 IV abciximab and 43 Aspirin. The rate of favorable neurological outcome, defined as modified Rankin Scale (mRS) ≤ 2 at three months were better in the Cangrelor and Aspirin groups (66,7% and 58,1%, respectively) than in the Abciximab group (37,5%), as well as, the rate of any intracranial ICH (22,2% and 37,2% vs 62,5%). The rate of acute stent reocclusion was similar between groups.

Conclusion: When used as a rescue treatment during emergent stenting of EC-ICA, Cangrelor and Aspirin present a better safety profile than Abciximab, with less intracranial hemorrhages and a higher rate of good clinical outcome. Additional studies are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105521DOI Listing
February 2021

Corrigendum to 'Benefits and Safety of Periprocedural Heparin During Thrombectomy in Patients Contra-Indicated for Alteplase' [Journal of Stroke and Cerebrovascular Diseases, Vol. 29, No. 10 (October), 2020: 105052].

J Stroke Cerebrovasc Dis 2021 Feb 9;30(2):105465. Epub 2020 Dec 9.

Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France; Laboratory of Vascular Translational Science, U1148 Institut National de la Sant'e et de la Recherche M'edicale (INSERM), Paris, France; Universit'e Paris Denis Diderot, Sorbonne Paris Cite, France.

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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105465DOI Listing
February 2021

Impact of Blood Pressure After Successful Endovascular Therapy for Anterior Acute Ischemic Stroke: A Systematic Review.

Front Neurol 2020 29;11:573382. Epub 2020 Oct 29.

Interventional Neuroradiology Department, Fondation Rothschild, Paris, France.

Optimal blood pressure (BP) targets after endovascular therapy (EVT) for acute ischemic stroke (AIS) still need to be assessed, especially according to the recanalization status. Facing the lack of randomized controlled trials addressing this question, we performed a systematic review of studies assessing the post-EVT BP impact on functional outcome and symptomatic intracranial hemorrhage (sICH). Studies published after January 1, 2012 were included in the systematic review. The PRISMA checklist and flow diagram were followed for the design and reporting of this work. Five studies were included in the present analysis. Despite a significant heterogeneity among studies which precluded a meta-analysis, systolic BP (SBP) was the most frequently used parameter to describe BP. BP variability (standard deviation, successive variability) after EVT was associated with worse functional outcome, especially in studies without specific BP targets after successful EVT. Lower BP values after successful EVT were associated with lower odds of sICH. Four studies evaluated the post-EVT BP impact on recanalized patients solely, with only one specifically addressing the impact of a TICI 2B vs. 2C. Interestingly, SBP reduction was inversely associated with worse outcomes in TICI 3 patients but not in TICI 2B patients, pointing to the potential value of BP management according to the exact TICI. BP post-EVT seems to be associated with worse functional outcomes and sICH. However, given the important heterogeneity depicted among the included studies, no decisive conclusion can be made from this systematic review, thus underlying the urgent need of randomized controlled trials evaluating this question.
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http://dx.doi.org/10.3389/fneur.2020.573382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659685PMC
October 2020

Location of intracranial aneurysms is the main factor associated with rupture in the ICAN population.

J Neurol Neurosurg Psychiatry 2021 02 23;92(2):122-128. Epub 2020 Oct 23.

Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Nantes, L'institut du thorax, Inserm 1087, CNRS, UNIV Nantes, Nantes, Pays de la Loire, FR, University Hospital Centre Nantes, Nantes, Pays de la Loire, France

Background And Purpose: The ever-growing availability of imaging led to increasing incidentally discovered unruptured intracranial aneurysms (UIAs). We leveraged machine-learning techniques and advanced statistical methods to provide new insights into rupture intracranial aneurysm (RIA) risks.

Methods: We analysed the characteristics of 2505 patients with intracranial aneurysms (IA) discovered between 2016 and 2019. Baseline characteristics, familial history of IA, tobacco and alcohol consumption, pharmacological treatments before the IA diagnosis, cardiovascular risk factors and comorbidities, headaches, allergy and atopy, IA location, absolute IA size and adjusted size ratio (aSR) were analysed with a multivariable logistic regression (MLR) model. A random forest (RF) method globally assessed the risk factors and evaluated the predictive capacity of a multivariate model.

Results: Among 994 patients with RIA (39.7%) and 1511 patients with UIA (60.3 %), the MLR showed that IA location appeared to be the most significant factor associated with RIA (OR, 95% CI: internal carotid artery, reference; middle cerebral artery, 2.72, 2.02-3.58; anterior cerebral artery, 4.99, 3.61-6.92; posterior circulation arteries, 6.05, 4.41-8.33). Size and aSR were not significant factors associated with RIA in the MLR model and antiplatelet-treatment intake patients were less likely to have RIA (OR: 0.74; 95% CI: 0.55-0.98). IA location, age, following by aSR were the best predictors of RIA using the RF model.

Conclusions: The location of IA is the most consistent parameter associated with RIA. The use of 'artificial intelligence' RF helps to re-evaluate the contribution and selection of each risk factor in the multivariate model.
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http://dx.doi.org/10.1136/jnnp-2020-324371DOI Listing
February 2021

Rescue carotid puncture for ischemic stroke treated by endovascular therapy: a multicentric analysis and systematic review.

J Neurointerv Surg 2020 Oct 19. Epub 2020 Oct 19.

Interventional Neuroradiology, Fondation Ophtalmologique Adolphe de Rothschild, Paris, Île-de-France, France.

Background: Endovascular therapy (EVT) for acute ischemic stroke (AIS) can be challenging in older patients with supra-aortic tortuosity. Rescue carotid puncture (RCP) can be an alternative in case of supra-aortic catheterization failure by femoral access, but data regarding RCP are scarce. We sought to investigate the feasibility, effectiveness and safety of RCP for AIS treated by EVT.

Methods: Patients treated by EVT with RCP were included from January 2012 to December 2019 in the Endovascular Treatment in Ischemic Stroke (ETIS) multicentric registry. Main outcomes included reperfusion rates (≥TICI2B), 3 month functional outcome (modified Rankin Scale) and 3 month mortality. We also performed an additional systematic review of the literature according to the PRISMA checklist to summarize previous studies on RCP.

Results: 25 patients treated by EVT with RCP were included from the ETIS registry. RCP mainly concerned elderly patients (median age 85 years, range 73-92) with supra-aortic tortuosity (n=16 (64%)). Intravenous thrombolysis (IVT) was used for nine patients (36%). Successful reperfusion was achieved in 64%, 87.5% of patients were dependent at 3 months, and 3 month mortality was 45.8%. The systematic review yielded comparable results. In pooled individual data, there was a shift toward better functional outcome in patients with successful reperfusion (median (IQR) 4 (2-6) vs 6 (4-6), p=0.011).

Conclusion: RCP mainly concerned elderly patients admitted for AIS with anterior LVO with supra-aortic tortuosity. The procedure seemed feasible, notably for patients treated with IVT, and led to significant reperfusion rates at the end of procedure, but with pronounced unfavorable outcomes at 3 months. RCP should be performed under general anesthesia to avoid life-threatening complications and ensure airways safety. Finally, RCP led to low rates of closure complications, emphasizing that this concern should not withhold RCP, if indicated.
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http://dx.doi.org/10.1136/neurintsurg-2020-016725DOI Listing
October 2020

Diagnostic Performances of the Susceptibility Vessel Sign on MRI for the Prediction of Macroscopic Thrombi Features in Acute Ischemic Stroke.

J Stroke Cerebrovasc Dis 2020 Nov 20;29(11):105245. Epub 2020 Aug 20.

Department of Diagnostic and Therapeutic Neuroradiology, Hôpital Foch Suresnes FR, University of Versailles Saint Quentin-en-Yvelines, France.

Background And Purpose: The "white" compared to "Red-Black" visual aspect of the thrombus at withdrawal with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) was related to atypical etiologies like infective endocarditis. The susceptibility vessel sign (SVS) and the two-layered SVS (TL-SVS) could help predict outcome and cardio-embolic etiology of AIS. We aim to evaluate the diagnostic performance of the SVS and TLSVS to predict the visual aspect of the thrombus.

Materials And Methods: We included patients treated by MT and screened with MRI for the SVS and the TL-SVS for whom thrombus photograph was available. Photographs underwent a double-blind evaluation by neuroradiologists who classified the thrombus as "White" or "Red-Black". Logistic regression assessed the association of Red-Black thrombus and age, sex, baseline National Institutes of Health Stroke Scale, occlusion site, the IVr-tPA administration, SVS and TL-SVS. We calculated the diagnostic performances of the SVS to predict a Red-Black type thrombus.

Results: Between May 2017 and July 2018, 139 patients were included in the study. On multivariate analysis, only SVS was an independent predictor for Red-Black thrombus (Odd ratio 8.31, 95%CI2.30 to 32, p value<0.001). Concerning SVS diagnostic performances, the specificity was 0.58 (95%CI0.28 to 0.85), the sensitivity was 0.87 (95%CI0.80 to 0.93), the negative predictive value was 0.30 (95% 0.13 to 0.53), the positive predictive value was 0.96 (95%CI0.90 to 0.99) and accuracy was 0.85 (95%CI0.78 to 0.90).

Conclusion: The SVS on MRI provides a good prediction accuracy to anticipate the macroscopic visual aspect of the thrombus after MT for AIS.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105245DOI Listing
November 2020

Endovascular treatment as the main approach for Spetzler-Martin grade III brain arteriovenous malformations.

J Neurointerv Surg 2021 Mar 28;13(3):241-246. Epub 2020 Sep 28.

Department of Interventional Neuroradiology, Fondation de Rothschild, Paris, France.

Background: Because Spetzler-Martin (SM) grade III brain arteriovenous malformations (bAVMs) constitute a heterogeneous group of lesions with various combination of sizes, eloquence, and venous drainage patterns, their management is usually challenging. The aim of this study is to evaluate the clinical/imaging outcomes and the procedural safety of endovascular approach as the main treatment for the cure of SM grade III bAVMs.

Methods: In this retrospective study, prospectively collected data of SM grade III bAVMs treated by endovascular techniques between 2010 and 2018 at our hospital were reviewed. Patients older than 16 years with angiographic follow-up of at least 6 months after endovascular treatment were entered in the study. The patients had a mean follow-up of 12 months. The data were assessed for clinical outcome (modified Rankin Scale), permanent neurological deficit, post-operative complications, and optimal imaging outcome, defined by complete exclusion of AVM. The independent predictive variables of poor outcome or hemorrhagic complication were assessed using binary logistic regression.

Results: Sixty-five patients with 65 AVMs were included in the study. Mean age of the patients was 40.0±14.4. Most common presentation was hemorrhage (61.5%). The patients underwent one to eight endovascular procedures (median=2). Mean nidus diameter was 30.2±13.0. A complete obliteration of AVM was achieved in 57 patients (87.7%). Post-procedure significant hemorrhagic and ischemic complications were seen in 13 (20%) and five (7.7%) patients respectively, leading to five (7.7%) transient and four (6.2%) permanent neurological deficits. Eight patients (12.3%) experienced worsening of mRS after embolization. Ten patients (15.4%) had poor outcome (mRS 3-5) at follow-up and two (3%) died.

Conclusions: Endovascular treatment can achieve a high rate of complete exclusion of grade III AVM but may be associated (as in other treatment modalities) with significant important complications.

Clinical Trial Registration Number: NCT02879071.
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http://dx.doi.org/10.1136/neurintsurg-2020-016450DOI Listing
March 2021

Benefits and Safety of Periprocedural Heparin During Thrombectomy in Patients Contra-Indicated for Alteplase.

J Stroke Cerebrovasc Dis 2020 Oct 18;29(10):105052. Epub 2020 Jul 18.

Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France; Laboratory of Vascular Translational Science, U1148 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France; Université Paris Denis Diderot, Sorbonne Paris Cite, France.

Backround And Purpose: Role of peri-procedural heparin as an adjuvant treatment during mechanical thrombectomy (MT) for patients contra-indicated for alteplase remains a source of debate.

Methods: We included patients from the multicenter French register ETIS that underwent MT without administration of alteplase, and compared patients who received heparin during MT with patients who did not. Heparin impact on outcome were analyzed regarding final TICI score, NIHSS at day one, modified rankin scale (mRS) and intracranial hemorrhagic transformation on imaging at day one.

Results: Over 1031 patients, 751 were included between January 2015 and June 2018 in 6 different centers, and 223 (26.69%) received heparin. Heparin administration was associated with a significant deleterious effect on NIHSS at 24h [adjusted OR = 1.2; p = 0.02], mRS at 3 months [adjusted OR 1.58; p = 0.03], and on complete reperfusion [TICI 3 adjusted OR 0.68; p = 0.02]. Heparin administration was associated with a significant reduction of hemorrhagic transformation [adjusted OR 0.48; p = 0.00005].

Conclusions: Heparin administration during MT seems deleterious for reperfusion and functional outcome. Randomized trials are needed to identify the role of antithrombotic treatments, such as heparin, in the setting of acute ischemic stroke management.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105052DOI Listing
October 2020

Selective inhibition of carboxypeptidase U may reduce microvascular thrombosis in rat experimental stroke.

J Thromb Haemost 2020 12 1;18(12):3325-3335. Epub 2020 Oct 1.

Laboratory for Vascular Translational Sciences, UMR_S1148 Inserm, University of Paris, Paris, France.

Background: Carboxypeptidase U (CPU, CPB2, TAFIa) is a potent attenuator of fibrinolysis. The inhibition of CPU is thus an interesting strategy for improving thrombolysis.

Objectives: The time course of CPU generation and proCPU consumption were assessed in an experimental rat model of acute ischemic stroke (AIS). In addition, the effects of the selective CPU inhibitor AZD9684 on CPU kinetics, microvascular thrombosis (MT), and AIS outcome were evaluated.

Methods: Rats were subjected to transient middle cerebral artery occlusion (tMCAO) and received recombinant tissue-type plasminogen activator (tPA), a specific CPU inhibitor (AZD9684), combination therapy of tPA and AZD9684, or saline for 1 hour using a randomized treatment regime. CPU and proCPU levels were determined at five time points and assessed in light of outcome parameters (a.o.: infarct volume and fibrin[ogen] deposition as a measure for MT).

Results: Clear activation of the CPU system was observed after AIS induction, in both saline- and tPA-treated rats. Maximal CPU activities were observed at treatment cessation and were higher in tPA-treated animals compared to the saline group. Concomitant proCPU consumption was more pronounced in tPA-treated rats. AZD9684 suppressed the CPU activity and reduced fibrin(ogen) deposition, suggesting a reduction of MT. Nonetheless, a significant decrease in infarct volume was not observed.

Conclusions: A pronounced activation of the CPU system was observed during tMCAO in rats. Selective inhibition of CPU with AZD9684 was able to reduce fibrin(ogen) deposition and brain edema, suggesting a reduction of MT but without a significant effect on final infarct volume.
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http://dx.doi.org/10.1111/jth.15071DOI Listing
December 2020

Early Brain Imaging Shows Increased Severity of Acute Ischemic Strokes With Large Vessel Occlusion in COVID-19 Patients.

Stroke 2020 11 19;51(11):3366-3370. Epub 2020 Aug 19.

Department of Interventional Neuroradiology, Rothschild Foundation Hospital, Paris, France (S.E., H.R., F.D., S.H., S.S., G.C., J.-P.D., M.M., R.B., B.M., M.P.).

Background And Purpose: Reports are emerging regarding the association of acute ischemic strokes with large vessel occlusion and coronavirus disease 2019 (COVID-19). While a higher severity of these patients could be expected from the addition of both respiratory and neurological injury, COVID-19 patients with strokes can present with mild or none respiratory symptoms. We aimed to compare anterior circulation large vessel occlusion strokes severity between patients with and without COVID-19.

Methods: We performed a comparative cohort study between patients with COVID-19 who had anterior circulation large vessel occlusion and early brain imaging within 3 hours from onset, in our institution during the 6 first weeks of the COVID-19 outbreak and a control group admitted during the same calendar period in 2019.

Results: Twelve COVID-19 patients with anterior circulation large vessel occlusion and early brain imaging were included during the study period and compared with 34 control patients with anterior circulation large vessel occlusion and early brain imaging in 2019. Patients in the COVID-19 group were younger (=0.032) and had a history of diabetes mellitus more frequently (=0.039). Patients did not significantly differ on initial National Institutes of Health Stroke Scale nor time from onset to imaging (=0.18 and =0.6, respectively). Patients with COVID-19 had more severe strokes than patients without COVID-19, with a significantly lower clot burden score (median: 6.5 versus 8, =0.016), higher rate of multivessel occlusion (50% versus 8.8%, =0.005), lower DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Scores; median: 5 versus 8, =0.006), and higher infarct core volume (median: 58 versus 6 mL, =0.004). Successful recanalization rate was similar in both groups (=0.767). In-hospital mortality was higher in the COVID-19 patients' group (41.7% versus 11.8%, =0.025).

Conclusions: Early brain imaging showed higher severity large vessel occlusion strokes in patients with COVID-19. Given the massive number of infected patients, concerns should be raised about the coming neurovascular impact of the pandemic worldwide.
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http://dx.doi.org/10.1161/STROKEAHA.120.031011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446979PMC
November 2020

DNA Content in Ischemic Stroke Thrombi Can Help Identify Cardioembolic Strokes Among Strokes of Undetermined Cause.

Stroke 2020 09 19;51(9):2810-2816. Epub 2020 Aug 19.

Univ de Paris, Laboratory of Vascular Translational Science, U1148 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France (L.D.M., J.-P.D., M.S., V.O., S.D., C.D., B.H.-T.-N., M.M.).

Background And Purpose: Identification of acute ischemic stroke (AIS) cause is crucial for guidance of secondary prevention. Previous studies have yielded inconsistent results regarding possible correlations between AIS cause and thrombus composition, as assessed by semiquantitative histological analysis. Here, we performed a correlation analysis between AIS cause and AIS thrombus cellular composition and content, as assessed using quantitative biochemical assays.

Methods: Homogenates of 250 patients with AIS thrombi were prepared by mechanical grinding. Platelet, red blood cell, and leukocyte content of AIS thrombi were estimated by quantification of GP (glycoprotein) VI, heme, and DNA in thrombus homogenates. AIS cause was defined as cardioembolic, noncardioembolic, or embolic stroke of undetermined source, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment).

Results: Cardioembolic thrombi were richer in DNA (35.8 versus 13.8 ng/mg, <0.001) and poorer in GPVI (0.104 versus 0.117 ng/mg, =0.045) than noncardioembolic ones. The area under the receiver operating characteristic curve of DNA content to discriminate cardioembolic thrombi from noncardioembolic was 0.72 (95% CI, 0.63-0.81). With a threshold of 44.7 ng DNA/mg thrombus, 47% of thrombi from undetermined cause would be classified as cardioembolic with a specificity of 90%.

Conclusions: Thrombus DNA content may provide an accurate biomarker for identification of cardioembolic thrombi in patients with AIS with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03268668.
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http://dx.doi.org/10.1161/STROKEAHA.120.029134DOI Listing
September 2020

Visual Field Defect Before and After Endovascular Treatment of Occipital Arteriovenous Malformations.

Neurosurgery 2020 Jul 6. Epub 2020 Jul 6.

Interventional Neuroradiology Department, Fondation Rothschild Hospital, Paris, France.

Background: Occipital arteriovenous malformations (AVMs) carry a high risk of postoperative morbidity because of their anatomic relation to the visual cortex and optic radiations. Data regarding endovascular management of these lesions are scant.

Objective: To report our single-center experience with occipital AVMs, most of which were treated endovascularly, with a special interest for postoperative visual impairment.

Methods: From a prospective database, we assessed the clinical and radiological data of all patients with an occipital AVM managed between 1997 and 2018. The extension of the nidus to the primary visual cortex was assessed and correlated to the pre- and postintervention visual symptomatology. Modified Rankin Scale and visual fields (VFs) were assessed pre- and post-treatment and at the last follow-up.

Results: A total of 83 patients (47 males [56.6%]) with an occipital AVM were included in the study. Mean age at presentation was 33.5 ± 15.0 yr (min-max = 7-76). A total of 34 patients (41%) presented with hemorrhage related to the AVM. A total of 57 patients (68.7%) underwent endovascular treatment (EVT) alone, 20 (24.1%) underwent embolization and surgery, 3 (3.6%) underwent embolization and radiosurgery, and 3 (3.6%) were conservatively managed. A complete obliteration of the AVM was achieved in 53 patients (66.3%). A post-treatment worsening of the VF was found in 24 of the treated patients (30%), 3 patients (9%) for ruptured AVMs, and in 21 patients (46%) for unruptured AVMs. Morbidity rate was 3.7% and mortality rate was 2.5%.

Conclusion: EVT of occipital AVM carries a non-negligible rate of complications, especially regarding visual functions.
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http://dx.doi.org/10.1093/neuros/nyaa280DOI Listing
July 2020

Recent advances in devices for mechanical thrombectomy.

Expert Rev Med Devices 2020 Jul 25;17(7):697-706. Epub 2020 Jun 25.

Interventional Neuroradiology Department, Fondation Rothschild Hospital , Paris, France.

Introduction: Acute ischemic stroke (AIS) secondary to the occlusion of a large intracranial vessel (LVO) is a recognized public health problem. Mechanical thrombectomy (MT) has gained full acceptance: Class A, Level 1 in 2015 after the publication of numerous trials. Further meta-analyses have scrutinized extensively those results and international recommendations and guidelines have been given. Nevertheless, multiple-specific points remain to be clarified and are or will be under investigations.

Areas Covered: This review of the most recent literature (mostly publications after 2015) will cover the actual common practice for MT, especially focusing on the devices available (and their validation), how they are commonly used, relate the most relevant results, and detail some emerging technologies.

Expert Opinion: The authors will express their own view on the current practice and emphasize on the areas where questions remain and hypothesize what specific improvements are necessary and prone to occur.
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http://dx.doi.org/10.1080/17434440.2020.1784004DOI Listing
July 2020

Direct aspiration stroke thrombectomy: a comprehensive review.

J Neurointerv Surg 2020 Nov 12;12(11):1099-1106. Epub 2020 Jun 12.

Interventional Neuroradiology, Fondation Ophtalmologique Adolphe de Rothschild, Paris, Île-de-France, France

Mechanical thrombectomy is now the standard of care for acute ischemic stroke patients with large vessel occlusions, and can be performed with several devices and techniques. One of these techniques, direct aspiration (DA), consists of navigating a large-bore catheter up to the face of the clot and initiating forceful suction. This comprehensive review has three objectives: (1) to describe the direct aspiration technique; (2) to present the available evidence regarding predictive factors of DA success and performance compared with other techniques; and (3) to discuss the forthcoming improvements in distal aspiration.
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http://dx.doi.org/10.1136/neurintsurg-2019-015508DOI Listing
November 2020

Treatment of Acute Ischemic Stroke due to Large Vessel Occlusion With COVID-19: Experience From Paris.

Stroke 2020 08 29;51(8):2540-2543. Epub 2020 May 29.

From the Interventional Neuroradiology Department, Rothschild Foundation Hospital, Paris, France.

Background And Purpose: Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking. We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19.

Methods: All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included. Baseline clinical and radiological findings, treatment, and short-term outcomes are reported.

Results: We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO. Eight were men, with a median age of 59.5 years. Seven had none or mild symptoms of COVID-19 at stroke onset. Median time from COVID-19 symptoms to stroke onset was 6 days. All patients had brain imaging within 3 hours from symptoms onset. Five patients had multi-territory LVO. Five received intravenous alteplase. All patients had mechanical thrombectomy. Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital.

Conclusions: Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19. Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19.
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http://dx.doi.org/10.1161/STROKEAHA.120.030574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282400PMC
August 2020

Protective Effect of ApoA1 (Apolipoprotein A1)-Milano in a Rat Model of Large Vessel Occlusion Stroke.

Stroke 2020 06 14;51(6):1886-1890. Epub 2020 May 14.

From the Department of neurology and stroke center, Bichat hospital, Paris, France (C.D., P.A.).

Background and Purpose- Previous experimental studies found that the infusion of human purified nascent HDL (high-density lipoprotein) significantly reduced infarct volume and hemorrhagic transformation rate by decreasing neutrophil recruitment. ApoA1-M (apolipoprotein A1-Milano) is a natural variant of human ApoA1 that confers protection against atherosclerosis. Recombinant ApoA1-M has been formulated as a complex with phospholipids to mimic the properties of nascent HDL. The aim of this study was to assess the impact of intravenous ApoA1-M in a transient middle cerebral artery occlusion stroke model in rats. Methods- In a first experiment, rats were subjected to 120-minute transient middle cerebral artery occlusion and intravenous ApoA1-M was infused immediately or 4 hours after occlusion. In a second experiment, rats were subjected to 240-minute transient middle cerebral artery occlusion and intravenous ApoA1-M was infused with or without recombinant tPA (tissue-type plasminogen activator) immediately after recanalization. Primary outcome criteria were the infarct volume and hemorrhagic transformation rate measured at 24 hours. Platelets, coagulation, and neutrophil activation biomarkers were measured in brain homogenates and plasma. Additional in vitro experiments studied the effects of ApoA1-M on platelet aggregation and platelet-neutrophil interactions. Results- The infusion of ApoA1-M immediately or 4 hours after 120-minute transient middle cerebral artery occlusion significantly reduced the infarct volume compared with saline (=0.034 and =0.036, respectively). Compared with tPA alone, co-administration of ApoA1-M and tPA showed similar rates of hemorrhagic transformation. ApoA1-M had no significant inhibition effect on neutrophil activation biomarkers. Platelet activation was slightly decreased in rats treated with ApoA1-M compared with saline. In vitro, the incubation of human and rat platelet-rich plasma with ApoA1-M significantly reduced ADP-induced platelet aggregation (=0.001 and =0.02, respectively). Conclusions- ApoA1-Milano significantly decreased the infarct volume through an inhibition of platelet aggregation but did not reduce hemorrhagic transformation and neutrophils activation as expected after previous experimental studies with nascent HDL. Visual Overview- An online visual overview is available for this article.
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http://dx.doi.org/10.1161/STROKEAHA.119.027898DOI Listing
June 2020

Identifying the predictors of first-pass effect and its influence on clinical outcome in the setting of endovascular thrombectomy for acute ischemic stroke: Results from a multicentric prospective registry.

Int J Stroke 2021 Jan 7;16(1):20-28. Epub 2020 May 7.

0Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Nantes, Nantes, France.

Background: The first-pass effect, defined as a complete or near-complete recanalization after one pass (first-pass effect) of a mechanical thrombectomy device, has been related to better clinical outcome than good recanalization after more than one pass in acute ischemic stroke. We searched for predictors of first-pass effect by analyzing the results within a large prospective multicentric registry.

Methods: We included patients treated by mechanical thrombectomy for isolated anterior intracranial occlusions. A multi-variate logistic regression analysis was carried out to search for predictors of first-pass effect. We also analyzed the percentage of patients with 90-day modified Rankin Scale score 0 to 2, excellent outcome (90-day modified Rankin Scale 0 to 1), 24-h NIHSS change, and 90-day all-cause mortality.

Results: Among the 1832 patients included, clinical outcome at 90 days was significantly better in first-pass effect patients (50.6% vs. 38.9% in patients without first-pass effect), with a center-adjusted OR associated with first-pass effect of 1.74 (95%CI, 1.24 to 1.77). Older age, a lower systolic blood pressure, an MCA-M1 occlusion, higher DWI-ASPECTS at admission, mechanical thrombectomy under local anesthesia, and combined first-line device strategy were independent predictors of first-pass effect.

Conclusions: In this study, a strategy combining thrombectomy and thrombo-aspiration was more effective than other strategies in achieving first-pass effect. In addition, we confirm that clinical outcome was better in patients with first-pass effect compared to non-first-pass effect patients.
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http://dx.doi.org/10.1177/1747493020923051DOI Listing
January 2021

Effect of Steady and Dynamic Blood Pressure Parameters During Thrombectomy According to the Collateral Status.

Stroke 2020 04 11;51(4):1199-1206. Epub 2020 Mar 11.

From the Interventional Neuroradiology Department, Fondation Rothschild, Paris, France (B.M., J.-P.D., W.B., R.F., H.R., S.S., G.C., S.E., R.B., M.P., M.M.).

Background and Purpose- Guidelines regarding blood pressure (BP) management during endovascular therapy (EVT) for anterior circulation strokes are questionable since the optimal BP target is a matter of debate. To evaluate the importance of hemodynamic control during EVT, we investigated the impact of dynamic and steady BP parameters during EVT on functional outcome (part 1) and according to the collateral status (CS; part 2). Methods- We performed a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Recanalization). BP was measured noninvasively during EVT and CS assessed on the angiographic run before EVT. We studied dynamic BP parameter using BP variability (coefficient of variation) and steady BP parameter (hypotension time defined as systolic BP <140 mm Hg and mean arterial pressure <90 mm Hg). The primary outcome was favorable outcome defined as a 3-month modified Rankin Scale score between 0 and 2. Results- Among the 381 patients of the ASTER study, 172 patients were included in part 1 and 159 in part 2. Systolic BP, diastolic BP, and mean arterial pressure variability were negatively associated with favorable outcome regardless of CS: per 10-unit increase, adjusted odds ratios were 0.45 (95% CI, 0.20-0.98), 0.37 (95% CI, 0.19-0.72), and 0.35 (95% CI, 0.16-0.76), respectively. According to CS, the hypotension time with periprocedural mean arterial pressure <90 mm Hg was negatively associated with favorable outcome in patients with poor CS (adjusted odds ratio, 0.88 [95% CI, 0.72-1.09]) but not in patients with good CS (adjusted odds ratio, 1.24 [95% CI, 0.91-1.67]; =0.047). Conclusions- The CS did not modify the association between dynamic parameters and functional outcomes, but some findings suggest that the CS modifies the association between steady parameter and functional outcomes. Hypotension time according to the CS was not statistically predictive of poor outcomes but displayed a trend toward worse outcomes for patients with poor CS only.
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http://dx.doi.org/10.1161/STROKEAHA.119.026769DOI Listing
April 2020

Could we apply the criteria of DAWN and DEFUSE-3 trials for slow progressors, beyond 24 h?

Acta Neurol Belg 2020 08 18;120(4):977-980. Epub 2020 Jan 18.

Interventional Neuroradiology Department, Fondation Ophtalmologique Adolphe de Rothschild, Rue Manin 25, 75019, Paris, France.

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http://dx.doi.org/10.1007/s13760-020-01277-7DOI Listing
August 2020

Presence of direct vertebrobasilar perforator feeders in posterior fossa arteriovenous malformations and association with poor outcomes after endovascular treatment.

J Neurosurg 2019 Nov 8:1-9. Epub 2019 Nov 8.

1Department of Interventional Neuroradiology, Fondation Rothschild Hospital, Paris, France; and.

Objective: Treatment of posterior fossa arteriovenous malformations (PFAVMs) remains controversial as it is always challenging and may lead to major complications. Nonetheless, these lesions are more likely to bleed and generate poorer outcomes than other brain AVMs. The aim of this study was to evaluate the effect of endovascular treatment on long-term outcomes and identify the patient subgroups that might benefit from endovascular treatment.

Methods: The authors performed a retrospective analysis of all consecutive cases of PFAVM managed at the Fondation Rothschild Hospital between 1995 and 2018. Clinical, imaging, and treatment data were prospectively gathered; these data were analyzed with respect to long-term outcomes.

Results: Among the 1311 patients with brain AVMs, 114 (8.7%) had a PFAVM, and 88 (77.2%) of these patients had a history of bleeding. Of the 114 PFAVMs, 101 (88.6%) were treated (83 ruptured and 18 unruptured). The mean duration of follow-up was 47.6 months (range 0-240 months). Good neurological outcome at last follow-up was achieved in 79 cases (78.2%). Follow-up angiography showed obliteration of the PFAVM in 68.3% of treated cases. The presence of direct vertebrobasilar perforator feeders was associated with neurological deterioration (OR 5.63, 95% CI 11.15-30.76) and a lower obliteration rate (OR 15.69, 95% CI 2.52-304.03) after endovascular treatment. Other predictors of neurological deterioration and obliteration rate were consistent with the Spetzler-Martin grading system.

Conclusions: Advances in endovascular techniques have enabled higher obliteration rates in the treatment of PFAVMs, but complication rates are still high. Subgroups of patients who might benefit from treatment must be carefully selected and the presence of direct vertebrobasilar perforator feeders must call into question the indication for endovascular treatment.
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http://dx.doi.org/10.3171/2019.8.JNS191971DOI Listing
November 2019

Predictors of Parenchymal Hematoma After Mechanical Thrombectomy: A Multicenter Study

Stroke 2019 09 22;50(9):2364-2370. Epub 2019 Jul 22.

Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France (W.B., R.F., J.-P.D., K.Z., B.M., H.R., G.C., S.S., S.E., M.M., M.P., R.B.).

Background And Purpose: Parenchymal hematoma (PH) is a rare but dreadful complication of acute ischemic stroke with unclear underlying mechanisms. We aimed to study the incidence and predictors of PH after mechanical thrombectomy.

Methods: Data from a prospective observational multicenter registry was screened to identify acute ischemic stroke patients with an anterior circulation large vessel occlusion who underwent mechanical thrombectomy. Clinical, imaging, and procedural characteristics were used for the analysis, including brain imaging systematically performed at 24 hours. PH occurrence was assessed according to ECASS (European Collaborative Acute Stroke Study) criteria. Univariate and multivariable analyses were performed to identify predictors of PH.

Results: A total of 1316 patients were included in the study. PH occurred in 153 out of 1316 patients (11.6%) and was associated with a lower rate of favorable outcome and increased mortality. On multivariable analysis, age (per 1 year increase, odds ratio [OR], 1.01; 95% CI, 1.00–1.03; P=0.05), current smoking (OR, 2.02; 95% CI, 1.32–3.09; P<0.01), admission Alberta Stroke Program Early CT Score (per a decrease of 1 point, OR, 1.70; 95% CI, 1.18–2.44; P<0.01), general anesthesia (OR, 1.98; 95% CI, 1.36–2.90; P<0.001), angiographic poor collaterals (OR, 2.13; 95% CI, 1.36–3.33; P<0.001) and embolization in new territory (OR, 2.94; 95% CI, 1.70–5.10; P<0.001) were identified as independent predictors of PH.

Conclusions: PH occurred at a rate of 11.6% after mechanical thrombectomy, with high morbidity and mortality. Our study identified clinical, radiological, and procedural predictors of PH occurrence that can serve as the focus of future periprocedural management studies with the aim of reducing its occurrence.
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http://dx.doi.org/10.1161/STROKEAHA.118.024512DOI Listing
September 2019

Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis.

Neurology 2019 10 20;93(18):e1686-e1698. Epub 2019 Sep 20.

From U1148 Institut National de la Santé et de la Recherche Médicale (INSERM) (L.D.M., J.-P.D., V.O., M.S.N., S.D.M., C.D., S.L., M.-C.B., J.-B.M., M.J.-P., B.H.-T.-N., M.M.), Laboratory of Vascular Translational Science, Sorbonne Paris Cité, Université Paris Diderot; Department of Interventional Neuroradiology (J.-P.D., R.B., M.P., M.M.), Rothschild Foundation Hospital, Paris; and Toulouse University Medical Center (J.-M.O.), France.

Objectives: Thrombi responsible for large vessel occlusion (LVO) in the setting of acute ischemic stroke (AIS) are characterized by a low recanalization rate after IV thrombolysis. To test whether AIS thrombi have inherent common features that limit their susceptibility to thrombolysis, we analyzed the composition and ultrastructural organization of AIS thrombi causing LVO.

Methods: A total of 199 endovascular thrombectomy-retrieved thrombi were analyzed by immunohistology and scanning electron microscopy (SEM) and subjected to ex vivo thrombolysis assay. The relationship between thrombus organization and thrombolysis resistance was further investigated in vitro using thrombus produced by recalcification of citrated whole blood.

Results: SEM and immunohistology analyses revealed that, although AIS thrombus composition and organization was highly heterogeneous, AIS thrombi shared a common remarkable structural feature in the form of an outer shell made of densely compacted thrombus components including fibrin, von Willebrand factor, and aggregated platelets. In vitro thrombosis experiments using human blood indicated that platelets were essential to the formation of the thrombus outer shell. Finally, in both AIS and in vitro thrombi the thrombus outer shell showed a decreased susceptibility to tissue plasminogen activator-mediated thrombolysis as compared to the thrombus inner core.

Interpretation: Irrespective of their etiology and despite their heterogeneity, intracranial thrombi causing LVO have a core shell structure that influences their susceptibility to thrombolysis.
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http://dx.doi.org/10.1212/WNL.0000000000008395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946479PMC
October 2019