Publications by authors named "Lucie Cabrejo"

32 Publications

Evaluation of non-stenotic carotid atherosclerotic plaques with combined FDG-PET imaging and CT angiography in patients with ischemic stroke of unknown origin.

J Nucl Cardiol 2021 Jan 18. Epub 2021 Jan 18.

Department of Nuclear Medicine, Georges-Pompidou European Hospital, DMU IMAGINA, Assistance Publique-Hôpitaux de Paris, University of Paris, 20 rue Leblanc, 75015, Paris, France.

Objectives: Non-stenotic plaques are an underestimated cause of ischemic stroke. Imaging aspects of high-risk carotid plaques can be identified on CT angiography (CTA) and 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) imaging. We evaluated in patients with cryptogenic ischemic stroke the usefulness of FDG-PET-CTA.

Methods: 44 patients imaged with CTA and FDG-PET were identified retrospectively. Morphological features were identified on CTA. Intensity of FDG uptake in carotid arteries was quantified on PET.

Results: Patients were imaged 7 ± 8 days after stroke. 44 non-stenotic plaques with increased 18F-FDG uptake were identified in the carotid artery ipsilateral to stroke and 7 contralateral. Most-diseased-segment TBR on FDG-PET was higher in artery ipsilateral vs. contralateral to stroke (2.24 ± 0.80 vs. 1.84 ± 0.50; p < .05). In the carotid region with high FDG uptake, prevalence of hypodense plaques and extent of hypodensity on CTA were higher in artery ipsilateral vs. contralateral to stroke (41% vs. 11%; 0.72 ± 1.2 mm vs. 0.13 ± 0.43 mm; p < .05).

Conclusions: In patients with ischemic stroke of unknown origin and non-stenotic plaques, we found an increased prevalence of high-risk plaques features ipsilateral vs. contralateral to stroke on FDG-PET-CTA imaging suggesting a causal role for these plaques.
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http://dx.doi.org/10.1007/s12350-020-02511-8DOI Listing
January 2021

Prevalence and Outcome of Potential Candidates for Left Atrial Appendage Closure After Stroke With Atrial Fibrillation: WATCH-AF Registry.

Stroke 2020 08 9;51(8):2355-2363. Epub 2020 Jul 9.

APHP, Department of Neurology and Stroke center, Bichat Hospital, INSERM LVTS-U1148, DHU FIRE, Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France (E.O., E.M., C.G., C.H., P.C.L., H.C., L.C., A.M.-B., R.R., P.A.).

Background And Purpose: As a result of contraindications (eg, frailty, cognitive impairment, comorbidities) or patient refusal, many patients with stroke and atrial fibrillation cannot be discharged on oral anticoagulant. Among them, the proportion of potential candidates for left atrial appendage closure (LAAC) and their 12-month outcome is not well known.

Methods: The prospective WATCH-AF registry (Warfarin Aspirin Ten-A Inhibitors and Cerebral Infarction and Hemorrhage and Atrial Fibrillation) enrolled consecutive patients admitted within 72 hours of an acute stroke associated with atrial fibrillation in 2 stroke centers. Scales to evaluate stroke severity, disability, functional independence, risk of fall, cognition, ischemic and hemorrhagic risk-stratification, and comorbidities were systematically collected at admission, discharge, 3, 12 months poststroke. The 2 main end points were death or dependency (modified Rankin Scale score >3) and recurrent stroke (brain infarction and brain hemorrhage).

Results: Among 400 enrolled patients (370 with brain infarction, 30 with brain hemorrhage), 31 died before discharge and 57 (14.3%) were possible European Heart Rhythm Association/European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Rhythm Society candidates for LAAC. At 12 months, the rate of death or dependency was 17.9%, and the rate of stroke recurrence was 9.8% in the 274/400 (68.5%) patients discharged on a long-term oral anticoagulant strategy, as compared with 17.5% and 24.7%, respectively, in 57 patients candidate for LAAC. As compared with patients on a long-term oral anticoagulant strategy, there was a 2-fold increase in the risk of stroke recurrence in the group with an indication for LAAC (adjusted hazard ratio, 2.58 [95% CI, 1.40-4.76]; P=0.002).

Conclusions: Fourteen percent of patients with stroke associated with atrial fibrillation were potential candidates for LAAC. The 12-month stroke risk of these candidates was 3-fold the risk of anticoagulated patients.
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http://dx.doi.org/10.1161/STROKEAHA.120.029267DOI Listing
August 2020

Twelve-month outcome in patients with stroke and atrial fibrillation not suitable to oral anticoagulant strategy: the WATCH-AF registry.

Open Heart 2019;6(2):e001187. Epub 2019 Dec 2.

Department of Neurology and Stroke center, Paris Univesity, Paris, France.

Aims: Long-term oral anticoagulant (LTOAC) reduces ischaemic stroke recurrences. Because of bleeding history, frailty, cognitive impairment, comorbidities or patient refusal, many cannot be discharged from stroke unit on LTOAC. Proportion and outcome of these patients is not well known.

Methods: The Warfarin Aspirin Ten-a inhibitor Cerebral infarction and Haemorrhage and atrial fibrillation (AF) prospective registry enrolled consecutive patients with an acute stroke associated with AF. Scales to evaluate stroke severity, disability, functional independence, cognition, risk of fall, ischaemic and haemorrhagic risk stratification were systematically collected at admission, discharge, 3 and 12 months poststroke. The two main 12-month endpoints were death or dependency (modified Rankin Scale >3) and recurrent stroke.

Results: Among 400 patients (370 brain infarctions, 30 brain haemorrhages), 274 were discharged on LTOAC, 31 died before discharge and 95 (24%) were not discharge on anticoagulant (frailty, bedridden or demented, EHRA/ESC contraindication to anticoagulant). Death or dependency and recurrent stroke occurred in 19.8% and 9.9%, respectively, in patient on anticoagulant, and 33.5% and 27.2% in those not on anticoagulant (both p<0.001). Patient not anticoagulated at discharge had a 1.6-fold increase in the risk of death or dependency at 12 months (HR 1.65; 95% CI 1.05 to 2.61; p=0.032) and a 2.5-fold increase in the risk of stroke (HR 2.46; 95% CI 1.36 to 4.44; p=0.003).

Conclusions: One-fourth of patients with stroke associated with AF are not discharged on anticoagulation and have a dramatic increase in the risk of death or dependency at 12 months as well as recurrent stroke. Alternative treatments should be trialled in these patients.
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http://dx.doi.org/10.1136/openhrt-2019-001187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927512PMC
February 2021

A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

N Engl J Med 2020 01 18;382(1). Epub 2019 Nov 18.

From the Department of Neurology and Stroke Center (P.A., J.L., H.C., L.C., C.G., C.H., P.C.L., E.M., P.-J.T.) and the Department of Cardiology (J.A., G.D., P.G.S.), Assistance Publique-Hôpitaux de Paris (APHP), Bichat Hospital, Laboratory for Vascular Translational Science, INSERM Unité 1148, Département Hospitalo Universitaire-Fibrose Inflammation Remodelage, and the Department of Cardiology, Cochin Hospital (O.V.), University of Paris, the Department of Neurology, Foch Hospital (B.L.), Urgences Cerebrovasculaires (Y.S.), Centre de Pharmacoépidémiologie de l'APHP (N.Y.), and the Department of Endocrinology (E.B.), Hôpital de la Pitié-Salpêtrière, the Department of Biostatistics, APHP, Université Paris Diderot, Sorbonne Paris Cité, Fernand Widal Hospital (É.V.), and the Department of Endocrinology, Sorbonne University (E.B.), Paris, Équipe d'Accueil EA2694, Santé Publique: Epidémiologie et Qualité des Soins (J.L.), and the Department of Neurology, Stroke Unit, University of Lille, Centre Hospitalier Universitaire (CHU) de Lille (D.L.), Lille, the Department of Neurology, University Hospital of Dijon, University of Burgundy, Dijon (Y.B., M.G.), the Stroke Unit, Pasteur Hospital, Nice (M.-H.M.), Hospices Civils de Lyon, Department of Neurology and Stroke Center, Lyon University, Lyon (N.N.), the Department of Neurology, Versailles University Hospital, Versailles (F.P.), the Department of Vascular Neurology, Pellegrin Tripode Hospital, University of Bordeaux, Bordeaux (I.S.), and the Department of Neurology, Université Caen Normandie, CHU Caen Normandie, INSERM Unité 1237, Cyceron, Caen (E.T.) - all in France; Asan Medical Center (J.S.K.), the Department of Neurology, Eunpyeong St. Mary's Hospital, Catholic University of Korea (Y.-J.K.), and the Department of Neurology, Soonchunhyang University College of Medicine (K.-B.L.), Seoul, Dong-a University Hospital (J.-K.C.) and the Department of Neurology and Stroke Center, Pusan National University Hospital (S.M.S.), Busan, and the Department of Neurology, Hallym University Sacred Heart Hospital, Anyang (B.-C.L.) - all in South Korea; and the National Heart and Lung Institute-Imperial College and the Institute of Cardiovascular Medicine and Science-Royal Brompton Hospital, London (P.G.S.).

Background: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.

Methods: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes.

Results: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.

Conclusions: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).
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http://dx.doi.org/10.1056/NEJMoa1910355DOI Listing
January 2020

Fatal Aβ cerebral amyloid angiopathy 4 decades after a dural graft at the age of 2 years.

Acta Neuropathol 2018 05 5;135(5):801-803. Epub 2018 Mar 5.

Département de Neuropathologie Raymond Escourolle, GH Pitié-Salpêtrière, Faculté de médecine Sorbonne Université, Paris, France.

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http://dx.doi.org/10.1007/s00401-018-1828-9DOI Listing
May 2018

Prevalence of Systemic Atherosclerosis Burdens and Overlapping Stroke Etiologies and Their Associations With Long-term Vascular Prognosis in Stroke With Intracranial Atherosclerotic Disease.

JAMA Neurol 2018 02;75(2):203-211

Institut National de la Santé Et de la Recherche Médicale, Laboratory for Vascular Translational Sciences 1148 and Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France.

Importance: Patients who have experienced stroke with intracranial atherosclerotic disease (ICAD) may also have concomitant atherosclerosis in different arterial beds and other possible causes for ischemic stroke. However, little is known about the frequency and prognostic effect of such overlapping diseases.

Objectives: To describe the prevalence of systemic atherosclerotic burdens and overlapping stroke etiologies and their contributions to long-term prognoses among patients who have experienced stroke with ICAD.

Design, Setting, And Participants: The Asymptomatic Myocardial Ischemia in Stroke and Atherosclerotic Disease study is a single-center prospective study in which 405 patients with acute ischemic stroke within 10 days of onset were consecutively enrolled between June 2005 and December 2008 and followed up for 4 years. After excluding 2 patients because of incomplete investigations, 403 were included in this analysis.

Main Outcomes And Measures: Significant ICAD was defined as having 50% or greater stenosis/occlusion by contrast-enhanced/time-of-flight magnetic resonance angiography, computed tomography angiography, and/or transcranial Doppler ultrasonography. Systemic vascular investigations on atherosclerotic disease were performed with ultrasonography in carotid arteries, aorta and femoral arteries, and by angiography in coronary arteries. Coexistent stroke etiologies were assessed using the atherosclerosis, small-vessel disease, cardiac pathology, other cause, and dissection (ASCOD) grading system. We estimated the 4-year risk of major adverse cardiovascular events (MACE), including vascular death, nonfatal cardiac events, nonfatal stroke, and major peripheral arterial events.

Results: Of 403 participants, 298 (74%) were men and the mean (SD) age was 62.6 (13.1) years. Significant ICAD was found in 146 (36.2%). Patients with significant ICAD more often had aortic arch (70 [60.9%] vs 99 [49.0%]; P = .04) and coronary artery (103 [76.9%] vs 153 [63.2%]; P = .007) atherosclerosis than those without. Among patients with ICAD, concurrent stenosis in the extracranial carotid artery (24 [23.4%] vs 3 [9.0%]; P = .08; adjusted hazard ratio[aHR] = 2.12) and the coronary artery (19 [29.9%] vs 8 [12.8%]; P = .01; aHR = 1.90) increased the MACE risk. Furthermore, patients with ICAD who also had any cardiac pathology (ASCOD grade C1-3) were at a higher MACE risk than others (grade C0) (20 [28.2%] vs 7 [11.4%]; P = .01; aHR = 2.24). By contrast, patients with ICAD with any form of small vessel disease (grade S1-3) had a lower MACE risk than those without (grade S0) (20 [17.3%] vs 6 [34.6%]; P = .05; aHR = 0.23).

Conclusions And Relevance: Patients with ICAD often have coexisting systemic atherosclerosis and multiple potential stroke mechanisms that affect their prognosis, suggesting that extensive evaluations of overlapping diseases may allow better risk stratification.
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http://dx.doi.org/10.1001/jamaneurol.2017.3960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838618PMC
February 2018

Clinical Significance of Isolated Atypical Transient Symptoms in a Cohort With Transient Ischemic Attack.

Stroke 2017 06 9;48(6):1495-1500. Epub 2017 May 9.

From the INSERM U 1148 and Paris-Diderot University, Sorbonne Paris Cité, France (P.C.L., L.S., J.L., E.M., L.C., C.G., I.F.K., P.-J.T., P.A.); and Department of Neurology and Stroke Centre (P.C.L., L.S., E.M., L.C., C.G., P.-J.T., P.A.) and Department of Radiology (I.F.K.), Bichat University Hospital, Paris, France.

Background And Purpose: Contrary to typical transient symptoms (TS), atypical TS, such as partial sensory deficit, dysarthria, vertigo/unsteadiness, unusual cortical visual deficit, and diplopia, are not usually classified as symptoms of transient ischemic attack when they occur in isolation, and their clinical relevance is frequently denied.

Methods: Consecutive patients with recent TS admitted in our transient ischemic attack clinic (2003-2008) had systematic brain, arterial, and cardiac investigations. We compared the prevalence of recent infarction on brain imaging, major investigational findings (symptomatic intracranial or extracranial atherosclerotic stenosis ≥50%, cervical arterial dissection, and major source of cardiac embolism), and 1-year risk of major vascular events in patients with isolated typical or atypical TS and nonisolated TS, after exclusion of the main differential diagnoses.

Results: Among 1850 patients with possible or definite ischemic diagnoses, 798 (43.1%) had isolated TS: 621 (33.6%) typical and 177 (9.6%) atypical. Acute infarction on brain imaging was similar in patients with isolated atypical and typical TS but less frequent than in patients with nonisolated TS, observed in 10.0%, 11.5%, and 15.3%, respectively (<0.0001). Major investigational findings were found in 18.1%, 26.4%, and 26.3%, respectively (=0.06). One-year risk of a major vascular events was not significantly different in the 3 groups.

Conclusions: Transient ischemic attack diagnosis should be considered and investigated in patients with isolated atypical TS.
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http://dx.doi.org/10.1161/STROKEAHA.117.016743DOI Listing
June 2017

Outcomes after stroke thrombolysis according to prior antiplatelet use.

Int J Stroke 2015 Feb 8;10(2):163-9. Epub 2014 Dec 8.

Department of Neurology and Stroke Centre, Bichat University Hospital, Paris, France; Laboratory of Vascular Translational Science, INSERM 1148 and Paris-Diderot University, Paris, France.

Background: Thirty percent of ischemic stroke (IS) patients suffering from acute stroke are under antiplatelet therapy.

Aims: We evaluated whether prior antiplatelet use before intravenous (IV), intra-arterial (IA) or combined IV/IA therapy may be associated with worse outcomes and an increased intracerebral hemorrhage (ICH) risk after reperfusion therapies.

Methods: We analyzed data from our patient registry (n = 874) and conducted a systematic review of previous observational studies. The primary outcome was the percentage of patients who developed symptomatic ICH (sICH), defined in our registry per ECASS-II definition.

Results: We identified 43 previous reports that evaluated the impact of prior antiplatelet use on outcomes after reperfusion therapy in AIS patients. Prior antiplatelet use was found in 35% of AIS patients, eligible for reperfusion therapies and was associated with a worse vascular profile. In an unadjusted meta-analysis that included our registry data, prior antiplatelet use was associated with more sICH per ECASS-II definition (OR, 1.78 (95% CI, 1.48-2.13), and less favorable outcome (OR, 0.86; 95% CI, 0.77-0.98). However, in multivariate analyses conducted in our registry showed that prior antiplatelet use was not associated with worse outcome (P > 0.23); and in the systematic review, only 3 studies reported a slight, but significant adjusted increase in sICH risk, of whom one had conflicting results according to sICH definition.

Conclusions: These results suggest no significant detrimental effect of prior antiplatelet use in AIS patients treated by IV, IA or combined IV/IA therapy. Further studies are needed to assess the specific impact of different and cumulative antiplatelet agents.
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http://dx.doi.org/10.1111/ijs.12421DOI Listing
February 2015

The smoking paradox: impact of smoking on recanalization in the setting of intra-arterial thrombolysis.

Cerebrovasc Dis Extra 2014 Jan 1;4(2):84-91. Epub 2014 May 1.

Department of Neurology and Stroke Centre, Paris, France ; INSERM U-698 and Paris-Diderot University, Paris, France.

Background: The smoking paradox refers to a better outcome in smokers eligible for thrombolytic treatment in myocardial infarction or ischemic stroke. Recent findings suggest that current smokers may present higher recanalization rates after intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA). We evaluated the impact of smoking in a consecutive series of patients treated with intra-arterial (IA) rt-PA.

Methods: We analyzed data collected between April 2007 and December 2012 in our prospective registry. All acute ischemic stroke patients with an arterial occlusion treated by IA rt-PA (± IV, ± thrombectomy) were included. Arterial status was monitored with conventional angiography during the IA procedure. The primary study outcome was a complete recanalization achieved immediately after termination of IA rt-PA infusion. Secondary outcomes included complete recanalization after the end of the endovascular therapy (including complete recanalization achieved after adjunctive thrombectomy), favorable outcome (90-day modified Rankin Score ≤2), 90-day all-cause mortality, and any intracerebral hemorrhage.

Results: Among the 227 included patients, 18.5% (n = 42) were current smokers and 16.7% (n = 38) former smokers. Compared with nonsmokers, current smokers were younger, more often men, had less frequently hypertension, and cardioembolic etiology, whereas former smokers were more often men and had more frequently hypercholesterolemia. The rate of complete recanalization was 30% (n = 68) after IA rt-PA infusion and 49% after adjunctive thrombectomy. A higher complete recanalization rate was found both in current smokers (45.2%) and former smokers (42.1%) compared to nonsmokers (22.5%). After adjustment for potential confounders, the adjusted odds ratio (OR) for complete recanalization associated with ever-smokers was 2.51 [95% confidence interval (CI) 1.26-4.99; p = 0.009]. A similar adjusted OR was found when the complete recanalization achieved after thrombectomy was included (OR 2.18, 95% CI 1.13-4.19; p = 0.019). However, smoking status was not independently associated with favorable outcome (adjusted OR 1.41, 95% CI 0.62-3.22 for former smokers, and adjusted OR 1.35, 95% CI 0.59-3.05 for current smokers), 90-day all-cause mortality (adjusted OR 0.68, 95% CI 0.25-1.81 for former smokers, and adjusted OR 1.55, 95% CI 0.54-4.48 for current smokers) or intracerebral hemorrhage (adjusted OR 0.72, 95% CI 0.29-1.76 for former smokers, and adjusted OR 0.80, 95% CI 0.32-1.96 for current smokers).

Conclusions: IA rt-PA administration was more effective to achieve complete arterial recanalization in current as well as former smokers. The characterization of the smoking paradox pathophysiology may lead to the identification of a patient-target population with a favorable response to rt-PA therapy. However, the smoking paradox should not be misinterpreted and not be used to promote smoking.
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http://dx.doi.org/10.1159/000357218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035683PMC
January 2014

Spectrum of transient visual symptoms in a transient ischemic attack cohort.

Stroke 2013 Dec 31;44(12):3312-7. Epub 2013 Oct 31.

From INSERM U 698 and Paris-Diderot University, Sorbonne Paris Cité, Paris, France (P.C.L., L.C., J.L., M.M., E.M., C.G., I.F.K., G.S., J.G.-V., P.-J.T., P.A.); and Department of Neurology and Stroke Centre (P.C.L., L.C., M.M., E.M., C.G., H.A., B.L., J.-M.O., G.S., J.G.-V., P.-J.T., P.A.) and Department of Radiology (I.F.K.), Bichat University Hospital, Paris France.

Background And Purpose: Transient visual symptoms (TVS) are common complaints. They can be related to transient ischemic attacks, but the nature of the symptoms often remains uncertain, and data on prognosis are scarce. We studied the prevalence, presentation, and effect of different types of TVS, paying particular attention to the association with high-risk pathology of embolism.

Methods: A total of 2398 patients with suspected transient ischemic attack admitted to the SOS-TIA clinic between January 2003 and December 2008 underwent immediate evaluation and treatment.

Results: Eight hundred twenty-six (34.5%) patients had TVS, including 422 (17.6%) patients with isolated TVS. Transient monocular blindness was the most frequent TVS (36.3%), followed by diplopia (13.4%), homonymous lateral hemianopia (12.3%), bilateral positive visual phenomena (10.8%), and lone bilateral blindness (4.5%). Positive diffusion-weighted imaging was found in 11.8%, 8.1%, 8.1%, and 5.0% of patients with homonymous lateral hemianopia, diplopia, lone bilateral blindness, and transient monocular blindness, respectively. Among 1850 patients (595 patients with TVS) with definite/possible transient ischemic attack or minor stroke, a major source of embolism of cardiac or arterial origin was found less frequently in patients with isolated or nonisolated TVS than in patients without TVS (19.6%; 19.7% versus 28.1%, respectively; P<0.001). However, we found a higher rate of atrial fibrillation in patients with homonymous lateral hemianopia (23.2%) than in patients with other TVS (4.0%; adjusted odds ratio, 6.71; 95% confidence interval, 2.99-15.06) or nonvisual symptoms (9.1%; adjusted odds ratio, 4.39; 95% confidence interval, 2.26-8.50).

Conclusions: Approximately 20% of patients with TVS had a major source of embolism detected, requiring urgent management. Atrial fibrillation was particularly frequent in patients with transient homonymous lateral hemianopia.
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http://dx.doi.org/10.1161/STROKEAHA.113.002420DOI Listing
December 2013

Aortic arch atheroma in transient ischemic attack patients.

Atherosclerosis 2013 Nov 11;231(1):124-8. Epub 2013 Sep 11.

Department of Neurology and Stroke Centre, Bichat University Hospital, INSERM U-698 and Paris-Diderot University, Paris, France. Electronic address:

Objective: Aortic arch atheroma (AAA) is associated with vascular risk factors and with stroke risk. Its prevalence and prognosis remain to be defined in patients with transient ischemic attack (TIA).

Methods: Using data from the SOS-TIA registry, we assessed the prevalence of AAA detected by transesophageal echocardiography (TEE). AAA was graded as moderate (<4 mm) or severe (≥4 mm). All patients had a standardized work-up investigation and were followed for 1 year.

Results: Between January 2003 and December 2008, 1850 patients with definite/possible TIA or minor stroke were enrolled and 1231 (67%) underwent TEE. Moderate AAA was found in 26% of patients (n = 324) and severe AAA in 14% (n = 171), giving an overall AAA prevalence of 40%. Among the 873 patients without identified cause of TIA, the prevalence of moderate and severe AAA were 24% and 12% respectively. Intracranial or extracranial stenosis ≥50% were detected in 21% of patients and were independently associated with AAA (adjusted odds ratio, 1.65, 95% confidence interval (CI), 1.23-2.22). At one-year, incidence of recurrent vascular events was 2.2% in patients without AAA, 4.1% in moderate AAA and 6.6% in severe AAA (log-rank, p for trend = 0.003). Using patients without AAA as reference, and after adjustment on vascular risk factors, the hazard ratio (95% CI) for moderate was 1.36 (0.62-2.99) and 2.08 (0.89-4.86) for severe (p for trend = 0.095).

Conclusions: These findings support a systematic identification of AAA in TIA patients to optimize risk stratification in this specific population.
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http://dx.doi.org/10.1016/j.atherosclerosis.2013.08.025DOI Listing
November 2013

Overlap of diseases underlying ischemic stroke: the ASCOD phenotyping.

Stroke 2013 Sep 16;44(9):2427-33. Epub 2013 Jul 16.

Paris-Diderot University, Sorbonne Paris Cité, Paris, France.

Background And Purpose: ASCOD phenotyping (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; and D, dissection) assigns a degree of likelihood to every potential cause (1 for potentially causal, 2 for causality is uncertain, 3 for unlikely causal but disease is present, 0 for absence of disease, and 9 for insufficient workup to rule out the disease) commonly encountered in ischemic stroke. We used ASCOD to investigate the overlap of underlying vascular diseases and their prognostic implication.

Methods: A single rater applied ASCOD in 405 patients enrolled in the Asymptomatic Myocardial Ischemia in Stroke and Atherosclerotic Disease study.

Results: A was present in 90% of patients (A1=43% and A2=15%), C in 52% (C1=23% and C2=14%), and S in 66% (S1=11% and S2=2%). On the basis of grades 1 and 2, 25% of patients had multiple underlying diseases, and 80% when all 3 grades were considered. The main overlap was found between A and C; among C1 patients, A was present in 92% of cases (A1=28%, A2=20%, and A3=44%). Conversely, among A1 patients, C was present in 47% of cases (C1=15%, C2=15%, and C3=17%). Grades for C were associated with gradual increase in the 3-year risk of vascular events, whereas risks were similar across A grades, meaning that the mere presence of atherosclerotic disease qualifies for high risk, regardless the degree of likelihood for A.

Conclusions: ASCOD phenotyping shows that the large overlap among the 3 main diseases, and the high prevalence of any form of atherosclerotic disease, reinforces the need to systematically control atherosclerotic risk factors in all ischemic strokes.
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http://dx.doi.org/10.1161/STROKEAHA.113.001363DOI Listing
September 2013

Diabetes mellitus, admission glucose, and outcomes after stroke thrombolysis: a registry and systematic review.

Stroke 2013 Jul 23;44(7):1915-23. Epub 2013 May 23.

Department of Neurology and Stroke Centre, Bichat University Hospital, Paris, France.

Background And Purpose: The potential detrimental effect of diabetes mellitus and admission glucose level (AGL) on outcomes after stroke thrombolysis is unclear. We evaluated outcomes of patients treated by intravenous and/or intra-arterial therapy, according to diabetes mellitus and AGL.

Methods: We analyzed data from a patient registry (n=704) and conducted a systematic review of previous observational studies. The primary study outcome was the percentage of patients who achieved a favorable outcome (modified Rankin score ≤2 at 3 months).

Results: We identified 54 previous reports that evaluated the effect of diabetes mellitus or AGL on outcomes after thrombolysis. In an unadjusted meta-analysis that included our registry data and previous available observational data, diabetes mellitus was associated with less favorable outcome (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.73-0.79) and more symptomatic intracranial hemorrhage (OR, 1.38; 95% CI, 1.21-1.56). However, in multivariable analysis, diabetes mellitus remained associated with less favorable outcome (OR, 0.77; 95% CI, 0.69-0.87) but not with symptomatic intracranial hemorrhage (OR, 1.11; 95% CI, 0.83-1.48). In unadjusted and in adjusted meta-analysis, higher AGL was associated with less favorable outcome and more symptomatic intracranial hemorrhage; the adjusted OR (95% CI) per 1 mmol/L increase in AGL was 0.92 (0.90-0.94) for favorable outcome, and 1.09 (1.04-1.14) for symptomatic intracranial hemorrhage.

Conclusions: These results confirm that AGL and history of diabetes mellitus are associated with poor clinical outcome after thrombolysis. AGL may be a surrogate marker of brain infarction severity rather than a causal factor. However, randomized controlled evidences are needed to address the significance of a tight glucose control during thrombolysis on clinical outcome.
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http://dx.doi.org/10.1161/STROKEAHA.111.000813DOI Listing
July 2013

Coronary artery disease and risk of major vascular events after cerebral infarction.

Stroke 2013 Jun 18;44(6):1505-11. Epub 2013 Apr 18.

INSERM U 698, Paris, France.

Background And Purpose: The impact of asymptomatic coronary artery disease on the risk of major vascular events in patients with cerebral infarction is unknown.

Methods: Four hundred five patients with acute cerebral infarction underwent carotid, femoral artery, thoracic, and abdominal aorta ultrasound examination. Of 342 patients with no known coronary heart disease, 315 underwent coronary angiography. We evaluated the 2-year risk of major vascular events (myocardial infarction, resuscitation after cardiac arrest, hospitalization for unstable angina or heart failure, stroke, or major peripheral arterial disease events) in patients with known coronary heart disease (n=63), and in the no known coronary heart disease group (n=315) as a function of coronary angiographic status (n=315).

Results: At 2 years, the estimated risk of major vascular events was 11.0% (95% confidence interval, 8.2-14.7). According to baseline coronary angiography, estimated risk was 3.4% in patients with no coronary artery disease (n=120), 8.0% with asymptomatic coronary artery stenosis <50% (n=113), 16.2% with asymptomatic coronary artery stenosis ≥ 50% (n=81), and 24.1% with known coronary heart disease (P<0.0001). Using no coronary artery disease as the reference, the age- and sex-adjusted hazard ratio (95% confidence interval) of vascular events was 2.10 (0.63-6.96) for asymptomatic coronary stenosis <50%, 4.36 (1.35-14.12) for asymptomatic coronary stenosis ≥ 50%, and 6.86 (2.15-21.31) for known coronary artery disease.

Conclusions: In patients with nonfatal cerebral infarction, presence and extent of asymptomatic stenoses on coronary angiography are strong predictors of major vascular events within 2 years.
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http://dx.doi.org/10.1161/STROKEAHA.111.000142DOI Listing
June 2013

Is intracerebral hemorrhage a time-dependent phenomenon after successful combined intravenous and intra-arterial therapy?

Stroke 2013 Mar 31;44(3):806-8. Epub 2013 Jan 31.

Department of Neurology, Bichat University Hospital, Paris, France.

Background And Purpose: Onset-to-reperfusion time (ORT) has recently emerged as an essential prognostic factor in acute ischemic stroke therapy. Although favorable outcome is associated with reduced ORT, it remains unclear whether intracranial bleeding depends on ORT. We therefore sought to determine whether ORT influenced the risk and volume of intracerebral hemorrhage (ICH) after combined intravenous and intra-arterial therapy.

Methods: Based on our prospective registry, we included 157 consecutive acute ischemic stroke patients successfully recanalized with combined intravenous and intra-arterial therapy between April 2007 and October 2011. Primary outcome was any ICH within 24 hours posttreatment. Secondary outcomes included occurrence of symptomatic ICH (sICH) and ICH volume measured with the ABC/2.

Results: Any ICH occurred in 26% of the study sample (n=33). sICH occurred in 5.5% (n=7). Median ICH volume was 0.8 mL. ORT was increased in patients with ICH (median=260 minutes; interquartile range=230-306) compared with patients without ICH (median=226 minutes; interquartile range=200-281; P=0.008). In the setting of sICH, ORT reached a median of 300 minutes (interquartile range=276-401; P=0.004). The difference remained significant after adjustment for potential confounding factors (adjusted P=0.045 for ICH; adjusted P=0.002 for sICH). There was no correlation between ICH volume and ORT (r=0.16; P=0.33).

Conclusions: ORT influences the rate but not the volume of ICH and appears to be a critical predictor of symptomatic hemorrhage after successful combined intravenous and intra-arterial therapy. To minimize the risk of bleeding, revascularization should be achieved within 4.5 hours of stroke onset.
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http://dx.doi.org/10.1161/STROKEAHA.112.675678DOI Listing
March 2013

Blood-brain barrier disruption is associated with increased mortality after endovascular therapy.

Neurology 2013 Feb 30;80(9):844-51. Epub 2013 Jan 30.

Department of Neurology and Stroke Centre, Bichat University Hospital.

Objective: To evaluate the incidence, baseline characteristics, and clinical prognosis of blood-brain barrier (BBB) disruption after endovascular therapy in acute ischemic stroke patients.

Methods: A total of 220 patients treated with endovascular therapy between April 2007 and October 2011 were identified from a prospective, clinical, thrombolysis registry. All patients underwent a nonenhanced CT scan immediately after treatment. CT scan or MRI was systematically realized at 24 hours to assess intracranial hemorrhage complications. BBB disruption was defined as a hyperdense lesion on the posttreatment CT scan.

Results: BBB disruption was found in 128 patients (58.2%; 95% confidence interval [CI], 51.4%-64.9%). Cardioembolic etiology, high admission NIH Stroke Scale score, high blood glucose level, internal carotid artery occlusion, and use of combined endovascular therapy (chemical and mechanical revascularization) were independently associated with BBB disruption. Patients with BBB disruption had lower rates of early major neurologic improvement (8.6% vs 31.5%, p < 0.001), favorable outcome (39.8% vs 61.8%, p = 0.002), and higher rates of 90-day mortality (34.4% vs 14.6%, p = 0.001) and hemorrhagic complications (42.2% vs 8.7%, p < 0.001) than those without BBB disruption. By multivariable analysis, patients with BBB disruption remained with a lower rate of early neurologic improvement (adjusted odds ratio [OR], 0.28; 95% CI, 0.11-0.70) and with a higher rate of mortality (adjusted OR, 2.37; 95% CI, 1.06-5.32) and hemorrhagic complications (adjusted OR, 6.38; 95% CI, 2.66-15.28).

Conclusion: BBB disruption has a detrimental effect on outcome and is independently associated with mortality after endovascular therapy. BBB disruption assessment may have a role in prognosis staging in these patients.
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http://dx.doi.org/10.1212/WNL.0b013e31828406deDOI Listing
February 2013

Outcomes after thrombolysis in AIS according to prior statin use: a registry and review.

Neurology 2012 Oct;79(17):1817-23

Department of Neurology and Stroke Centre, Bichat University Hospital, Paris, France.

Background: The impact of prior statin use on outcomes after thrombolysis is unclear. We evaluated outcomes of patients treated by IV, intra-arterial (IA) thrombolysis, or combined therapy, according to prior statin use.

Methods: We analyzed data from a patient registry (606 patients) and conducted a systematic review.

Results: We identified 11 previous studies (6,438 patients) that evaluated the effect of statin use on outcomes after IV thrombolysis (8 studies), IA thrombolysis (2 studies), or a single/combined approach (1 study). In our registry and in most of the retrieved studies, statin users had more risk factors and concomitant antiplatelet treatment than nonstatin users. Regardless of treatment strategy, prior statin use was not associated with favorable outcome (adjusted odds ratio [OR] 1.36; 95 confidence interval [CI] 0.86-2.16), symptomatic intracranial hemorrhage (sICH) (OR 0.57; 95% CI 0.22-1.49), or recanalization (OR 1.87; 95% CI 0.69-5.03). In meta-analysis, prior statin use was not associated with favorable outcome (crude OR 0.99; 95% CI 0.88-1.12), but was associated with an increased risk of sICH (crude OR 1.55; 95% CI 1.23-1.95). However, when the available multivariable associations were combined (5 studies), the effect of prior statin use on risk of sICH was not significant (OR 1.31; 95% CI 0.97-1.76).

Conclusions: These results suggest no beneficial or detrimental effect of prior statin use in acute stroke patients treated by IV thrombolysis, IA thrombolysis, or combined therapy, although the numbers of patients treated by IA thrombolysis or combined therapy are too small to exclude an effect.
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http://dx.doi.org/10.1212/WNL.0b013e318270400bDOI Listing
October 2012

Dramatic recovery in acute ischemic stroke is associated with arterial recanalization grade and speed.

Stroke 2012 Nov 30;43(11):2998-3002. Epub 2012 Aug 30.

Department of Neurology and Stroke Centre, Bichat University Hospital, INSERM U-698, Paris-Diderot University, 46, rue Henri Huchard, 75018 Paris, France.

Background And Purpose: Dramatic recovery (DR) is a predictor of stroke outcome among others. However, after successful recanalization, systematic favorable outcome is not the rule. We sought to analyze the impact of recanalization on DR in patients with acute ischemic stroke eligible for any revascularization strategies (either intravenous or endovascular).

Methods: We analyzed data collected between April 2007 and May 2011 in our prospective clinical registry. All patients with acute ischemic stroke with National Institutes of Health Stroke Scale≥10 at admission and an identification of arterial status before treatment were included. DR was defined as National Institutes of Health Stroke Scale≤3 at 24 hours or a decrease of ≥10 points within 24 hours.

Results: DR occurred in 75 of 255 patients with acute ischemic stroke (29.4%). Patients with persistent occlusion had a low DR rate (11.1%) than those with no documented occlusion (36.5%) and those with occlusion followed by recanalization (35.3%; both P<0.001). Among patients with recanalization monitored by angiography, DR was higher among patients with complete recanalization than among those with partial recanalization (46.8% versus 14.3%; P<0.001) and increased with tertiles of time to recanalization (Ptrend=0.002). In multivariable logistic regression analysis, grade and time to recanalization appeared independently associated with DR; the adjusted ORs were 4.17 (95% CI, 1.61-10.77) for complete recanalization and 1.24 (95% CI, 1.04-1.48) for each 30-minute time decrease. Patients with versus without DR more frequently had modified Rankin Scale≤1 (67.6% versus 9.0%; P<0.001) and less frequently had hemorrhage (17.3% versus 33.9%; P=0.024).

Conclusions: DR is strongly associated with favorable clinical outcome and is dependent on complete recanalization and time to recanalization.
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http://dx.doi.org/10.1161/STROKEAHA.112.658849DOI Listing
November 2012

Atherogenic dyslipidemia in patients with transient ischemic attack.

Stroke 2011 Aug 7;42(8):2131-7. Epub 2011 Jul 7.

INSERM U-698 and Paris-Diderot University, Department of Neurology and Stroke Centre, Bichat University Hospital, Paris, France.

Background And Purpose: There is mounting evidence that atherogenic dyslipidemia (ie, low high-density lipoprotein cholesterol combined with high triglyceride concentrations) is an independent predictor of high cardiovascular risk and possibly of stroke.

Methods: All patients included in the SOS-TIA cohort underwent an initial standardized evaluation, including medical history, physical examination, routine blood biochemistry, and diagnostic testing, and were followed for 1 year. Lipid profile was evaluated under fasting conditions. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol blood concentration ≤ 40 mg/dL and triglycerides ≥ 150 mg/dL.

Results: Among 1471 consecutive patients with transient ischemic attack (TIA) or minor stroke, overall prevalence of atherogenic dyslipidemia was 5.8%, but varied from 4.6% to 11.1%, depending on final diagnosis (possible TIA or TIA with a cerebral ischemic lesion, respectively). Prevalence of atherogenic dyslipidemia was independently associated with male sex, diabetes, and body mass index, but not with ABCD2 score. Atherogenic dyslipidemia also strongly associated with symptomatic intracranial stenosis ≥ 50% (adjusted odds ratio, 2.77; 95% CI, 1.38-5.55), but not with symptomatic extracranial stenosis ≥ 50% (adjusted odds ratio, 1.20; 95% CI, 0.64-2.26). Despite appropriate secondary prevention treatment, 90-day stroke risk was greater in patients with versus without atherogenic dyslipidemia (4.8% versus 1.7%; P=0.04).

Conclusions: The atherogenic dyslipidemia phenotype in patients with TIA may be associated with intracranial artery stenosis and higher risk of early recurrent stroke. Additional data are needed to confirm these findings and to assess the best way to reduce important residual risk in such patients.
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http://dx.doi.org/10.1161/STROKEAHA.110.609727DOI Listing
August 2011

Impact of a combined intravenous/intra-arterial approach in octogenarians.

Cerebrovasc Dis 2011 12;31(6):559-65. Epub 2011 Apr 12.

Department of Neurology and Stroke Centre, Bichat University Hospital, Paris, France.

Background: Intravenous (IV) alteplase is not currently recommended in octogenarian patients, and the benefit/risk ratio of endovascular (intra-arterial, IA) therapy remains to be determined. The aim of this study was to determine the impact of a combined IV-IA approach in octogenarians.

Methods: From a single-centre interventional study, we report age-specific outcomes of patients treated by a combined IV-IA thrombolytic approach. Patients ≥80 years with documented arterial occlusion treated by conventional IV thrombolysis constituted the control group.

Results: Among 84 patients treated by the IV-IA approach, those ≥80 years (n = 25) had a similar rate of early neurological improvement to that of patients <80 years, whereas the 90-day favourable outcome rate was lower in octogenarians (adjusted odds ratio, OR, 0.21; 95% confidence interval, CI, 0.06-0.75). No difference in symptomatic intracranial haemorrhage was observed whereas a higher rate of 90-day mortality (adjusted OR, 3.27; 95% CI, 0.76-14.14) and asymptomatic intracranial haemorrhage (adjusted OR, 6.39; 95% CI, 1.54-26.63) were found in patients ≥80 years old. Among octogenarians, and compared to IV-thrombolysis-treated patients (n = 24), patients treated by the IV-IA approach had a higher rate of recanalization (76 vs. 33%, p = 0.003) associated with increased early neurological improvement (32 vs. 8%, p = 0.07). Although there was a higher rate of asymptomatic intracranial haemorrhage (44 vs. 8%, p = 0.005) observed in the IV-IA group, no difference existed in symptomatic intracranial haemorrhage rates and 90-day favourable outcome.

Conclusion: The IV-IA approach in octogenarians was associated with lower efficacy at 3 months and higher mortality and asymptomatic haemorrhagic complications than in patients <80 years old. Definite recommendations cannot be given, but an endovascular approach may cause more harm than positive effects in patients over 80 years and should not be considered outside an approved protocol.
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http://dx.doi.org/10.1159/000324626DOI Listing
September 2011

Outcomes of mechanical endovascular therapy for acute ischemic stroke: a clinical registry study and systematic review.

Stroke 2011 May 24;42(5):1289-94. Epub 2011 Mar 24.

Department of Neurology and Stroke Centre, Bichat University Hospital, INSERM U-698 and Paris-Diderot University, 46, rue Henri Huchard, 75018 Paris, France.

Background And Purpose: Recanalization is a powerful predictor of stroke outcome in patients with arterial occlusion. Intravenous recombinant tissue plasminogen activator is limited by its recanalization rate, which may be improved with mechanical endovascular therapy (MET). However, the benefit and safety of MET remain to be determined. The aim of this study was to give reliable estimates of efficacy and safety outcomes of MET.

Methods: We analyzed data from our prospective clinical registry and conducted a systematic review of all previous studies using MET published between January 1966 and November 2009.

Results: From April 2007 to November 2009, 47 patients with acute stroke were treated with MET at Bichat Hospital. The literature search identified 31 previous studies involving a total of 1066 subjects. In the meta-analysis, including our registry data, the overall recanalization rate was 79% (95% CI, 73-84). Meta-analysis of clinical outcomes showed a pooled estimate of 40% (95% CI, 34-46; 27 studies) for favorable outcome, 28% (95% CI, 23-33; 28 studies) for mortality, and 8% (95% CI, 6-10; 27 studies) for symptomatic intracranial hemorrhage. The likelihood of a favorable outcome increased with the use of thrombolysis (OR, 1.99; 95% CI, 1.23-3.22) and with proportion of patients with isolated middle cerebral artery occlusion (OR per 10% increase, 1.14; 95% CI, 1.04-1.25).

Conclusions: MET is associated with acceptable safety and efficacy in stroke patients, and it may be a therapeutic option in those presenting with isolated middle cerebral artery occlusion.
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http://dx.doi.org/10.1161/STROKEAHA.110.599399DOI Listing
May 2011

Prevalence of coronary atherosclerosis in patients with cerebral infarction.

Stroke 2011 Jan 18;42(1):22-9. Epub 2010 Nov 18.

INSERM U-698 and Paris-Diderot University, Paris, France.

Background And Purpose: there is an overlap between stroke and coronary heart disease, but the exact prevalence of coronary artery disease in patients with nonfatal cerebral infarction is unclear, particularly when there is no known history of coronary heart disease.

Methods: we consecutively enrolled 405 patients presenting with acute cerebral infarction documented by neuroimaging who underwent carotid and femoral artery, thoracic, and abdominal aorta ultrasound examinations. Of the 342 patients with no known coronary heart disease, 315 underwent coronary angiography a median of 8 days (interquartile range, 6-11) after stroke onset.

Results: coronary plaques on angiography, regardless of stenosis severity, were present in 61.9% of patients (95% confidence interval [CI], 56.5-67.3) and coronary stenoses ≥ 50% were found in 25.7% (95% CI, 20.9-30.5). The overall prevalence of coronary plaque increased with the number of arterial territories (carotid or femoral arteries) involved, with an adjusted odds ratio of coronary artery disease of 1.25 (95% CI, 0.58-2.71) for presence of plaque in 1 territory, and 4.31 (95% CI, 1.92-9.68) for presence of plaque in both territories, compared with no plaque in either territory. The presence of plaque in both femoral and carotid arteries had an age- and sex-adjusted positive predictive value of 84% for presence of coronary plaque and a negative predictive value of 44%.

Conclusions: there is a high burden of silent coronary artery disease in patients with nonfatal cerebral infarction and no known coronary heart disease, even in the absence of systemic atherosclerosis. The prevalence is even higher in patients with evidence of carotid and/or femoral plaque.
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http://dx.doi.org/10.1161/STROKEAHA.110.584086DOI Listing
January 2011

Yield of systematic transcranial Doppler in patients with transient ischemic attack.

Ann Neurol 2010 Jul;68(1):9-17

INSERM-U698 and Denis Diderot University and Medical School, Paris, France.

Objective: Urgent evaluation and treatment of transient ischemic attack (TIA) patients in a dedicated TIA clinic may reduce the 90-day stroke risk by 80%. ABCD2 (Age, Blood pressure, Clinical features, Duration, Diabetes) score and magnetic resonance imaging abnormalities help to identify patients at high risk of stroke. Our aim was to determine whether the use of transcranial Doppler (TCD) examination on arrival at the TIA clinic yields additional information that facilitates the identification of patients at high risk of stroke recurrence.

Methods: Between January 2003 and December 2007, 1,881 patients were admitted to SOS-TIA clinic (a TIA clinic with around-the-clock access). Clinical and vascular assessment included TCD performed by a neurologist immediately after admission. Stroke prevention measures were initiated on arrival, in accordance with guidelines. All patients were followed for 1 year after presentation to the SOS-TIA clinic.

Results: A total of 1,823 TCD examinations were performed within 4 hours of admission. Intracranial narrowing or occlusion was found in 8.8% of patients, and was independently associated with age, hypertension, and diabetes. After 1-year follow-up on best preventive therapy, the incidence of recurrent vascular events (intracranial revascularization for TIA recurrence, stroke, myocardial infarction, and vascular death combined) was 7.0% in patients with intracranial narrowing or occlusion and 2.4% in those without (log-rank, p = 0.007). The hazard ratio of combined outcome for the presence of intracranial narrowing or occlusion was 2.29 (95% confidence interval [CI], 1.15-4.56; p = 0.02) in multivariate analysis including age, gender, hypertension, and diabetes, and was 2.50 (95%CI, 1.24-5.05; p = 0.01) in multivariate analysis including ABCD2 score > or =4.

Interpretation: Immediate TCD examination on arrival at the TIA clinic is feasible and could help to identify patients at high risk of vascular events recurrence. This study supports a systematic intracranial vascular examination in the initial management of TIA.
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http://dx.doi.org/10.1002/ana.21921DOI Listing
July 2010

Hypertrophic remodeling and increased arterial stiffness in patients with intracranial aneurysms.

Atherosclerosis 2010 Aug 13;211(2):486-91. Epub 2010 Apr 13.

Department of Neurology, CHU-Hopitaux de Rouen & Institut National de la Sante et de la Recherche Medicale (INSERM) U644, Institut Federatif de Recherche Multidisciplinaire sur les Peptides (IFRMP) 23, Institute for Biomedical Research, University of Rouen, France.

Objective: Because an underlying arteriopathy might contribute to the development of intracranial aneurysms (IAs), we assessed the elastic properties of proximal conduit arteries in patients with IA.

Methods: In 27 patients with previous ruptured IA and 27 control subjects matched for age, gender and BMI, we determined arterial pressure, internal diameter, intima-media thickness (IMT), circumferential wall stress (CWS) and elastic modulus (wall stiffness) in common carotid arteries using applanation tonometry and echotracking. Moreover, carotid augmentation index (AIx, arterial wave reflections) and carotid-to-femoral pulse wave velocity (PWV, aortic stiffness) were assessed.

Results: Compared with controls, patients with IA exhibited higher brachial and carotid systolic and diastolic blood pressures, with similar brachial but higher carotid artery pulse pressure (35 + or - 6mm Hg vs. 41 + or - 8mm Hg, P=0.014). Moreover, patients have higher PWV (7.8 + or - 1.2ms(-1) vs. 8.3 + or - 1.1ms(-1), P=0.048) and AIx (15.8 + or - 10.8% vs. 21.1 + or - 8.5%, P<0.001) which contributes to increase carotid blood pressures. Furthermore, carotid IMT was higher in patients (546 + or - 64 microm vs. 642 + or - 70 microm, P<0.001) without difference in diameter suggesting an adaptive hypertrophy. However, patients display a lower CWS (61.6 + or - 9.2 kPa vs. 56.9 + or - 10.3 kPa, P=0.007) and no correlation between IMT and pulse pressure (r=0.152, P=NS) in contrast to controls (r=0.539, P<0.001) showing the contribution of a pressure-independent process. Finally, despite this lesser CWS, elastic modulus was increased in patients (310 + or - 105 kPa vs. 383 + or - 174 kPa, P=0.026).

Conclusion: This study demonstrates that patients with IA display a particular carotid artery phenotype with an exaggerated hypertrophic remodeling and altered elastic properties. Thus, a systemic arteriopathy might contribute, together with the arterial wall fatiguing effect of the increased pulsatile stress, to the pathogenesis of IA.
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http://dx.doi.org/10.1016/j.atherosclerosis.2010.04.002DOI Listing
August 2010

Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study.

Lancet Neurol 2009 Sep 31;8(9):802-9. Epub 2009 Jul 31.

Department of Neurology and Stroke Centre, Bichat University Hospital, Paris, France; Diderot University, Paris, France.

Background: The efficacy of intravenous (IV) alteplase is restricted by the speed of recanalisation and the site of the occlusion. The aim of this study was to ascertain the effect of a combined IV-endovascular approach (intra-arterial alteplase and, if required, additional thrombectomy) in patients with stroke due to arterial occlusion.

Methods: We compared recanalisation rates, neurological improvement at 24 h, and functional outcome at 3 months between two periods (February, 2002, to March, 2007, vs April, 2007, to October, 2008) in patients in a prospective registry who were treated with different regimens of alteplase within 3 h of symptom onset. Patients with confirmed occlusion who were treated before April, 2007, were treated with IV alteplase; after April, 2007, patients were treated with a systematic IV-endovascular approach. Analysis was by intention to treat.

Findings: 46 (87%) of 53 patients treated with the IV-endovascular approach achieved recanalisation versus 56 (52%) of 107 patients in the IV group (adjusted relative risk [RR] 1.49, 95% CI 1.21-1.84; p=0.0002). Early neurological improvement (NIHSS score of 0 or 1 or an improvement of 4 points or more at 24 h) occurred in 32 (60%) patients in the IV-endovascular group and 42 (39%) patients in the IV group (adjusted RR 1.36, 0.97-1.91; p=0.07). Favourable outcome (mRS of 0-2 at 90 days) occurred in 30 (57%) patients in the IV-endovascular group and 47 (44%) patients in the IV group (adjusted RR 1.16, 0.85-1.58; p=0.35). The mortality rate at 90 days was 17% in both groups, and symptomatic intracranial haemorrhage was reported in five (9%) patients in the IV-endovascular group and in 12 (11%) patients in the IV group. Better clinical outcome was associated with recanalisation in both groups and with time to recanalisation in the IV-endovascular group.

Interpretation: An IV-endovascular approach is associated with higher recanalisation rates than is IV alteplase in patients with stroke and confirmed arterial occlusion. In patients treated with an IV-endovascular approach, a shorter time from symptom onset to recanalisation is associated with better clinical outcomes.
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http://dx.doi.org/10.1016/S1474-4422(09)70182-6DOI Listing
September 2009

Does ABCD2 score below 4 allow more time to evaluate patients with a transient ischemic attack?

Stroke 2009 Sep 11;40(9):3091-5. Epub 2009 Jun 11.

Department of Neurology and Stroke Center, Paris, France.

Background And Purpose: The National Institute for Clinical Excellence (NICE) recommends that patients with a transient ischemic attack and ABCD(2) score > or =4 and those with >2 transient ischemic attacks within 1 week be admitted for urgent complete etiologic evaluation within 24 hours and that those with an ABCD(2) score <4 be evaluated less urgently within 1 week.

Methods: Using data from 1176 patients with a definite or possible transient ischemic attack or minor stroke included in the SOS-TIA registry (January 2003 to June 2007), we studied the usefulness of the conventional ABCD(2) score cutoff as well as the NICE criteria for urgent admission to a stroke unit defined as presence of symptomatic internal carotid artery stenosis > or =50%, symptomatic intracranial artery stenosis > or =50%, or major cardiac source of embolism.

Results: Among 697 patients with an ABCD(2) score <4, 20% required immediate consideration for emergency treatment (eg, symptomatic internal carotid stenosis > or =50% in 9.1% of patients, symptomatic intracranial stenosis in 5.0%, atrial fibrillation in 5.9%, other major cardiac source of embolism in 2.1%) in comparison to 31.6% of 497 patients with an ABCD(2) score > or =4. The sensitivity and specificity of ABCD(2) score > or =4 or NICE criteria for discriminating between patients requiring admission or not were <62% with low positive predictive values (<30%) and high negative predictive values (> or =80%).

Conclusions: One in 5 patients with an ABCD(2) score <4 had high-risk disease requiring urgent treatment decision-making. When triaging on an ABCD(2) score, we recommend adding systematic carotid ultrasound (or a default angiographic CT scan) and electrocardiography within 24 hours before postponing complete transient ischemic attack evaluation.
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http://dx.doi.org/10.1161/STROKEAHA.109.552042DOI Listing
September 2009

Outcomes of intravenous recombinant tissue plasminogen activator therapy according to gender: a clinical registry study and systematic review.

Stroke 2009 Jun 16;40(6):2104-10. Epub 2009 Apr 16.

INSERM U-698 and Paris-Diderot University, Paris, France.

Background And Purpose: The natural history of stroke is worse in women than in men. Controversial data have been published on the efficacy of thrombolysis with recombinant tissue plasminogen activator (rtPA) according to gender. We evaluated gender differences in the efficacy and safety outcomes of intravenous rtPA using a clinical registry and systematic review.

Methods: Since January 2002, we collected baseline characteristics and efficacy and safety outcomes for patients who received intravenous rtPA in our center. We performed a systematic PubMed literature search for previous observational studies that examined gender effects on outcomes after intravenous rtPA treatment.

Results: No gender difference in good outcome at 3 months (adjusted OR for women, 1.41; 95% CI, 0.76 to 2.60) and in 90-day mortality (adjusted OR, 1.38; 95% CI, 0.59 to 3.19) was found in our registry. We identified 16 studies that evaluated the gender effect among intravenous rtPA-treated patients. None of these studies supported a gender difference in favorable outcome, and one suggested an increased risk of mortality in men. In unadjusted partial meta-analysis in 4074 women and 5840 men including our registry data, we found a trend toward a lower risk of symptomatic intracranial hemorrhage in women (crude OR, 0.87; 95% CI, 0.68 to 1.10).

Conclusions: These results suggest no gender difference in outcome among patients treated with intravenous rtPA.
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http://dx.doi.org/10.1161/STROKEAHA.108.546325DOI Listing
June 2009

A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects.

Lancet Neurol 2007 Nov;6(11):953-60

Department of Neurology and Stroke Centre, Bichat-Claude Bernard University Hospital, Denis Diderot University and Medical School-Paris VII, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: Diagnosis and treatment of cerebral and retinal transient ischaemic attacks (TIAs) are often delayed by the lack of immediate access to a dedicated TIA clinic. We evaluated the effects of rapid assessment of patients with TIA on clinical decision making, length of hospital stay, and subsequent stroke rates.

Methods: We set up SOS-TIA, a hospital clinic with 24-h access. Patients were admitted if they had sudden retinal or cerebral focal symptoms judged to relate to ischaemia and if they made a total recovery. Assessment, which included neurological, arterial, and cardiac imaging, was within 4 h of admission. A leaflet about TIA with a toll-free telephone number for SOS-TIA was sent to 15 000 family doctors, cardiologists, neurologists, and ophthalmologists in Paris and its administrative region. Endpoints were stroke within 90 days, and stroke, myocardial infarction, and vascular death within 1 year.

Findings: Between January, 2003, and December, 2005, we admitted 1085 patients with suspected TIA; 574 (53%) were seen within 24 h of symptom onset. 701 (65%) patients had confirmed TIA or minor stroke, and 144 (13%) had possible TIA. 108 (17%) of the 643 patients with confirmed TIA had brain tissue damage. Median duration of symptoms was 15 min (IQR 5-75 min). Of the patients with confirmed or possible TIA, all started a stroke prevention programme, 43 (5%) had urgent carotid revascularisation, and 44 (5%) were treated for atrial fibrillation with anticoagulants. 808 (74%) of all patients seen were sent home on the same day. The 90-day stroke rate was 1.24% (95% CI 0.72-2.12), whereas the rate predicted from ABCD(2) scores was 5.96%.

Interpretation: Use of TIA clinics with 24-h access and immediate initiation of preventive treatment might greatly reduce length of hospital stay and risk of stroke compared with expected risk.
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http://dx.doi.org/10.1016/S1474-4422(07)70248-XDOI Listing
November 2007

Phenotype associated with APP duplication in five families.

Brain 2006 Nov 7;129(Pt 11):2966-76. Epub 2006 Sep 7.

Department of Neurology, University Hospital IFRMP, France.

Different duplications of the APP locus have been identified in five families with autosomal dominant early onset Alzheimer's disease (ADEOAD) and Abeta-related cerebral amyloid angiopathy (CAA). This study describes the phenotype of this new entity. Clinical, neuropsychological, imagery and neuropathological data were reviewed. The phenotype was not dependent on the size of the duplication and there was no clinical feature of Down's syndrome. Dementia was observed in all cases; intracerebral haemorrhage (ICH) was reported in 6 (26%) and seizures occurred in 12 (57%) of 21 patients. Age of onset of dementia ranged from 42 to 59 years, ICH from 53 to 64 years and age at death from 46 to 75 years. The neuropathological findings in five cases demonstrated Alzheimer's disease and severe CAA lesions that were reminiscent from those reported in brains of Down's syndrome patients. A striking feature consisted in intraneuronal Abetax-40 accumulation located in the granular cell layer of the dentate gyrus and in the pyramidal cell layer of the Ammon's horn.
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http://dx.doi.org/10.1093/brain/awl237DOI Listing
November 2006