Publications by authors named "Emmanuel Touzé"

147 Publications

Patent Foramen Ovale Closure In Stroke Patients With Migraine In The Close Trial. The Close-Mig Study.

Eur J Neurol 2021 May 3. Epub 2021 May 3.

Stroke unit, Department of Neurology, University Hospital of Nantes, Nantes, France.

Background: The efficacy of patent foramen ovale (PFO) closure to reduce the frequency of migraine attacks remains controversial.

Methods: Planned sub-study in migraine patients enrolled in a randomized, clinical trial designed to assess the superiority of PFO closure plus antiplatelet therapy over antiplatelet therapy alone to prevent stroke recurrence in patients younger than 60 years with a PFO-associated cryptogenic ischemic stroke. The main outcome was the mean annual number of migraine attacks in migraine patients with aura and in those without aura, as recorded at each follow-up visit by study neurologists.

Results: Among 473 patients randomized to PFO closure or antiplatelet therapy, 145 (mean age, 41.9 years; women 58.6%) had migraine (75 with aura and 70 without aura). Sixty-seven patients were randomized to PFO closure and 78 to antiplatelet therapy. During a mean follow-up of about 5 years, there were no differences between antiplatelet-only and PFO closure groups in the mean annual number of migraine attacks, both in migraine patients with aura (9.2 [11.9] vs 12.0 [19.1], p = 0.81) and in those without aura (12.1 [16.1] vs 11.8 [18.4], p > 0.999). There were no differences between treatment groups regarding cessation of migraine attacks, migraine-related disability at 2 years and use of migraine-preventive drugs during follow-up.

Conclusions: In young and middle-aged adults with PFO-associated cryptogenic stroke and migraine, PFO closure plus antiplatelet therapy did not reduce the mean annual number of migraine attacks compared to antiplatelet therapy alone, both in migraine patients with and without aura.
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http://dx.doi.org/10.1111/ene.14892DOI Listing
May 2021

Susceptibility Vessel Sign in Relation With Time From Onset to Magnetic Resonance Imaging.

Stroke 2021 May 8;52(5):1839-1842. Epub 2021 Apr 8.

Université Caen-Normandie, INSERM UMR-S U1237, Cyceron, Caen, France (S.S., M.G., M.Z., E.T.).

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.032198DOI Listing
May 2021

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.

Cardiovasc Res 2021 Mar 19. Epub 2021 Mar 19.

Department of Hypertension, National Institute of Cardiology, Warsaw, Poland.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string of beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research which has led to improved understandings of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.
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http://dx.doi.org/10.1093/cvr/cvab086DOI 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

Decongestant use and the risk of myocardial infarction and stroke: a case-crossover study.

Sci Rep 2021 Feb 18;11(1):4160. Epub 2021 Feb 18.

Normandie Université, Université Caen Normandie, CHU Caen Normandie, Inserm U1237, Caen, France.

Pharmacovigilance reports of cerebral and cardiovascular events in those who use decongestants have triggered alerts related to their use. We aimed to assess the risk of stroke and myocardial infarction (MI) associated with the use of decongestants. We conducted a nested case-crossover study of patients with incident stroke and MI identified in France between 2013 and 2016 in two systematic disease registries. Decongestant use in the three weeks preceding the event was assessed using a structured telephone interview. Conditional logistic multivariable models were used to estimate the odds of incident MI and stroke, also accounting for transient risk factors and comparing week 1 (index at-risk time window, immediately preceding the event) to week 3 (reference). Time-invariant risk factors were controlled by design. In total, 1394 patients with MI and 1403 patients with stroke, mainly 70 years old or younger, were interviewed, including 3.2% who used decongestants during the three weeks prior to the event (1.0% definite exposure in the index at-risk time window, 1.1% in the referent time window; adjusted odds ratio (aOR), 0.78; 95%CI, 0.43-1.42). Secondary analysis yielded similar results for individual events (MI/stroke). We observed no increased risk of MI or stroke for patients 70 years of age and younger without previous MI or stroke who used decongestants.
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http://dx.doi.org/10.1038/s41598-021-83718-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893034PMC
February 2021

Cervical arterial abnormalities and outcome after aneurysmal subarachnoid haemorrhage: A pilot cohort study.

Anaesth Crit Care Pain Med 2020 12 7;39(6):832-836. Epub 2020 Aug 7.

Normandie Univ, UNICAEN, INSERM U1237, Physiopathology and imaging of neurological disorders (PhIND), GIP Cyceron, 14000, France; Normandie Univ, UNICAEN, CHU de Caen, Service de Radiologie, 14000 Caen, France.

Background: Cervical arterial abnormalities are associated with intracranial aneurysm but their frequency and association with outcome in case of aneurysmal subarachnoid haemorrhage (aSAH) remains unknown.

Methods: Data were retrospectively extracted from a prospective database. Consecutive angiographies of aSAH patients on a 13-month period were reviewed as well as consecutive angiographies of SAH patients without evidence of aneurysm on a 20-month period. Occurrence of secondary neurological complications was collected with 3-month functional outcome (modified Rankin Scale ≥ 3 was considered as poor outcome). Cervical arterial abnormalities on angiographies were classified into two subcategories: trajectory and lumen vessel abnormalities.

Results: Forty-five patients displayed aneurysmal rupture (aSAH) while 39 patients had no evidence of aneurysm (non-aneurysmal SAH). Prevalence of cervical arterial abnormalities in aSAH and non-aneurysmal SAH patients were 82% (n = 37) and 64% (n = 25), respectively (p =  0.082). Lumen vessel abnormalities were significantly more frequent in case of aSAH (n = 31; 69%) than non-aneurysmal SAH: (n = 9; 23%; p < 0.001). Twenty-eight (62%) aSAH patients experienced poor outcome at 3 months. Lumen vessel abnormalities were significantly associated with 3-month poor outcome (74% (n = 23) versus 36% (n = 5); p =  0.021) without any significant increased occurrence of secondary complications such arterial vasospasm or delayed cerebral ischemia.

Conclusion: Cervical arterial abnormalities are frequent in a cohort of aSAH patients. Lumen vessel abnormalities are associated with 3-month poor outcome.
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http://dx.doi.org/10.1016/j.accpm.2020.03.020DOI Listing
December 2020

Interventional neuroradiology in France, quo vadis?

J Neuroradiol 2021 Feb 10;48(1):2-4. Epub 2020 Jul 10.

Radiology department, centre hospitalier Lyon-Sud, hospices civils de Lyon, 69310 Pierre-Bénite, France; Inserm U1044, CNRS UMR 5220, CREATIS, université Lyon-1, 69100 Villeurbanne, France. Electronic address:

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http://dx.doi.org/10.1016/j.neurad.2020.07.001DOI Listing
February 2021

Impact of Sex on Office White Coat Effect Tail: Investigating Two Italian Residential Cohorts.

Sci Rep 2019 11 21;9(1):17237. Epub 2019 Nov 21.

Normandie Université, UNICAEN, EA 4650, Signalisation, électrophysiologie et imagerie des lésions d'ischémie reperfusion myocardique, 14000, Caen, France.

To assess the impact of sex on office white-coat effect tail (OWCET), the waning of systolic blood pressure (SBP) after its waxing during office visit, on the incidence of long-term major fatal and non-fatal events in two Italian residential cohorts [from the Gubbio Study and the Italian Rural Areas of the Seven Countries Study (IRA)]. There were 3565 persons (92 with missing data, 44% men, 54 ± 11 years) included in the Gubbio and 1712 men (49 ± 5 years) in the IRA studies. OWCET was defined as a decrease of ≥10 mmHg in SBP between successive measurements with slight measurement differences between the two cohorts. Cardiovascular (CVD), coronary heart disease (CHD) and stroke (STR) incidences were considered. Over an approximately 20-year follow-up, women with OWCET had an increased risk of CVD [HR: 1.591 (95%CI: 1.204-2.103)], CHD [HR: 1.614 (95%CI: 1.037-2.512)] and STR [HR: 1.696 (95%CI: 1.123-2.563)] events independently of age, serum and HDL cholesterol, cigarettes, BMI and SBP in the Gubbio study. However, there was no increased risk of CVD, CHD or STR in men with OWCET neither in the Gubbio 20-year follow-up nor in the IRA 50-year follow-up. These results were not modified significantly by the correction of the regression dilutions bias between the first and the subsequent SBP measurements. Thus, in primary care, OWCET should be actively evaluated in women as it can improve stratification of long-term CVD, CHD and STR risks.
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http://dx.doi.org/10.1038/s41598-019-53109-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872870PMC
November 2019

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

Essen Risk Score in Prediction of Myocardial Infarction After Transient Ischemic Attack or Ischemic Stroke Without Prior Coronary Artery Disease.

Stroke 2019 12 22;50(12):3393-3399. Epub 2019 Oct 22.

From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, United Kingdom (M.B., L.L., S.L., N.G.L., M.M.K., L.S., P.M.R.).

Background and Purpose- More intensive secondary prevention with newer drugs may be cost-effective in patients with coronary artery disease (CAD). Whether some subgroups of patients who had a transient ischemic attack (TIA) or ischemic stroke, but no prior CAD are at similar high risk of myocardial infarction as those with prior CAD remains unclear. We determined whether the Essen score identified a subset of TIA/stroke patients without known prior CAD who, nevertheless, had a high risk of myocardial infarction on current secondary prevention management. Methods- In a population-based cohort (Oxford Vascular Study) of consecutive TIA or ischemic stroke patients recruited from 2002 to 2014, 10-year actuarial risks of myocardial infarction and of recurrent ischemic stroke were determined by face-to-face follow-up in patients with and without prior CAD using Kaplan-Meier analyses. Predictive value of the Essen score was assessed with C statistic. Results- Of 2555 patients with TIA/stroke (13 070 patient-years of follow-up), 10-year risk of myocardial infarction in those without prior CAD (n=2017, 78.9%) ranged from 0.9% (95% CI, 0-1.9) at Essen score ≤1 to 29.8% (95% CI, 7.7-46.6) in those with a score ≥5 (C statistic =0.64 [95% CI, 0.57-0.71]; <0.001). The score tended to be less predictive (difference: =0.0460) for the risk of recurrent ischemic stroke (C statistic =0.57 [95% CI, 0.54-0.60]). Compared with patients with prior CAD (n=538, 21.1%), an Essen risk score of ≥4 (n=294, 11.5%) in those without prior CAD identified a subgroup at similar high 10-year risks of myocardial infarction (17.2% [95% CI, 6.9-26.3] versus 16.9% [95% CI, 11.5-22.0]) and of recurrent stroke (40.4% [95% CI, 26.7-51.6] versus 32.4% [95% CI, 25.2-38.8]). Conclusions- The Essen score is a simple clinical score to risk-stratify patients with TIA/stroke without prior CAD and to identify subsets who may be at sufficiently high risk of myocardial infarction and recurrent stroke to justify more intensive treatment or inclusion in trials.
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http://dx.doi.org/10.1161/STROKEAHA.119.025831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597993PMC
December 2019

White-coat hypertension: management and adherence to guidelines by European and Canadian GPs. A cross-sectional clinical vignette study.

BJGP Open 2019 Oct 1. Epub 2019 Oct 1.

Physician and Professor, Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.

Background: White-coat hypertension (WCH) is also referred to as 'isolated clinic hypertension'. While it is a frequently encountered phenomenon, WCH is not systematically evoked, and its management remains unclear due to the contradictory guidelines provided by professional societies.

Aim: To examine WCH management by GPs in Europe and Canada.

Design & Setting: A clinical vignette of a possible case of WCH was created from the literature, and the responses of GPs to WCH-specific questions in a cross-sectional electronic questionnaire were compared.

Method: Complete electronic questionnaire responses from Europe and Canada were systematically analysed.

Results: Among 770 eligible questionnaires (useful response rate: 10.6%), 43.5% were from France, 19.2% from Belgium, 7.8% from England, 19.5% from Switzerland, and 10.0% from Canada. Based on the clinical information provided in the vignette, GPs overall diagnosed hypertension and WCH equally (50.7% versus 49.3%, respectively). Canadian GPs suggested hypertension more frequently than European GPs in general (64.2% versus 46.1%, <10), and more frequently used ambulatory blood pressure monitoring ([ABPM] 42.3% versus 26.1%, = 0.01). In both groups of GPs, WCH was managed similarly (no treatment, 100% versus 97.3%, = 0.39). Generally, the GPs all followed WCH patients for 3-6 months (51.3% versus 66.2%, = 0.1), and they were not aware of the WCH guidelines (47.3% versus 52.1%, = 0.54).

Conclusion: Although WCH guidelines are different, WCH management by GPs is very similar except for diagnosis. Homogeneity in WCH guidelines is required and should be systematically implemented in hypertension guidelines to avoid inappropriate management of the condition.
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http://dx.doi.org/10.3399/bjgpopen19X101664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995860PMC
October 2019

Effect of coexisting vascular disease on long-term risk of recurrent events after TIA or stroke.

Neurology 2019 08 23;93(7):e695-e707. Epub 2019 Jul 23.

From the Centre for Prevention of Stroke and Dementia (M.B., L.L., S.L., N.G.L., M.M.K., L.S., P.M.R.), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, UK; and Service de Neurologie (M.B., E.T.), CHU Caen Normandie, UNICAEN, Normandie Université, INSERM U1237, Caen, France.

Objective: To determine whether patients with TIA or ischemic stroke with coexisting cardiovascular disease (i.e., history of coronary or peripheral artery disease) are still at high risk of recurrent ischemic events despite current secondary prevention guidelines.

Methods: In a population-based study in Oxfordshire, UK (Oxford Vascular Study), we studied consecutive patients with TIA or ischemic stroke for 2002-2014. Patients were treated according to current secondary prevention guidelines and we determined risks of coronary events, recurrent ischemic stroke, and major bleeding stratified by the presence of coexisting cardiovascular disease.

Results: Among 2,555 patients (9,148 patient-years of follow-up), those (n = 640; 25.0%) with coexisting cardiovascular disease (449 coronary only; 103 peripheral only; 88 both) were at higher 10-year risk of coronary events than those without (22.8%, 95% confidence interval 17.4-27.9; vs 7.1%, 5.3-8.8; < 0.001; age- and sex-adjusted hazard ratio [HR] 3.07, 2.24-4.21) and of recurrent ischemic stroke (31.5%, 25.1-37.4; vs 23.4%, 20.5-26.2; = 0.0049; age- and sex-adjusted HR 1.23, 0.99-1.53), despite similar rates of use of antithrombotic and lipid-lowering medication. However, in patients with noncardioembolic TIA/stroke, risk of extracranial bleeds was also higher in those with coexisting cardiovascular disease, particularly in patients aged <75 years (8.1%, 2.8-13.0; vs 3.4%, 1.6-5.3; = 0.0050; age- and sex-adjusted HR 2.71, 1.16-6.30), although risk of intracerebral hemorrhage was not increased (age- and sex-adjusted HR 0.36, 0.04-2.99).

Conclusions: As in older studies, patients with TIA/stroke with coexisting cardiovascular disease remain at high risk of recurrent ischemic events despite current management. More intensive lipid-lowering might therefore be justified, but benefit from increased antithrombotic treatment might be offset by the higher risk of extracranial bleeding.
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http://dx.doi.org/10.1212/WNL.0000000000007935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715511PMC
August 2019

Apixaban for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in France: The PAROS cross-sectional study of routine clinical practice.

Arch Cardiovasc Dis 2019 Jun - Jul;112(6-7):400-409. Epub 2019 Apr 20.

Department of Cardiology, Hôpital Bichat, AP-HP, 75018 Paris, France; Inserm U1148, Université Paris Diderot, 75877 Paris, France. Electronic address:

Background: Non-vitamin K antagonist oral anticoagulants (NOACs), including apixaban, are recommended for prevention of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF).

Aims: To describe the characteristics of patients starting anticoagulant treatment, identify the characteristics associated with apixaban prescription, and describe apixaban use in France.

Methods: This was a non-interventional multicentre French study. Patients with NVAF (aged≥18 years) with anticoagulant treatment started in the preceding 3 months were evaluated in four groups (NOAC [apixaban, dabigatran or rivaroxaban] or vitamin K antagonist [VKA]).

Results: Data from 2027 patients were eligible for analysis. Mean age was 73.0±11.2 years, 56.6% were men and 80.2% were anticoagulant naïve. Stage≥4 chronic kidney disease was present in 2.2% of patients prescribed apixaban, none of those prescribed dabigatran or rivaroxaban, and 16.8% of those prescribed VKAs. The median CHADS-VASc score was 3 for all three NOACs and 4 for VKAs; the median HAS-BLED score was≥3 for 2.5-5.9% of patients prescribed NOACs and 12.0% of those prescribed VKAs. Apixaban was more likely to be prescribed than other NOACs in older patients with higher bleeding risk and decreased renal function, and VKAs in patients with lower bleeding risk and better renal function. Patients received a reduced dose (5mg/day; 30.4% patients) or a full dose (10mg/day; 69.6% patients) of apixaban. Only 79.3% of patients prescribed apixaban had doses consistent with the summary of product characteristics; underdosing was more frequent than overdosing. Off-label use of apixaban was observed, mainly in elderly patients, despite normal renal function and weight.

Conclusions: Initiation of apixaban versus NOACs was more common among patients with increased age, higher bleeding risk and decreased renal function, whereas initiation of apixaban versus VKAs was more common among patients with lower bleeding risk and better renal function.
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http://dx.doi.org/10.1016/j.acvd.2019.02.003DOI Listing
December 2019

First-line contact aspiration vs stent-retriever thrombectomy in acute ischemic stroke patients with large-artery occlusion in the anterior circulation: Systematic review and meta-analysis.

Interv Neuroradiol 2019 Jun 4;25(3):244-253. Epub 2019 Feb 4.

4 Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Nancy, Nancy, France.

Background: In acute ischemic stroke patients with large-artery occlusion, uncertainties remain about whether clinically important outcomes are comparable between first-line contact aspiration and stent-retriever thrombectomy, although two trials have investigated whether one strategy should be preferred over another.

Purpose: The purpose of this article is to compare the efficacy and safety of first-line contact aspiration and stent-retriever thrombectomy in stroke patients with anterior circulation large-artery occlusion.

Methods: We undertook a systematic review of studies of patients treated for large-artery occlusion, with the latest devices of either strategy, within six hours of stroke onset. We determined rates of final complete reperfusion (defined as modified Thrombolysis In Cerebral Infarction score = 3), periprocedural complications and 90-day functional independence (defined as modified Rankin Scale (mRS) score 0-2), and excellent outcome (defined as mRS score 0-1) after contact aspiration and after stent-retriever thrombectomy using random-effects meta-analyses. Any differential effects in rates between the two strategies were assessed using random-effects meta-regressions.

Results: Fifteen studies (1817 patients) were included. There was no difference in rates of final complete reperfusion at the end of all endovascular procedures between contact aspiration and stent retrievers (51.1%, 95% confidence interval (CI) 39.3-62.9; vs 38.3%, 95% CI 28.6-48.0; p = 0.14), 90-day functional independence (45.0%, 40.7-49.2; vs 52.4%, 47.7-57.1; p = 0.45) and excellent outcome (32.1%, 25.7-38.5; vs 34.1%, 21.2-46.9; p = 0.94). Rates of periprocedural complications did not differ between the two strategies.

Conclusions: Current data suggest no difference in efficacy and safety between first-line contact aspiration and stent-retriever thrombectomy in stroke patients with large-artery occlusion.
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http://dx.doi.org/10.1177/1591019918821074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547201PMC
June 2019

Development and Validation of a Questionnaire to Assess Barriers to Physical Activity After Stroke: The Barriers to Physical Activity After Stroke Scale.

Arch Phys Med Rehabil 2019 09 24;100(9):1672-1679. Epub 2019 Jan 24.

Service de Médecine Physique et de Réadaptation, CHU de Caen, France; Université de Normandie UNICAEN, INSERM UMR-SU1077, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France.

Objective: To develop and validate a self-reported questionnaire assessing the barriers to physical activity (PA) among stroke survivors.

Design: Psychometric study.

Setting: Ambulatory stroke care.

Participants: A total of one hundred and forty-six (N=146) individuals were included in this study. In stage 1, community-living stroke survivors (n=37; 13 women) with low-moderate disability (modified Rankin Score 0-3, stroke >3mo) were included. In stage 2, participants (n=109; 40 women) with same characteristics were included. Nine professionals experienced in PA for poststroke patients formed an expert panel.

Interventions: In stage 1, semistructured interviews identified perceived barriers to PA, which were then selected by the expert panel and grouped on a Barriers to Physical Activity After Stroke (BAPAS) scale. In stage 2, stroke participants completed a personal information questionnaire and the BAPAS scale.

Main Outcome Measures: An item selection process with factor analysis was carried out. The suitability of the data set was analyzed using the Kaiser-Meyer-Olkin coefficient, internal consistency was evaluated by Cronbach α, and concurrent validity was assessed with Spearman correlation coefficients between the BAPAS scale and the modified Rankin Scale. Test-retest repeatability was estimated using 2-way random effects intraclass correlation coefficient model 2,1 at 4-6 day follow-up (n=21).

Results: Factor analysis supported a 14-item BAPAS that explained 62% of total variance (Kaiser-Meyer-Olkin=0.82) and total score calculated higher than 70 (higher scores for higher barriers). Cronbach α was 0.86, Spearman correlation with the modified Rankin Scale was r=0.65 (P<.001), and test-retest intraclass correlation coefficient was 0.91 (95% CI, 0.79-0.97). The BAPAS scores were higher in patients with greater disabilities and in those with a longer time since the stroke event (P<.01).

Conclusion: We developed and validated the BAPAS scale to assess barriers to PA in stroke survivors with low-moderate disability with promising psychometric properties.
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http://dx.doi.org/10.1016/j.apmr.2018.12.034DOI Listing
September 2019

Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke.

Stroke 2019 02;50(2):298-304

Center for Genomic Medicine (J.R.), Massachusetts General Hospital, Boston.

Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
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http://dx.doi.org/10.1161/STROKEAHA.118.021856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441497PMC
February 2019

First International Consensus on the diagnosis and management of fibromuscular dysplasia.

Vasc Med 2019 04 16;24(2):164-189. Epub 2019 Jan 16.

6 Paris Descartes University, Paris, France.

This article is a comprehensive document on the diagnosis and management of fibromuscular dysplasia (FMD), which was commissioned by the working group 'Hypertension and the Kidney' of the European Society of Hypertension (ESH) and the Society for Vascular Medicine (SVM). This document updates previous consensus documents/scientific statements on FMD published in 2014 with full harmonization of the position of European and US experts. In addition to practical consensus-based clinical recommendations, including a consensus protocol for catheter-based angiography and percutaneous angioplasty for renal FMD, the document also includes the first analysis of the European/International FMD Registry and provides updated data from the US Registry for FMD. Finally, it provides insights on ongoing research programs and proposes future research directions for understanding this multifaceted arterial disease.
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http://dx.doi.org/10.1177/1358863X18821816DOI Listing
April 2019

First international consensus on the diagnosis and management of fibromuscular dysplasia.

J Hypertens 2019 02;37(2):229-252

Paris Descartes University.

This article is a comprehensive document on the diagnosis and management of fibromuscular dysplasia (FMD) which was commissioned by the Working Group 'Hypertension and the Kidney' of the European Society of Hypertension (ESH) and the Society for Vascular Medicine (SVM). This document updates previous consensus documents/scientific statements on FMD published in 2014 with full harmonization of the position of European and US experts. In addition to practical consensus-based clinical recommendations, including a consensus protocol for catheter-based angiography and percutaneous angioplasty for renal FMD, the document also includes the first analysis of the European/International FMD Registry and provides updated data from the US Registry for FMD. Finally, it provides insights on ongoing research programs and proposes future research directions for understanding this multifaceted arterial disease.
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http://dx.doi.org/10.1097/HJH.0000000000002019DOI Listing
February 2019

Diffusion-Weighted Imaging Hyperintensities in Subtypes of Acute Intracerebral Hemorrhage.

Stroke 2018 Dec 7:STROKEAHA118021407. Epub 2018 Dec 7.

From the Normandie University, UNICAEN, Inserm U1237, Caen, France (M.B., M.Z., E.T.).

Background and Purpose- Diffusion-weighted imaging (DWI) hyperintensities in intracerebral hemorrhage (ICH) are associated with increased risk of recurrent ICH, cognitive impairment, and death, but whether these lesions are specific to a subtype of ICH remains uncertain. We investigated the association between DWI lesions and ICH subtype and explored the risk factors for DWI lesions. Methods- In a systematic review of ICH studies, we identified those reporting prevalence of DWI lesions. Two reviewers independently assessed study eligibility and risk of bias and collected data. We determined the pooled prevalence of DWI lesions within 90 days after ICH onset for cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH using random-effects meta-analysis. We calculated odds ratios to compare prevalence of DWI lesions by ICH subtype and to assess risk factors for DWI lesions. Results- Eleven studies (1910 patients) were included. The pooled prevalence of DWI lesions was 18.9% (95% CI, 11.1-26.7) in cerebral amyloid angiopathy- and 21.0% (95% CI, 15.3-26.6) in hypertensive angiopathy-related ICH. There was no difference in the prevalence of DWI lesions between cerebral amyloid angiopathy- (64/292 [21.9%]) and hypertensive angiopathy-related ICH (79/370 [21.4%]; odds ratio, 1.25; 95% CI, 0.73-2.15) in the 5 studies reporting data on both ICH pathogeneses. In all ICH, presence of DWI lesions was associated with neuroimaging features of microangiopathy (leukoaraiosis extension, previous ICH, and presence, and number of microbleeds) but not with vascular risk factors or the use of antithrombotic therapies. Conclusions- Prevalence of DWI lesions in acute ICH averages 20%, with no difference between cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH. Detection of DWI lesions may add valuable information to assess the progression of the underlying microangiopathy.
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http://dx.doi.org/10.1161/STROKEAHA.118.021407DOI Listing
December 2018

Fibromuscular Dysplasia and Its Neurologic Manifestations: A Systematic Review.

JAMA Neurol 2019 02;76(2):217-226

Paris-Descartes University, Institut National de la Santé et de la Recherche Médicale UMR970, Assistance-Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, Paris, France.

Importance: Data on neurologic manifestations of fibromuscular dysplasia (FMD) are rare, and current knowledge remains limited.

Objectives: To present a comprehensive review of the epidemiologic characteristics, management, and prognosis of the neurologic manifestations associated with cerebrovascular FMD (ie, involving cervical or intracranial arteries) and to guide future research priorities.

Evidence Review: References were identified through searches of PubMed from inception to December 2017 using both the medical subject headings and text words. Additional sources were also identified by reviewing reference lists of relevant articles and through searches of the authors' personal files. Selected articles described at least 1 clinical or radiologic feature and/or outcome of cerebrovascular FMD. Isolated case reports could be included if they described interesting or noteworthy manifestations of FMD.

Findings: A total of 84 relevant references were identified. Diagnosis of cerebrovascular FMD is based on the appearance of alternating arterial dilatation and constriction ("string of beads") or of focal narrowing, with no sign of atherosclerotic or inflammatory lesions. Although the diagnosis is easily apparent on results of radiographic imaging, making a diagnosis can be challenging in children or individuals with atypical phenotypes, such as purely intracranial FMD and arterial diaphragm. Involvement of multiple arteries is common, and there is increased incidence of cervical artery dissection and intracranial aneurysms. A variant in the PHACTR1 gene has been associated with FMD as well as cervical artery dissection and migraine, although less than 5% of cases of FMD are familial. Headaches, mainly of the migraine type, are observed in up to 70% of patients with FMD. Cerebrovascular FMD is mostly asymptomatic, but the most frequent neurologic manifestations include transient ischemic attack and ischemic stroke, notably in the presence of associated cervical artery dissection. Other conditions associated with FMD include subarachnoid hemorrhage and, rarely, intracranial hemorrhage. Management relies on observational data and expert opinion. Antiplatelet therapy is considered reasonable to prevent thromboembolic complications. Endovascular therapy is typically restricted to cases with symptomatic stenosis despite optimal medical therapy or in those with rupture of an intracranial aneurysm.

Conclusions And Relevance: Longitudinal cohort studies of individuals of multiple ethnicities with biosampling are needed to better understand the risk factors, pathophysiological features, and outcomes of FMD. Patient advocacy groups could assist researchers in answering patient-centered questions regarding FMD.
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http://dx.doi.org/10.1001/jamaneurol.2018.2848DOI Listing
February 2019

Primary angiitis of the CNS and reversible cerebral vasoconstriction syndrome: A comparative study.

Neurology 2018 10 19;91(16):e1468-e1478. Epub 2018 Sep 19.

From the Department of Internal Medicine (H.d.B., A.A.), Caen University Hospital; University of Caen-Normandie (H.d.B., E.T., A.A); Biostatistics and Clinical Research Unit (J.-J.P.), Caen University Hospital; Emergency Headache Centre (J.M., C.B.), Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris; Department of Neurology (C.A., A.D.), Montpellier University Hospital; Department of Neuroradiology (G.B., O.N.), Sainte-Anne Hospital, Paris-Descartes University; INSERM UMR 894 (O.N.); Department of Vascular Neurology (M.Z.), Saint Joseph Hospital; Université Paris-Descartes (M.Z.), INSERM UMR S 919, Paris; Department of Neurology (E.T.), Caen University Hospital; University of Caen-Normandie (E.T.), INSERM U919; Department of Neurology (M.-G.B.), Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, France; and Division of Rheumatology (C.P.), Vasculitis Clinic, Mount Sinai Hospital, Toronto, Ontario, Canada.

Objectives: To further improve the distinction between primary angiitis of the CNS (PACNS) and reversible cerebral vasoconstriction syndrome (RCVS).

Methods: We compared 2 large French cohorts of patients with PACNS (n = 110, retrospectively and prospectively enrolled) and RCVS (n = 173, prospectively enrolled).

Results: Patients with RCVS were predominantly female ( < 0.0001), with migraines ( < 0.0001), and were more often exposed to vasoactive substances ( < 0.0001) or postpartum ( = 0.002) than patients with PACNS. Headache, especially thunderclap headache, was more frequent in RCVS (both < 0.0001). Thunderclap headache was absent in only 6% of patients with RCVS and was mainly recurrent (87%) and provoked (77%) mostly by sexual intercourse, exertion, or emotion. All other neurologic symptoms (motor deficit, seizure, cognitive disorder, or vigilance impairment, all < 0.0001) were more frequent in PACNS. At admission, brain CT or MRI was abnormal in all patients with PACNS and in 31% of patients with RCVS ( < 0.0001). Acute ischemic stroke was more frequent in PACNS than in RCVS ( < 0.0001). Although intracerebral hemorrhage was more frequent in PACNS ( = 0.006), subarachnoid hemorrhage and vasogenic edema predominated in RCVS ( = 0.04 and = 0.01, respectively). Multiple small deep infarcts, extensive deep white matter lesions, tumor-like lesions, or multiple gadolinium-enhanced lesions were observed only in PACNS, whereas cervical artery dissection was found only in RCVS.

Conclusions: Our study confirms that careful analysis of clinical context, headache features, and patterns of brain lesions can distinguish PACNS and RCVS within the first few days of admission in most cases. However, diagnosis remains challenging in a few cases.
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http://dx.doi.org/10.1212/WNL.0000000000006367DOI Listing
October 2018

Determinants and outcome of multiple and early recurrent cervical artery dissections.

Neurology 2018 08 1;91(8):e769-e780. Epub 2018 Aug 1.

From the Department of Neuro-oncology (A.C.), Netherlands Cancer Institute/Antoni van Leeuwenhoek; Department of Neurology (A.C.), MC Slotervaart, Amsterdam, the Netherlands; University of Bordeaux (S.S., S.D.); Bordeaux Population Health (S.S., S.D.), INSERM Center U1219, France; Department of Neurology (C.J.V., B.G.-S., H.S., S.J., U.F., M.A.), University Hospital Inselspital and University of Bern; Division of Neuropediatrics (B.G.-S.), San Giovanni Hospital Bellinzona, Switzerland; Department of Neurology (T.M.M., T.T.), Helsinki University Central Hospital, Finland; Departments of Neurology and Public Health Sciences (A.S., B.B.W.), University of Virginia, Charlottesville; Department of Clinical and Experimental Sciences (A.P.), Neurology Clinic, University of Brescia, Italy; Department of Neurology (M.K., C.G.-G., C.L.), Heidelberg University Hospital, Germany; Normandie Université (E.T.), Unicaen, CHU Caen, Inserm U1237; Université Paris Descartes (E.T.), CH Ste Anne, Inserm U894, Paris, France; Stroke Division (V.T.), Florey Institute for Neuroscience and Mental Health, University of Melbourne; Department of Neurology (V.T.), Austin Health, Heidelberg, Victoria, Australia; Department of Neurology (Y.B.), Dijon University Hospital; Department of Neurology (P.R., H.C., M.-G.B.), Lariboisière Hospital, Paris 7 University, DHU Neurovasc Sorbonne Paris Cité, France; Cerebrovascular Unit (A.B.), IRCCS Foundation C. Besta Neurological Institute, Milan, Italy; Suva/Swiss National Accident Insurance Fund (T.B.), Lucerne, Switzerland; Stroke Unit and Division of Internal and Cardiovascular Medicine (V.C.), University of Perugia, Italy; Department of Neurology and Stroke Center (P.A.L., C.T., S.T.E.), Department of Clinical Research, University Hospital and University of Basel, Switzerland; Neurology Clinic (C.L.), Memmingen Hospital, Germany; Department of Neurology (J.J.M.), Sanatorio Allende, Cordoba, Argentina; Department of Neurology (D.L.), Lille University, INSERM U1171, France; NeuroCentre (R.W.B.), Clinic Hirslanden Zürich, Switzerland; Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland; INSERM 1176 (J.D.), Institut Pasteur de Lille, France; Department of Clinical Neuroscience (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (T.T.), Sahlgrenska University Hospital, Gothenburg, Sweden; and Department of Neurology-Memory Clinic (S.D.), Bordeaux University Hospital, France.

Objective: To assess putative risk factors and outcome of multiple and early recurrent cervical artery dissection (CeAD).

Methods: We combined data from 2 multicenter cohorts and compared patients with multiple CeAD at initial diagnosis, early recurrent CeAD within 3 to 6 months, and single nonrecurrent CeAD. Putative risk factors, clinical characteristics, functional outcome, and risk of recurrent ischemic events were assessed.

Results: Of 1,958 patients with CeAD (mean ± SD age 44.3 ± 10 years, 43.9% women), 1,588 (81.1%) had single nonrecurrent CeAD, 340 (17.4%) had multiple CeAD, and 30 (1.5%) presented with single CeAD at admission and had early recurrent CeAD. Patients with multiple or early recurrent CeAD did not significantly differ with respect to putative risk factors, clinical presentation, and outcome. In multivariable analyses, patients with multiple or early recurrent CeAD more often had recent infection (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.29-2.53), vertebral artery dissection (OR 1.82, 95% CI 1.34-2.46), family history of stroke (OR 1.55, 95% CI 1.06-2.25), cervical pain (OR 1.36, 95% CI 1.01-1.84), and subarachnoid hemorrhage (OR 2.85, 95% CI 1.01-8.04) at initial presentation compared to patients with single nonrecurrent CeAD. Patients with multiple or early recurrent CeAD also had a higher incidence of cerebral ischemia (hazard ratio 2.77, 95% CI 1.49-5.14) at 3 to 6 months but no difference in functional outcome compared to patients with single nonrecurrent CeAD.

Conclusion: Patients with multiple and early recurrent CeAD share similar risk factors, clinical characteristics, and functional outcome. Compared to patients with single nonrecurrent CeAD, they are more likely to have recurrent cerebral ischemia at 3 to 6 months, possibly reflecting an underlying transient vasculopathy.
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http://dx.doi.org/10.1212/WNL.0000000000006037DOI Listing
August 2018

Treatment and Long-Term Outcomes of Primary Central Nervous System Vasculitis.

Stroke 2018 08;49(8):1946-1952

Vasculitis Clinic, Division of Rheumatology, Mount Sinai Hospital, Toronto (C.P.).

Background and Purpose- We aimed to analyze the long-term outcomes of patients with primary central nervous system vasculitis according to the different therapeutic strategies used to induce remission. Methods- We assessed the rate of prolonged remission (defined by the absence of relapse at ≥12 months after diagnosis) and the functional status at last follow-up in patients with primary central nervous system vasculitis included in the French cohort, who achieved a first remission according to the 3 main groups of treatments administered: glucocorticoids only (group 1); induction treatment with glucocorticoids and an immunosuppressant, but no maintenance (group 2); and combined treatment with glucocorticoids and an immunosuppressant for induction followed by maintenance therapy (group 3). Good functional status was defined as a modified Rankin Scale score ≤2 at the last follow-up. Results- Remission was achieved with the initial induction treatment in 106 (95%) of the 112. Prolonged remission without relapse was observed in 70 (66%) patients after 57 (12-198) months of follow-up. A good functional status at last follow-up (ie, modified Rankin Scale score ≤2) was observed in 63 (56%) patients. Overall mortality was 8%. The initial severity and the radiological presentations were comparable in the 3 treatment groups. More prolonged remissions ( P=0.003) and a better functional status at the last follow-up ( P=0.0004) were observed in group 3. In multivariate analysis, the use of maintenance therapy was associated with prolonged remission (odds ratio, 4.32 [1.67-12.19]; P=0.002) and better functional status (odds ratio, 8.09 [3.24-22.38]; P<0.0001). Conclusions- This study suggests that maintenance therapy with an immunosuppressant combined with glucocorticoids lead to the best long-term clinical and functional outcomes in patients with primary central nervous system vasculitis after having achieved remission with either glucocorticoids alone or in combination with another immunosuppressant.
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http://dx.doi.org/10.1161/STROKEAHA.118.021878DOI Listing
August 2018

Office white-coat effect tail and long-term cardiovascular risks in the Gubbio residential cohort study.

J Hypertens 2018 09;36(9):1825-1832

EA 4650, Signalisation, électrophysiologie et imagerie des lésions d'ischémie reperfusion myocardique.

Objective: The aim was to investigate whether office white-coat effect tail (OWCET), the waning of blood pressure (BP) after its waxing during office visit, predicted long-term major fatal and nonfatal events in the Gubbio residential cohort.

Methods: There were 3572 persons (44% men, 54 ± 11 years old) included. OWCET was defined as a decrease of 10 mmHg or more in SBP between the third and first measurement out of a series obtained a few min apart in which the second and third were considered actual baseline SBP at enrollment. Cardiovascular (CVD), including strokes and coronary heart disease (CHD) hard criteria incidences and deaths along with all-cause deaths were considered.

Results: Over 185 months median follow-up, individuals with OWCET had significantly higher risk factors except for smoking, which was less frequent. OWCET was associated with an increased risk of both CVD [HR 1.25 (95% CI 1.02-1.52)] and CHD [HR 1.35 (95% CI 1.01-1.80)] events independently of traditional risk factors (age, sex, total cholesterol, HDL, cigarettes and BMI) including SBP. When effective antihypertensive treatment was considered, there was a significant higher CVD risk in individuals with OWCET (P < 0.037). In uncontrolled or untreated individuals, those with OWCET also had a higher risk (P < 0.073).

Conclusion: In primary care, OWCET should be searched for as it can improve stratification of long-term CVD-CHD risks.
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http://dx.doi.org/10.1097/HJH.0000000000001807DOI Listing
September 2018

University education and cervical artery dissection.

J Neurol 2018 May 24;265(5):1065-1070. Epub 2018 Feb 24.

Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

Background And Purpose: We investigated whether university education is more likely in cervical artery dissection (CeAD)-patients than in age- and sex-matched patients with ischemic stroke (IS) due to other causes (non-CeAD-IS-patients).

Methods: Patients from the Cervical Artery Dissection and Ischemic Stroke Patients study with documented self-reported profession before onset of IS due to CeAD (n = 715) or non-CeAD causes (n = 631) were analyzed. In the reported profession, the absence or presence of university education was assessed. Professions could be rated as academic or non-academic in 518 CeAD and 456 non-CeAD patients. Clinical outcome at 3 months was defined as excellent if modified Rankin Scale was 0-1.

Results: University education was more frequent in CeAD-patients (100 of 518, 19.3%) than in non-CeAD-IS-patients (61 of 456, 13.4%, p = 0.008). CeAD-patients with and without university education differed significantly with regard to smoking (39 vs. 57%, p = 0.001) and excellent outcome (80 vs. 66%, p = 0.004). In logistic regression analysis, university education was associated with excellent outcome in CeAD-patients (OR 2.44, 95% CI 1.37-5.38) independent of other outcome predictors such as age (OR 0.97, 95% CI 0.84-0.99), NIHSS (OR 0.80, 95% CI 0.76-0.84) and local signs (OR 2.77, 95% CI 1.37-5.57).

Conclusion: We observed a higher rate of university education in patients with CeAD compared with non-CeAD patients in our study population. University education was associated with favorable outcome in CeAD-patients. The mechanism behind this association remains unclear.
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http://dx.doi.org/10.1007/s00415-018-8798-7DOI Listing
May 2018

Long-Term Risk of Myocardial Infarction Compared to Recurrent Stroke After Transient Ischemic Attack and Ischemic Stroke: Systematic Review and Meta-Analysis.

J Am Heart Assoc 2018 01 18;7(2). Epub 2018 Jan 18.

Normandie Université UNICAEN, Inserm U1237 CHU Caen, Caen, France

Background: Uncertainties remain about the current risk of myocardial infarction (MI) after ischemic stroke or transient ischemic attack.

Methods And Results: We undertook a systematic review to estimate the long-term risk of MI, compared to recurrent stroke, with temporal trends in ischemic stroke/transient ischemic attack patients. Annual risks and 95% confidence intervals (95% CI) of MI and recurrent stroke were estimated using random-effect meta-analyses. We calculated incidence ratios of MI/recurrent stroke, for fatal and nonfatal events, using similar analyses. Rate ratios for MI in patients with potential risk factors compared to those without were calculated using Poisson regression.A total of 58 studies (131 299 patients) with a mean (range) follow-up of 3.5 (1.0-10.0) years were included. The risk of MI was 1.67%/y (95% CI 1.36-1.98, <0.001 for heterogeneity) and decreased over time (=0.021); 96% of the heterogeneity between studies was explained by study design, study period, follow-up duration, mean age, proportion of patients on antithrombotic therapy, and incident versus combined ischemic stroke/transient ischemic attack. The risk of recurrent stroke was 4.26%/y (95% CI 3.43-5.09, <0.001), with no change over time (=0.63). The risk of fatal MI was half the risk of recurrent strokes ending in fatality (incidence ratio=0.51, 95% CI 0.14-0.89, =0.58). The risk of nonfatal MI was 75% smaller than the risk of recurrent nonfatal stroke (incidence ratio=0.25, 95%CI 0.02-0.50, =0.68). Male sex, hypertension, coronary and peripheral artery diseases were associated with a doubled risk of MI.

Conclusions: After ischemic stroke/transient ischemic attack, the risk of MI is currently <2%/y, and recurrent stroke is a more common cause of death than MI.
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http://dx.doi.org/10.1161/JAHA.117.007267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850155PMC
January 2018

Apixaban in the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in France: Rationale and design of the PAROS cross-sectional study.

Arch Cardiovasc Dis 2018 May 27;111(5):349-356. Epub 2017 Nov 27.

Department of cardiology, hôpital Bichat, AP-HP, Paris, France; FACT, DHU FIRE, Inserm U-1148, LVTS, université Paris-Diderot, Paris, France; Imperial College, Royal Brompton Hospital, London, United Kingdom. Electronic address:

Background: Atrial fibrillation (AF) is the most common arrhythmia worldwide, and its prevalence is expected to increase with population ageing. The use of vitamin K antagonists (VKAs) for the prevention of stroke and/or systemic embolism in patients with non-valvular atrial fibrillation (NVAF) was recently challenged by non-VKA oral anticoagulants (NOACs), demonstrating a favourable risk-benefit profile, with reductions in stroke, intracranial haemorrhage and mortality, similar major bleeding, but increased gastrointestinal bleeding. Nevertheless, data on their use in a "real-life" setting are scarce for France.

Aims: To compare the characteristics of patients with AF newly anticoagulated with either VKAs or NOACs, to describe the reasons for discontinuing the previous anticoagulant strategy and/or choosing the newly initiated anticoagulant treatment, and to precisely describe the prescriptions of patients newly initiated with apixaban.

Methods: This is a nationwide multicentre non-interventional cross-sectional study conducted in patients with AF by a representative stratified sample of cardiologists in France. Over a 12-month accrual period, consecutive patients aged ≥18 years with NVAF, for whom anticoagulant treatment (VKAs or NOACs) has been initiated within the last three months before the index consultation, will be included. The primary outcome will be the comparison of anticoagulant-naïve patient characteristics, co-morbidities and treatment history among the anticoagulant subgroups. Secondary endpoints will include a description of the reasons for discontinuing the previous anticoagulant strategy and/or for initiating and choosing the newly initiated anticoagulant treatment, as well as the prescription conditions of apixaban.

Conclusion: The PAROS study will provide real-life data on the characteristics of NVAF patients and their anticoagulant prescription in France.
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http://dx.doi.org/10.1016/j.acvd.2017.07.005DOI Listing
May 2018

Some concepts in stroke

Rev Prat 2017 Nov;67(9):e467

Université Caen-Basse-Normandie, service de neurologie vasculaire, CHU Caen (SG, ET), université Rennes-1, service de radiologie, unité d’imagerie neurofaciale, CHU Rennes (JYG, HR), France

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November 2017

Vascular Tissue-Type Plasminogen Activator Promotes Intracranial Aneurysm Formation.

Stroke 2017 09 28;48(9):2574-2582. Epub 2017 Jul 28.

From the Department of Physiopathology and Imaging of Neurological Disorders, INSERM U1237, UNICAEN, GIP Cyceron, France (P.-E.L., R.G., S.M.d.L., M.H., M.G., E.M., B.D., E.T., P.C., D.V., C.O.); Department of Interventional Neuroradiology (P.-E.L., B.G., F.T.) and Department of Neurosurgery (F.S.), Hôpital Wertheimer, University Lyon 1, Bron, France; and Department of Neurology (E.T.), Department of Neuroradiology (P.C.), and Department of Clinical Research (D.V.), CHU Caen, University Caen Normandie, France.

Background And Purpose: Although the mechanisms that contribute to intracranial aneurysm (IA) formation and rupture are not totally elucidated, inflammation and matrix remodeling are incriminated. Because tPA (tissue-type plasminogen activator) controls both inflammatory and matrix remodeling processes, we hypothesized that tPA could be involved in the pathophysiology of IA.

Methods: Immunofluorescence analyses of tPA and its main substrate within the aneurysmal wall of murine and human samples were performed. We then compared the formation and rupture of IAs in wild-type, tPA-deficient and type 1 plasminogen activator inhibitor-deficient mice subjected to a model of elastase-induced IA. The specific contribution of vascular versus global tPA was investigated by performing hepatic hydrodynamic transfection of a cDNA encoding for tPA in tPA-deficient mice. The formation and rupture of IAs were monitored by magnetic resonance imaging tracking for 28 days.

Results: Immunofluorescence revealed increased expression of tPA within the aneurysmal wall. The number of aneurysms and their symptomatic ruptures were significantly lower in tPA-deficient than in wild-type mice. Conversely, they were higher in plasminogen activator inhibitor-deficient mice. The wild-type phenotype could be restored in tPA-deficient mice by selectively increasing circulating levels of tPA via hepatic hydrodynamic transfection of a cDNA encoding for tPA.

Conclusions: Altogether, this preclinical study demonstrates that the tPA present in the blood stream is a key player of the formation of IAs. Thus, tPA should be considered as a possible new target for the prevention of IAs formation and rupture.
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http://dx.doi.org/10.1161/STROKEAHA.117.017305DOI Listing
September 2017

High Prevalence of Multiple Arterial Bed Lesions in Patients With Fibromuscular Dysplasia: The ARCADIA Registry (Assessment of Renal and Cervical Artery Dysplasia).

Hypertension 2017 09 17;70(3):652-658. Epub 2017 Jul 17.

Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B., O.O.), Department of Radiology (F.T.), and INSERM U1039 (J.-P.B.), France; Hypertension Unit, CHU Timone, Marseille, France (F.S.); Department of Radiology, CHU Gabriel-Montpied, Clermont-Ferrand, France (L.B.); Hypertension Unit, CHU Rangueil, Toulouse, France (B.B.); Hypertension Unit, Hôpital Cardiologique, Lille, France (C.M.-V.); Normandie Université, University of Caen Normandy, INSERM U919, CHU de Caen, Unité Neurovasculaire, France (E.T.); Department of Vascular Medicine (C.L.H.), Caen, France; Hôpital Saint André, Bordeaux, France (P.G.); Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P.); Division of Cardiology (A.P.) and Division of Radiology (F.H.), Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Fibromuscular dysplasia (FMD) commonly affects the renal and cervical arteries but has been described to affect other vascular beds as well. The prevalence of and clinical characteristics associated with multisite FMD (string-of-beds or focal stenoses affecting at least 2 vascular beds) are not known. In the prospective ARCADIA registry (Assessment of Renal and Cervical Artery Dysplasia), symptomatic patients with renal artery (RA) FMD underwent tomographic- or magnetic resonance-angiography from the aortic arch to the intracranial arteries and those with cervical FMD from the diaphragm to the pelvis. Of 469 patients (84.0% women), 225 (48.0%) had multisite FMD. In addition, 86 of 244 patients with single-site disease had dissections or aneurisms affecting other vascular beds, totaling 311 patients (66.3%) with lesions in >1 vascular bed. Among patients with a cerebrovascular presentation, the prevalence of RA lesions was higher in patients with than in those without hypertension (odds ratio, 3.4; 95% confidence interval, 1.99-6.15). Among patients with a renal presentation, the prevalence of cervical lesions was higher in patients with bilateral than in those with unilateral RA lesions (odds ratio, 1.9; 95% confidence interval, 0.99-3.57). In conclusion, FMD is a systemic arterial disease. At least 2 vascular beds were affected by dysplastic stenoses in 48.0% of cases and by dysplastic stenoses, aneurysms, and dissections in 66.1% of cases. RA imaging should be proposed to hypertensive patients with a cerebrovascular presentation. Cervical artery imaging should be considered in patients with a renal presentation and bilateral RA lesions.

Clinical Trial Registration: URL: www.Clinicaltrials.gov. Unique identifier: NCT02884141.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09539DOI Listing
September 2017