Autosomal-dominant familial hematuria with retinal arteriolar tortuosity and contractures: A novel syndrome

Autosomal-dominant familial hematuria with retinal arteriolar tortuosity and contractures: A novel syndrome.BackgroundAutosomal-dominant forms of hematuria have been mostly related to mutations in the COL4A3/COL4A4 genes. Patients with thin basement membrane (BM) disease do not have extrarenal manifestations, while those with Alport syndrome often present with hearing loss, anterior lenticonus, and dot-and-fleck retinopathy.MethodsWe performed a phenotypic study and a candidate gene approach in a four-generation family presenting with autosomal-dominant hematuria associated with extrarenal manifestations. Renal biopsy was analyzed for determination of BM thickness and expression of chains of type IV collagen. Linkage to 18 candidate genes/loci was investigated using polymorphic microsatellite markers.ResultsIn all affected patients, hematuria without proteinuria was associated with muscular contractures and retinal arterial tortuosities responsible for retinal hemorrhages. Cardiac arrythmia, Raynaud phenomena, and brain MRI abnormalities were also observed. Despite the presence of red cells in tubule sections, no glomerular abnormalities were found by electron microscopy. Expression of type IV collagen chains and glomerular BM thickness was normal. We searched for a molecular defect affecting either BM or angiogenesis. Linkage analyses of genes encoding BM components (COL4A3/COL4A4, COL6A1, COL6A2, COL6A3, FBLN1), and angiogenic factors or their receptors (VHL, ANPT1, ANPT2, TIE, TEK, NOTCH2, NOTCH3, NOTCH4, DLL4, JAG1, JAG2) and of the facio-sapulo-humeral dystrophy and 3q21 loci failed to show segregation of the disease with those gene loci.ConclusionWe have identified a new inherited hematuria syndrome associated with retinal vessel tortuosities and contractures. We recommend performing a fundus examination in patients with familial hematuria and episodes of visual impairment, as well as a urinary analysis in patients with retinal arterial tortuosity or congenital muscular contractures

Prise en charge des accidents vasculaires cérébraux (évaluation d'une unité neuro-vasculaire et de sa filière)

Les unités neuro-vasculaires (UNV) ont montré leur efficacité dans le traitement des accidents vasculaires cérébraux (AVC) en réduisant les complications et la dépendance. Notre objectif a été de décrire le profil des patients hospitalisés dans une UNV et le fonctionnement de cette unité au sein d'une filière de soins. Cette étude rétrospective porte sur les patients hospitalisés pour AVC dans l'UNV de l'hôpital Tenon en 2001. Sur 410 patients admis en urgence dans l'UNV, 85,9 % (352) avaient un AVC (âge moyen : 65,2 ans ; 55,7 % d'hommes). Parmi eux, 74,5 % ont été hospitalisés via la filière identifiée d'amont. La majorité venait des urgences de Tenon, aucun patient n'est arrivé par le SAMU. Seuls 42,8 % ont été admis dans l'unité dans les 24h suivant la constatation de l'AVC. Les AVC étaient plus souvent ischémiques (89,8 %) qu'hémorragiques (10,2 %). Le NIHSS moyen était à 5. La durée moyenne de séjour (DMS) était de 14,3 jours. La DMS était significativement influencée par un âge > 70 ans, le type d'AVC (AIT : 8,9 jours ; infarctus : 14,9 jours ; hémorragie : 18,6 jours), la sévérité de l'AVC (27,5 jours pour un NIHSS entre 10 et 21 ; 10,7 jours pour un NIHSS entre 0 et 3), l'existence de comorbidités, la survenue de complications. Le taux de mortalité (3,4 %) et de complications (6,5 %) étaient faibles. A la fin de l'hospitalisation, 56,5 % des patients ont regagné leur domicile. Parmi les patients transférés en soins de suite, 75,6 % l'ont été dans des établissements de la filière identifiée d'aval. Ces résultats montrent une bonne articulation entre l'UNV et les filières d'aval. Ils soulignent la nécessité d'améliorer les délais d'arrivée des patients et donc la filière d'amont. Ceci passe par une meilleure éducation des patients, des médecins, une coopération avec le SAMU, et une amélioration du circuit intra-hospitalier.PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation à long terme des corrélations et de l'évolution des échelles neurologiques après un accident vasculaire cérébral

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications

International audienceCerebral amyloid angiopathy (CAA) corresponds to the deposition of amyloid material in the cerebral vasculature, leading to structural modifications of blood vessel walls. The most frequent form of sporadic CAA involves fibrillar β-amyloid peptide (Aβ) deposits, mainly the 40 amino acid form (Aβ1-40), which are commonly found in the elderly with or without Alzheimer's disease. Sporadic CAA usually remains clinically silent. However, in some cases, acute complications either hemorrhagic or inflammatory can occur. Similar complications occurred after active or passive immunization against Aβ in experimental animal models exhibiting CAA, and in subjects with Alzheimer's disease during clinical trials. The triggering of these adverse events by active immunization and monoclonal antibody administration in CAA-bearing individuals suggests that analogous mechanisms could be involved during spontaneous CAA complications, drawing particular attention to the role of anti-Aβ antibodies. However, antibodies that react with several monomeric and aggregated forms of Aβ spontaneously occur in virtually all human individuals, hence being part of the "natural antibody" repertoire. Natural antibodies are usually described as having low-affinity and high cross-reactivity toward microbial components and autoantigens. Although frequently of the IgM class, they also belong to IgG and IgA isotypes. They likely display homeostatic functions and protective roles in aging. Until recently, the peculiar properties of these natural antibodies have hindered proper analysis of the Aβ-reactive antibody repertoire and the study of their implication in CAA complications. Herein, we review and comment the evidences of an auto-immune nature of spontaneous CAA complications, and discuss implications for forthcoming research and clinical practice

Very early neurologic improvement after intravenous thrombolysis.

International audienceOBJECTIVE: To evaluate whether very early neurologic improvement (VENI) after intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) perfusion in patients with acute ischemic stroke (AIS) predicts favorable outcome at 3 months. DESIGN: Retrospective analysis of prospective data. SETTING: Stroke registry at the Stroke Unit, Tenon University Hospital. PATIENTS: We analyzed consecutive patients with AIS treated with i.v. rt-PA between November 11, 2002, and December 24, 2007. MAIN OUTCOME MEASURES: VENI at 1 hour was defined as a National Institute of Health Stroke Scale score of 0 at the end of rt-PA perfusion or an improvement of 5 or more points compared with baseline. Favorable outcome was defined as a modified Rankin Scale score of 1 or less at 3 months. RESULTS: Of 120 patients with AIS treated with i.v. rt-PA, 22 (18.3%) had VENI after i.v. rt-PA perfusion. Favorable outcome was observed in 15 patients with VENI (68.2%) and in 29 patients without VENI (29.6%) (P < .001). No symptomatic intracerebral hemorrhage occurred in patients with VENI. Mortality rates were 0% in the patients with VENI and 17.3% in patients without VENI. Baseline scores for VENI (adjusted odds ratio, 6.23; 95% confidence interval, 2.03-19.13; P = .001) and the National Institute of Health Stroke Scale (0.83; 0.76-0.91; P < .001) were the only 2 factors associated with favorable outcome (modified Rankin Scale score of ≤1). CONCLUSIONS: VENI at the end of i.v. rt-PA perfusion in patients with AIS independently predicts favorable outcome at 3 months

Three-dimensional transesophageal echocardiography for descending aortic atheroma: a preliminary study

International audienceTransesophageal echocardiography (TEE) is an efficient method for characterization of aortic atherosclerotic plaques (AAP). The aim of our study was to evaluate the feasibility and the additional contribution of three-dimensional (3D) TEE in the evaluation of AAPs in descending thoracic aorta. We studied 82 patients referred for TEE regardless of the indication. All patients underwent two-dimensional (2D) conventional acquisitions. A 3D TEE study was performed for all AAPs localized in the descending thoracic aorta. Thickness, degree of calcification, the presence of ulceration or mobile debris were compared for 2D and 3D modes. From 3D data, three types of AAPs were defined according to their morphological characteristics (surface and contours). Among 192 AAPs found on 2D acquisition, 189 (98.4 %) were also identified by 3D TEE. For AAP characterization, agreement was good between 2D TEE and 2D extracted from 3D with the multiplanar reconstruction mode: 83.6 % (k = 0.69) for thickness and 82.5 % (k = 0.72) for degree of calcification. All AAPs ulcerations (n = 13) and mobile debris (n = 3) seen in 2D were identified in 3D. 2D characteristics of the 3D AAPs' morphological types were different: type I plaques were thin and rarely calcified; type III plaques were thicker and often calcified; and type II presented intermediate characteristics. There was overlap among groups and the 3D morphology could not be predicted from 2D data. 3D TEE is a feasible method for the analysis of AAPs. In addition to conventional characterization, 3D TEE provides a new morphological approach to AAPs

Echocardiographic features in antiphospholipid-negative Sneddon's syndrome and potential association with severity of neurological symptoms or recurrence of strokes: a longitudinal cohort study

Aims: Sneddon's syndrome (SS) may be classified as antiphospholipid positive (aPL+) or negative (aPL- SS). An association between Libman-Sacks (LS) endocarditis and strokes has been described in aPL+ patients. To describe cardiac involvement in aPL- SS and assess the potential association between LS endocarditis and severity or recurrence of neurological symptoms.Methods and results: This longitudinal cohort study included aPL- SS patients followed in our departments between 1991 and June 2018. All patients underwent transthoracic 2D and Doppler echocardiography at diagnosis. Follow-up echocardiography was performed annually and the potential relationship between LS endocarditis development and neurovascular relapse as well as long-term cardiac worsening was prospectively assessed. We included 61 patients [52 women; median age 45 (range 24-60)]. For valvular involvement, 36 (59%) patients showed leaflet thickening; 18 (29.5%) had LS endocarditis at baseline. During a median follow-up of 72 months, LS endocarditis developed in eight (17.4%) patients, and 13 (28.3%) showed significant worsening of their cardiac status, including two who needed valvular replacement. After adjusting for baseline antithrombotic treatment regimen, neither the presence of LS endocarditis at baseline nor development during follow-up was associated with neurological relapse [hazard ratio (HR): 1.06, 95% confidence interval (CI): 0.33-4.74, P = 0.92] and [HR: 0.38, 95% CI: 0.02-1.89, P = 0.31], respectively.Conclusion: A long-term follow-up is needed to detect cardiac complications in aPL- SS. No change in neurological relapse was observed in patients presenting LS endocarditis occurrence during follow-up without any modification in antithrombotic treatment. Further research is necessary to assess the usefulness of treatment escalation in these patients. </p

Persistent perfusion abnormalities at day 1 correspond to different clinical trajectories after stroke

International audienceBackground Perfusion abnormalities after thrombolysis are frequent within and surrounding ischemic lesions, but their relative frequency is not well known. Objective To describe the different patterns of perfusion abnormalities observed at 24 hours and compare the characteristics of the patients according to their perfusion pattern. Methods From our thrombolysis registry, we included 226 consecutive patients with an available arterial spin labeling (ASL) perfusion sequence at day 1. We performed a blinded assessment of the perfusion status (hypoperfusion-h, hyperperfusion-H, or normal-N) in the ischemic lesion and in the surrounding tissue. We compared the time course of clinical recovery, the rate of arterial recanalization, and hemorrhagic transformations in the different perfusion profiles. Results We identified seven different perfusion profiles at day 1. Four of these (h/h, h/H, H/H, and H/N) represented the majority of the population (84.1%). The H/H profile was the most frequent (34.5%) and associated with 3-month good outcome (modified Rankin Scale (mRS): 63.5%). Patients with persistent hypoperfusion within and outside the lesion (h/h, 12.4%) exhibited worse outcomes after treatment (mRS score 0–2: 23.8%) than other patients, were less frequently recanalized (40.7%), and had more parenchymal hematoma (17.8%). The h/H profile had an intermediate clinical trajectory between the h/h profile and the hyperperfused profiles. Conclusion ASL hypoperfusion within the infarct and the surrounding tissue was associated with poor outcome. A more comprehensive view of the mechanisms in the hypoperfused surrounding tissue could help to design new therapeutic approaches during and after reperfusion therapies

European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke

Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischaemic stroke (AIS) patients with a non-inferiority design for three of them. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted according to ESO standard operating procedure based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We identified three relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews of the literature and meta-analyses, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert consensus statements were provided if insufficient evidence was available to provide recommendations based on the GRADE approach. For patients with AIS of &lt;4.5 h duration who are eligible for IVT, tenecteplase 0.25 mg/kg can be used as a safe and effective alternative to alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS of &lt;4.5 h duration who are eligible for IVT, we recommend against using tenecteplase at a dose of 0.40 mg/kg (low evidence, strong recommendation). For patients with AIS of &lt;4.5 h duration with prehospital management with a mobile stroke unit who are eligible for IVT, we suggest tenecteplase 0.25 mg/kg over alteplase 0.90 mg/kg (low evidence, weak recommendation). For patients with large vessel occlusion (LVO) AIS of &lt;4.5 h duration who are eligible for IVT, we recommend tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS on awakening from sleep or AIS of unknown onset who are selected with non-contrast CT, we recommend against IVT with tenecteplase 0.25 mg/kg (low evidence, strong recommendation). Expert consensus statements are also provided. Tenecteplase 0.25 mg/kg may be favoured over alteplase 0.9 mg/kg for patients with AIS of &lt;4.5 h duration in view of comparable safety and efficacy data and easier administration. For patients with LVO AIS of &lt;4.5 h duration who are IVT-eligible, IVT with tenecteplase 0.25 mg/kg is preferable over skipping IVT before MT, even in the setting of a direct admission to a thrombectomy-capable centre. IVT with tenecteplase 0.25 mg/kg may be a reasonable alternative to alteplase 0.9 mg/kg for patients with AIS on awakening from sleep or AIS of unknown onset and who are IVT-eligible after selection with advanced imaging

Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: Insights from the TETRIS registry

International audienceIntroduction: The encouraging efficacy and safety data on intravenous thrombolysis with tenecteplase in ischemic stroke and its practical advantages motivated our centers to switch from alteplase to tenecteplase. We report its impact on treatment times and clinical outcomes. Methods: We retrospectively analyzed clinical and procedural data of patients treated with alteplase or tenecteplase in a comprehensive (CSC) and a primary stroke center (PSC), which transitioned respectively in 2019 and 2018. Tenecteplase enabled in-imaging thrombolysis in the CSC. The main outcomes were the imaging-to-thrombolysis and thrombolysis-to-puncture times. We assessed the association of tenecteplase with 3-month functional independence and parenchymal hemorrhage (PH) with multivariable logistic models. Results: We included 795 patients, 387 (48.7%) received alteplase and 408 (51.3%) tenecteplase. Both groups (tenecteplase vs alteplase) were similar in terms of age (75 vs 76 years), baseline NIHSS score (7 vs 7.5) and proportion of patients treated with mechanical thrombectomy (24.1% vs 27.5%). Tenecteplase patients had shorter imaging-to-thrombolysis times (27 vs 36 min, p < 0.0001) mainly driven by patients treated in the CSC (22 vs 38 min, p < 0.001). In the PSC, tenecteplase patients had shorter thrombolysis-to-puncture times (84 vs 95 min, p = 0.02), reflecting faster interhospital transfer for MT. 3-month functional independence rate was higher in the tenecteplase group (62.8% vs 53.4%, p < 0.01). In the multivariable analysis, tenecteplase was significantly associated with functional independence (OR a 1.68, 95% CI 1.15–2.48, p < 0.01), but not with PH (OR a 0.68, 95% CI 0.41–1.12, p = 0.13). Conclusion: Switch from alteplase to tenecteplase reduced process times and may improve functional outcome, with similar safety profile