Factors associated with patent foramen ovale-related stroke: SAFAS study.

BACKGROUND: Persistent foramen ovale (PFO) contributes to cryptogenic stroke and is associated with stroke recurrence, although the exact mechanism of ischemic events is not fully understood. Several biomarkers have been developed for the prediction of atrial fibrillation after stroke, but there are currently only limited data on their potential value for the diagnosis of PFO-related stroke. METHODS: This study was a prospective single-center study that included all patients hospitalized between March 31, 2018, and January 18, 2020, in the stroke department of the Dijon University Hospital for ischemic stroke without obvious cause and without a history of atrial fibrillation. PFO was systematically screened by transthoracic echocardiography and images were reviewed by an independent cardiologist blinded from clinical data. PFO was defined according to the CLOSE trial criteria: PFO associated with interatrial septal aneurysm or significant interatrial shunt (> 30 microbubbles in the left atrium within three cardiac cycles after right atrial opacification). The potential association of PFO-related stroke with biomarkers of cardiac fibrosis and inflammation such as galectin-3, GDF-15, ST-2, osteoprotegerin and NT-proBNP was tested using multivariate backward stepwise logistic regression. RESULTS: Of the 240 patients included in the SAFAS study, 229 had complete echocardiographic data, and 23 (10%) had PFO-related stroke. Patients with PFO-related stroke were significantly younger (58±14 vs. 69±14, P<0.001), had less frequent previous arterial hypertension (30 vs. 60%, P=0.008), and more frequent cerebellar territory involvement (26 vs. 9%, P=0.014) compared to the other patients. In addition, they had less frequently left atrial dilatation (left atrial index volume>34mL/m2 [9 vs. 35%, P=0.009]). After ROC curve analysis for definition of thresholds, PFO-related stroke patients more often had galectin-3<9.5ng/mL (59 vs. 27%, P=0.002), ST2<13380pg/ml (23 vs. 50%, P=0.007), GDF-15<1200ng/mL (59 vs. 27%, P=0.002), osteoprotegerin<1133pg/mL (82 vs. 58%, P=0.033) and NT-proBNP<300pg/mL (88 vs. 55%, P=0.009). After multivariate analysis, only galectin-3<9.5ng/mL (OR [95% CI] 3.4 [1.18; 9.8], P=0.024) and osteoprotegerin<1133pg/L (OR [95% CI] 5.0 [1.1; 22.9], P=0.038) were independently associated with PFO-related stroke. CONCLUSION: Patients in whom cryptogenic stroke is attributed to a significant PFO have a specific clinical and biological phenotype. Low levels of galectin-3 and osteoprotegerin may help identify patients with PFO-related strokes.

Tenecteplase in acute ischemic stroke: Review of the literature and expert consensus from the French Neurovascular Society.

BACKGROUND: Intravenous alteplase is the only thrombolytic treatment approved for patients with acute ischemic stroke (AIS). Although no randomized controlled trial (RCT) has shown the superiority of tenecteplase over alteplase in AIS, tenecteplase is increasingly used off-label in Stroke Units. The purpose of the present work was to provide an up-to-date set of expert consensus statements on the use of tenecteplase in AIS. METHODS: Members of the working group were selected by the French Neurovascular Society. RCTs comparing tenecteplase and alteplase in the treatment of AIS were reviewed. Recent meta-analysis and real-life experience data on tenecteplase published until 30th October 2021 were also analyzed. After a description of the available data, we tried to answer the subsequent questions about the use of tenecteplase in AIS: What dosage of tenecteplase should be preferred? How effective is tenecteplase for cerebral artery recanalization? What is the clinical effectiveness of tenecteplase? What is the therapeutic safety of tenecteplase? What are the benefits associated with tenecteplase ease of use? Then expert consensus statements for tenecteplase use were submitted. In October 2021 the working group was asked to review and revise the manuscript. In November 2021, the current version of the manuscript was approved. EXPERT CONSENSUS: A set of three expert consensus statements for the use of tenecteplase within 4.5hours of symptom onset in AIS patients were issued: (1) It is reasonable to use tenecteplase 0.25mg/kg when mechanical thrombectomy (MT) is planned. (2) Tenecteplase 0.25mg/kg can be used as an alternative to alteplase 0.9mg/kg in patients with medium- or small-vessel occlusion not retrievable with MT. (3) Tenecteplase 0.25mg/kg could be considered as an alternative to alteplase 0.9mg/kg in patients without vessel occlusion. CONCLUSIONS: These expert consensus statements could provide a framework to guide the clinical decision-making process for the use of tenecteplase according to admission characteristics of AIS patients. However, existing data are limited, requiring inclusions in ongoing RCTs or real-life registries.

[Idiopathic intracranial hypertension: From physiopathological mechanisms to therapeutic decision]. / Hypertension intracrânienne idiopathique : des mécanismes physiopathologiques à la décision thérapeutique.

Clinical features include visual disturbances, headaches, and pulsatile tinnitus that can be associated with reduced quality of life, and a risk of irreversible visual impairment in some cases. Obese women of childbearing age represent the main at-risk population, and the incidence of the disease is increasing because of rising prevalence of obesity worldwide. In addition, an imbalance in sex hormones is reported as a contributing risk factor. The pathophysiology of idiopathic intracranial hypertension involves a disturbance of the evacuation pathway of intracranial fluids caused by the increase in intracranial venous pressure. Brain imaging is useful for diagnosis with several signs including bilateral stenosis of the transverse sinuses that plays a major role in the pathogenesis of the disease by creating a positive feedback loop that increases intracranial venous hypertension and contributes to clinical manifestations. Treatment aims to relieve symptoms and prevent permanent visual impairment. Drug therapies including acetazolamide and topiramate have moderate effectiveness. Among invasive treatments, transverse sinus stenting seems to be the most interesting option to consider in drug-resistant patients. Weight loss remains essential to achieve a sustainable improvement by reducing central venous pressure. Future randomized trials are expected to reach a consensus on this treatment.

[Acute management of spontaneous intracerebral hemorrhage]. / Prise en charge aiguë des hémorragies intracérébrales spontanées.

Intracerebral hemorrhage accounts for approximately 15% of the 115,000 strokes occurring each year in France. Although therapeutic strategies are more limited than for ischemic stroke, major points in the management of intracerebral hemorrhage can reduce short term morbidity and mortality by limiting the expansion of the hematoma and the occurrence of early complications, and long term patients' outcome by reducing the risk of recurrence. This article aims to update the key elements that contribute to improve of the prognosis of intracerebral hemorrhage patients.

[Management of ischemic stroke in the acute phase]. / Prise en charge de l'infarctus cérébral à la phase initiale.

Ischemic stroke accounts for 80% of overall stroke, and is one of the leading causes of death, disability and dementia in worldwide. Management of patients with acute ischemic stroke dramatically improved over time with the implementation of intensive care stroke units, the development of acute recanalization strategies, the optimization of the management of post-stroke complications, and the prevention of early stroke recurrence. The objective of this article is to provide a general overview of the current management of patients with acute ischemic stroke aiming at improving post-stroke outcome.

Stroke in women: When gender matters.

Stroke in women may be considered as a distinct entity due to numerous differences compared with men, including specific epidemiological, etiological, and outcome features along with unique pathophysiological mechanisms. Stroke is the second cause of death in women worldwide with sex-specific causes of stroke in youger women such as pregnancy, post-partum period, oral contraception and migraine. Substitutive hormone treatment in older women is no more recommended in regard of the increased thromboembolic risk it generates. Venous thrombolysis with rtPA and mechanical thrombectomy are now proven to be as efficacious in women as in men. After a stroke, women present poorer quality of life than men attributable to age, more severe stroke, pre-stroke dependency and depression. Recent data concerning the latest epidemiological surveys reveal a shift in trends with the rise of incidence of strokes in young women (≤55 years and 64 years) contrasting with the stability of incidence rates in older women. As science is unvealing sex-related differences in cardiovascular disorders, health policies need to be adapted accordingly to improve stroke prevention and pre-stroke health in women. In the meantime, therapeutical trials should include more women in order to be able to formulate adequate management.

Availability of secondary prevention services after stroke in Europe: An ESO/SAFE survey of national scientific societies and stroke experts.

BACKGROUND: Recurrent stroke is associated with increased disability and cognitive impairment, but the availability of secondary prevention measures after transient ischaemic attack (TIA) or stroke in Europe is uncertain. This limits prioritisation of investment and development of national stroke strategies. METHODS: National stroke representatives throughout Europe were surveyed. Consensus panels reported national data if available, or else expert opinion, estimating the availability of each intervention by quintiles of patients, dichotomised for analysis at 60%. Countries were classified into tertiles of gross domestic product per capita. RESULTS: Of 50 countries, 46 responded; 14/45 (31%) had national stroke registries and 25/46 (54.3%) had national stroke strategies incorporating secondary prevention. Respondents reported that the majority of TIA patients were assessed by specialist services within 48 hours in 74.4% of countries, but in nine countries more than 20% of patients were seen after more than seven days and usually assessed by non-specialists (7/46 countries). Eighty percent of countries deferred blood pressure assessment to primary care, whilst lifestyle management programmes were commonly available in only 46% of countries. Although basic interventions were widely available, interventions frequently not available to more than 60% of patients included: ambulatory cardiac monitoring (40% countries); prescription (26%) and continuation (46%) of statins; blood pressure control at follow-up (44%); carotid endarterectomy within one month (15%); face-to-face follow-up in hospital (33%); direct oral anticoagulants (21%). Gross domestic product per capita and reimbursement of interventions were the commonest predictors of availability of interventions. CONCLUSIONS: Provision of secondary prevention varied, with gaps in care prevalent throughout Europe, particularly in lower income countries.

Air pollution and stroke. A new modifiable risk factor is in the air.

Evidence from epidemiological studies has demonstrated that outdoor air pollution is now a well-known major problem of public health, mainly in low and middle income countries. Contrasting with myocardial infarction, there are few data on the association of air pollution and stroke. METHODS: We propose a narrative literature review of the effects and the underlying biological mechanisms of short- and long-term exposure to air pollutants on stroke risk and mortality, using the following key-words: stroke, cerebrovascular events, ischemic and haemorrhage stroke, transient ischaemic attack, mortality, air pollution and air pollutants. RESULTS: Twenty-one papers were selected. Air pollution, of which whose small particulate matter are the most toxic, contributes to about one-third of the global burden of stroke. We can identify vulnerable patients with classical neuro-vascular risk factors or a prior history of stroke or transient ischemic attack or persons living in low-income countries. Biological mechanisms of this new morbid association are discussed. CONCLUSION: Air pollution should be recognized as a silent killer inducing stroke whose mortality rates remain elevated by its role as a new modifiable neurovascular risk factor, needing public health policies.

A review of psychosocial factors and stroke: A new public health problem.

The role of psychosocial factors (PSF) in increased risk of stroke is a novel public health challenge, but unclear definitions for PSF and the multiple stroke subtypes have led to inconsistent reports. A review of this issue is therefore warranted. METHODS: Several databases were used for this narrative systematic review (Medline, Embase and Cochrane Library). Two independent reviewers evaluated articles from between 2001 and 2018 on the themes of PSF and stroke/transient ischemic attack (TIA). PSF criteria were job strain, psychological interpersonal and behavioral stress, and social deprivation. Ischemic and hemorrhagic stroke and TIA subtypes were also identified. RESULTS: Forty-five cohorts, five case-control studies and two meta-analyses were included. Despite mixed results, PSF were associated with an increased risk of ischemic and hemorrhagic stroke in populations of all ages, and more predominantly in women. CONCLUSION: This broad review shows that the presence of PSF is associated with an increased risk stroke and TIA. As such, PSF must figure in both public health policy and stroke prevention programs, similar to other established metabolic and environmental factors.

Clinical features of pain in amyotrophic lateral sclerosis: A clinical challenge.

Pain in amyotrophic lateral sclerosis (ALS) is paradoxical in this disease of the upper and lower motor neurons. As such, it remains an underestimated and neglected clinical problem because it is poorly identified by physicians, its mechanisms are numerous and its treatments are generally not effective. Pain may be primary in the form of cramps, spasticity and neuropathy, or secondary as nociceptive pain, and may arise before the first motor symptoms. It may also lead to depression and, in all cases, affect patients' daily activities and quality of life. Given the high frequency of pain in ALS, the use of analgesic or sedative drugs is necessary and should reduce the course of the disease. Nevertheless, it is important to understand the pathophysiological mechanisms of pain in ALS, and to train physicians how to detect ALS pain early on and provide dedicated treatments. In France, the implementation of ALS centers is a positive response to the public-health problem resulting from this disorder.

Increased ischemic stroke, acute coronary artery disease and mortality in patients with granulomatosis with polyangiitis and microscopic polyangiitis.

OBJECTIVE: The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates. RESULTS: 125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ±â€¯78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83). CONCLUSION: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.

Adult moyamoya angiopathy in Bourgogne-Franche-Comté: Epidemiology, diagnosis and management.

INTRODUCTION: Moyamoya angiopathy (MMA) is a progressive steno-occlusive disease of the distal internal carotid arteries mainly described in Asia. It induces the development of collateral vascular networks to reduce chronic cerebral hypoperfusion. Symptoms depend on the patient's age in Asia: children are at greater risk of transient or constituted ischemic events, whereas adults are more exposed to hemorrhagic stroke. Data from the literature seem to show that the pattern of MMA in western countries differs from that in Asia. MATERIAL AND METHODS: A retrospective study of patients with MMA was conducted in Bourgogne-Franche-Comté (mid-eastern France). Clinical data (symptoms, risk factors, age at diagnosis, number and timing of recurrences, type of treatment) as well as radiological data (angiographic findings, Suzuki's grade) were analyzed. RESULTS: Seventeen adult patients (9 men, 53%) were followed at the university hospitals of Besançon and Dijon from 2009 to 2016. Fourteen patients (83%) had bilateral disease. The mean age at diagnosis was 49 years (±16), 83% of the patients were Caucasian and 17% originated from Maghreb. Only 17% of the hemispheres had a hemorrhagic form. Ischemic form was more frequent before diagnosis with transient ischemic attack (24% of patients) and stroke (83% of patients). With medical treatment, 9 patients suffered from stroke recurrence (53% of patients) with an average delay of 22.7±34 months. Three patients (18%) had combined surgical management by encephelo-synangiosis and superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis, without symptom recurrence after treatment with an average follow up of 14 months. CONCLUSION: MMA remains a rare cerebrovascular disease in Europe and requires multidisciplinary care. Epidemiological analysis showed differences with the Asian population, especially the predominance of ischemic forms in adults.

Pain after stroke: A review.

Pain after stroke (PAS) is a common clinical problem that is both underdiagnosed and undertreated. Yet, it induces depression and cognitive troubles, and impairs quality of life. To provide tools for practitioners, this report describes the most common PAS syndromes, including central post-stroke pain, spasticity and contractures, shoulder pain and complex regional pain syndromes, as well as headache and chondrocalcinosis, along with their risk factors, their prevention and their specific treatments. In addition, to ensure that the compulsory post-stroke clinical assessment in France is optimal, it is recommended that clinicians be trained in how to diagnose and treat PAS, and even to prevent it by early identification of at-risk patients, with the aim to improve patients' motor and cognitive functions and quality of life.

Associated arterial and venous cerebral manifestations in Behçet's disease.

Behçet's disease is a rare multisystemic vasculitis with an etiology that is still unknown. Neurological manifestations may be seen in approximately 5-15% of patients, and both parenchymal and extraparenchymal neurological involvement has been described. When cerebral venous thrombosis (CVT) is the main extraparenchymal manifestation of Behçet's disease, the condition is then dubbed "angio-Behçet's syndrome". However, arterial involvement is extremely rare, with only one reported case of vasculo-neuro-Behçet's disease, characterized by both venous and intracranial arterial involvement - until now. This report is of two patients diagnosed with Behçet's disease characterized by the concomitant presence of both cerebral arterial manifestations and CVT.

Moya-Moya syndrome after cranial radiation for optic glioma with NF1. Case report and literature review of syndromic cases.

INTRODUCTION: Moya-Moya angiopathy is a neurovascular disease that predisposes to ischemic or hemorrhagic strokes. It is generated by a steno-occlusion of the terminal portion of the internal carotid arteries, which induces the development of abnormal neovessels in the deep regions of the brain. Some pathologies such as sickle cell disease, Down syndrome or Graves' disease may be associated with Moya-Moya angiopathy. These syndromic forms harbor several differences compared with idiopathic Moya-Moya disease. CASE REPORT: We report the case of a young patient who presented with a syndromic form of Moya-Moya angiopathy after cranial radiation therapy for an optic glioma associated with type 1 neurofibromatosis treated by combined revascularization. We discuss the particularities of syndromic forms, in their presentation and management based on a review of the literature. CONCLUSION: Many diseases can be associated with Moya-Moya syndrome. Symptomatic patients should undergo surgery, but the risk of postoperative complications appears to be greater than that encountered in patients with non-syndromic Moya-Moya angiopathy.

[Acute management of ischemic stroke in 2017]. / Prise en charge aiguë des infarctus cérébraux en 2017.

Acute management of ischemic stroke is a burning topic in 2017 since stroke represents the leading cause of acquired handicap in adults. Over the last past years, major improvement took place, especially with the demonstration of the efficacy of mechanical thrombectomy, thus needing to better organize care pathways, and optimize access to neurologists and interventional neuroradiology platforms. Intensive care stroke units remain the pivotal place of patients' management. A multidisciplinary coordination is required, with continuous teaching of all the actors involved in stroke management, so as to increase the number of patients who could benefit from available active treatments.

[Screening and clinical implications of silent atrial fibrillation]. / Dépistage et implications cliniques de la fibrillation atriale silencieuse.

Each year, 5 million new cases of atrial fibrillation (AF) are diagnosed, and the data for the last 20 years show that its incidence has continued to grow. The aging of the population is considered a major explanation for this pandemic phenomenon. The complications associated with atrial arrhythmia are numerous and frequent, with in the first place thromboembolic events. In addition to symptomatic atrial fibrillation, AF may be diagnosed by chance during a systematic ECG, an external Holter or a continuous ECG monitor, or in the memories of implanted cardiac devices. This is called silent AF. Despite numerous studies, silent AF is still largely under-diagnosed and unrecognized in everyday clinical practice, although it is a frequent condition with potentially serious consequences (especially thromboembolic events). Thanks to the development of new diagnostic tools, which are scientifically validated and readily available, the detection of AF has improved significantly, leading to better therapeutic management, in particular anticoagulant therapy. From this perspective, mass screening for silent AF using these new technologies is a major step forward in e-health development. The cost of screening and the heterogeneity of populations affected by silent AF, however, remain major obstacles.