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.

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.

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.

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.

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.

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.

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.

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.

Social deprivation and stroke severity on admission: a French cohort study in Burgundy and the West Indies - Guyana region.

BACKGROUND AND PURPOSE: Although there is growing and convincing evidence that socially deprived patients are at higher risk of stroke and worse outcomes, it remains controversial whether or not they suffer more severe stroke. This study aimed to evaluate the influence of social deprivation on initial clinical severity in patients with stroke. METHODS: A total of 1536 consecutive patients with an acute first-ever stroke (both ischaemic stroke and intracerebral hemorrhage) were prospectively enrolled from six French study centers. Stroke severity on admission was measured by the National Institutes of Health Stroke Scale score. Social deprivation was assessed at the individual level by the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé (EPICES) score, a validated multidimensional questionnaire, and several additional single socioeconomic indicators. Polytomous logistic regression analyses were performed to evaluate the association between social deprivation and stroke severity. RESULTS: In univariate analysis, the EPICES score (P = 0.039) and level of education (P = 0.018) were the only two socioeconomic variables associated with stroke severity. Multivariate analysis of the association between EPICES and National Institutes of Health Stroke Scale scores showed that more deprived patients presented a significantly higher risk of both mild and moderate/severe stroke (odds ratio for mild versus minor stroke, 1.39; 95% confidence interval, 1.06-1.84; odds ratio for moderate/severe versus minor stroke, 1.44; 95% confidence interval, 1.09-1.92). A non-significant trend towards a higher risk of both mild and moderate/severe stroke in less educated patients was observed. CONCLUSIONS: Social deprivation was associated with a more severe clinical presentation in patients with stroke. These findings may contribute to the worse outcome after stroke in deprived patients, and underline the need for strategies to reduce social inequalities for stroke.

Telemedicine for the acute management of stroke in Burgundy, France: an evaluation of effectiveness and safety.

BACKGROUND: In the context of the development of telemedicine in France to address low thrombolysis rates and limited stroke infrastructures, a star-shaped telestroke network was implemented in Burgundy (1.6 million inhabitants). We evaluated the safety and effectiveness of this network for thrombolysis in acute ischemic stroke patients. METHODS: One hundred and thirty-two consecutive patients who received intravenous thrombolysis during a telemedicine procedure (2012-2014) and 222 consecutive patients who were treated at the stroke center of Dijon University Hospital, France (2011-2012) were included. Main outcomes were the modified Rankin scale (mRS) score and case fatality at 3 months. Comparisons between groups were made using multivariable ordinal logistic regression and logistic regression analyses, respectively. RESULTS: Baseline characteristics of telethrombolysis patients were similar to those of patients undergoing thrombolysis locally except for a higher frequency of previous cancer and pre-morbid handicap, and a trend towards greater severity at admission in the former. The distribution of mRS scores at 3 months was similar between groups, as were case-fatality rates (18.9% in the telethrombolysis group versus 16.5%, P = 0.56). In multivariable models, telethrombolysis did not independently influence functional outcomes at 3 months (odds ratio for a shift towards a worse outcome on the mRS, 1.11; 95% confidence interval, 0.74-1.66, P = 0.62) or death (odds ratio, 0.86; 95% confidence interval, 0.44-1.69, P = 0.66). CONCLUSION: The implementation of a regional telemedicine network for the management of acute ischemic stroke appeared to be effective and safe. Thanks to this network, the proportion of patients who benefit from thrombolysis will increase. Further research is needed to evaluate economic benefits.

Impact of thrombolysis in acute ischaemic stroke without occlusion: an observational comparative study.

BACKGROUND AND PURPOSE: The impact of intravenous recombinant tissue plasminogen activator (IV-rtPA) in patients with acute ischaemic stroke (AIS) but no arterial occlusion is currently a matter of debate. This study aimed to assess functional outcome of such patients with respect to IV-rtPA use. METHODS: A retrospective case-control analysis was performed comparing the outcome of AIS patients without arterial occlusion with or without IV-rtPA use. Patients were selected from prospective consecutive observational registries of five European university hospitals. The primary study outcome was excellent outcome at 3 months after stroke, as defined by a modified Rankin Scale (mRS) 0-1. RESULTS: A total of 488 patients without arterial occlusion documented by angiography were included in the present study; 300 received IV-rtPA and 188 did not. No between-group difference was found for excellent outcome before and after adjustment for baseline characteristics (adjusted odds ratio for no IV-rtPA use 0.79, 95% confidence interval 0.51-1.24, P = 0.31). Similar results were found for favourable outcome (defined as a 90-day mRS of 0-2) whereas a higher rate of early neurological improvement was found in IV-rtPA-treated patients (adjusted odds ratio 1.99; 95% confidence interval 1.29-3.07, P = 0.002). Sensitivity analyses yielded similar results. CONCLUSIONS: Our study suggests that AIS patients without visible arterial occlusion treated with IV-rtPA may have no better outcome at 3 months than those untreated. However, only a randomized controlled trial would provide a definitive answer about the impact of rtPA in acute stroke patients without occlusion. Until then, these patients should be treated by rtPA as recommended.

Epidemiology of stroke and transient ischemic attacks: Current knowledge and perspectives.

Because of the growing size and aging of the world's population, the global burden of stroke is increasing dramatically. Current epidemiological data indicate that 16.9 million people suffer a stroke each year, which represents a global incidence of 258/100,000/year, with marked differences between high- and low-income countries, and an age-adjusted incidence 1.5 times higher in men than in women. Although primary prevention has contributed to a decrease in stroke incidence in high-income countries, the so-called 'epidemiological transition' has led to an increase in incidence in middle-to-low-income countries as well. In addition, the incidence of ischemic stroke in young adults is on the rise, suggesting a need for specific preventative interventions in that age group. The number of stroke survivors almost doubled between 1990 and 2010, and has now reached 33 million people. According to epidemiological projections, this number will rise to 77 million by 2030. In France, the number of hospitalizations for an acute cerebrovascular event was about 138,000 in 2009, accounting for 3% of the total national health expenditure. Outcomes after stroke are frequently impaired by complications, including motor handicaps, dementia, depression, fatigue, and a high risk of early rehospitalization and institutionalization, with adverse consequences in terms of socioeconomic costs. In addition, there are 5.9 million stroke-related deaths worldwide every year. Finally, although many analytical epidemiological studies have considerably increased our knowledge of risk factors for stroke, the recent INTERSTROKE study provided evidence that 10 risk factors alone accounted for 88% of all strokes. Many of these risk factors are modifiable, which suggests that efforts should be made to promote interventions that aim to reduce the risk of stroke. A new 'mass approach' aiming to reduce the level of stroke risk factors in all people in a region, regardless of any given individual's level of risk, is currently still being developed. This interesting and innovative way to spread stroke awareness is based on the use of an internationally validated mobile-phone application that can calculate the risk of stroke for any given individual, and also contains a section to educate people on stroke warning symptoms and signs.

[Moyamoya disease: Diagnosis, clinical features, evolution and treatment in 10 patients]. / Maladie de Moyamoya : aspects diagnostiques, cliniques, évolutifs et thérapeutiques chez 10 patients.

INTRODUCTION: Moyamoya disease is a rare chronic cerebrovascular disease. The objective of this article is to report the different clinical and radiological presentations and describe treatments and clinical course of this disease. METHODS: We searched for patients with Moyamoya disease diagnosed at a French university hospital. The diagnosis was based on arteriographic records showing uni- or bilateral stenosis of distal intracranial internal carotid arteries or middle cerebral arteries associated with a classic collateral network imparting a puff of smoke aspect. Data about clinical and radiological symptoms were analyzed for all identified patients. RESULTS: Ten patients were recorded between 2009 and 2014 including one child and nine adults. The initial presentation was intracerebral hemorrhage in two patients, ischemic stroke in six, and either exercice-related transient ischemic attacks or syncope in two. Recurrent events were noted in four patients. Four patients had one or several recurrent vascular events. Eight patients were given medical treatment and none underwent surgery. Secondary Moyamoya syndrome was suspected in two patients, all the others one were considered idiopathic. CONCLUSION: Moyamoya disease is a rare but potentially severe illness. The initial presentation is more frequently an ischemic stroke; recurrences are frequent. The diagnosis is based on arteriography, which is also recommended to search for a cause.

Periodontal disease and stroke: a meta-analysis of cohort studies.

This review aimed to determine the association between periodontal disease and stroke incidence by a meta-analysis of cohort studies. Cohort studies that evaluated the incidence of stroke (fatal or non-fatal, ischaemic or haemorrhagic) and baseline periodontal status and calculated relative risk values were included. The quality of the included studies was assessed using an evaluation grid. The analyses were conducted separately for three outcomes: periodontitis, gingivitis and loss of teeth. Adjusted values of relative risk or of hazard ratio were used to assess risk values in each study. Random effects meta-analyses were conducted when data could be pooled. From the 743 references retrieved, only nine cohort studies were suitable for inclusion in this review. Quality scores of the studies varied greatly. Three prospective studies, which used reliable indicators of periodontal disease, obtained the highest scores. Conversely, three studies that used a subjective evaluation of stroke incidence or diagnosed stroke without imaging obtained the lowest score. The results of the meta-analyses varied depending on the outcome considered and the type of stroke. The risk of stroke was significantly increased by the presence of periodontitis [relative risk 1.63 (1.25, 2.00)]. Tooth loss was also a risk factor for stroke [relative risk 1.39 (1.13, 1.65)]. The risk of stroke did not vary significantly with the presence of gingivitis. This review shows that periodontitis and tooth loss are associated with the occurrence of stroke.

Vascular aphasia outcome after intravenous recombinant tissue plasminogen activator thrombolysis for ischemic stroke.

INTRODUCTION: No data about the specific outcome of aphasia after thrombolysis are available. Our aim was to describe the severity and type of aphasia after stroke thrombolysis. METHODS: This retrospective cohort study included consecutive aphasic patients hospitalized in the Stroke Unit of Dijon (University Hospital, France) between 2004 and 2009 for a first-ever ischemic stroke of the left middle cerebral artery. Aphasic syndromes and their severity (French version of the Boston Diagnostic Aphasia Examination) were evaluated during the first week and 3 months after stroke. RESULTS: In multivariate analyses, the severity of aphasia in the 37 thrombolysed patients was milder than in the 38 nonthrombolysed patients during the first week (adjusted OR = 10.13, 95% CI: 2.43-42.28, p = 0.002) and at 3 months (adjusted OR = 8.44, 95% CI: 2.76-25.80, p = 0.001). The frequency of mild aphasia (conduction or atypical) was not significantly higher in thrombolysed patients during the first week after stroke (adjusted OR = 5.80, 95% CI: 0.82-41.16, p = 0.079). CONCLUSION: The severity of aphasia during the first week and 3 months after stroke is milder in thrombolysed than in nonthrombolysed patients, perhaps because of a greater frequency of conduction and mild atypical aphasia.

Serum 25-hydroxyvitamin D predicts severity and prognosis in stroke patients.

BACKGROUND AND PURPOSE: We aimed to evaluate the association between 25-hydroxyvitamin D (25(OH)D) levels and both clinical severity at admission and outcome at discharge in stroke patients. METHODS: From February 2010 to December 2010, consecutive stroke patients admitted to the Department of Neurology of Dijon, France, were identified. Clinical information was collected. Serum concentration of 25(OH)D was measured at baseline. Stroke severity was assessed at admission using the NIHSS score. Functional impairment was evaluated at discharge using the modified Rankin scale (m-Rankin). Multivariate analyses were performed using logistic regression models. RESULTS: Of the 386 recorded patients, serum 25(OH)D levels were obtained in 382 (median value = 35.1 nM; IQR = 21-57.8). At admission, 208 patients had a NIHSS ≤5, with a higher mean 25(OH)D level than that observed in patients with moderate-to-high severity (45.9 vs. 38.6 nM, P < 0.001). In multivariate analyses, a 25(OH)D level in the lowest tertile (<25.7 nM) was a predictor of a NIHSS ≥6 (OR = 1.67; 95% CI = 1.05-2.68; P = 0.03). The mean 25(OH)D level was lower in patients with moderate-to-severe handicap at discharge (m-Rankin 3-6) than in patients with no or mild handicap (35.0 vs. 47.5 nM, P < 0.001). In multivariate analyses, the lowest tertile of 25(OH)D level (<25.7 nM) was associated with a higher risk of moderate-to-severe handicap (OR = 2.06; 95% CI = 1.06-3.94; P = 0.03). CONCLUSION: A low serum 25(OH)D level is a predictor of both severity at admission and poor early functional outcome in stroke patients. The underlying mechanisms of these associations remain to be investigated.