High efficiency and clinical relevance of exome sequencing in the daily practice of neurogenetics.

OBJECTIVE: To assess the efficiency and relevance of clinical exome sequencing (cES) as a first-tier or second-tier test for the diagnosis of progressive neurological disorders in the daily practice of Neurology and Genetic Departments. METHODS: Sixty-seven probands with various progressive neurological disorders (cerebellar ataxias, neuromuscular disorders, spastic paraplegias, movement disorders and individuals with complex phenotypes labelled 'other') were recruited over a 4-year period regardless of their age, gender, familial history and clinical framework. Individuals could have had prior genetic tests as long as it was not cES. cES was performed in a proband-only (60/67) or trio (7/67) strategy depending on available samples and was analysed with an in-house pipeline including software for CNV and mitochondrial-DNA variant detection. RESULTS: In 29/67 individuals, cES identified clearly pathogenic variants leading to a 43% positive yield. When performed as a first-tier test, cES identified pathogenic variants for 53% of individuals (10/19). Difficult cases were solved including double diagnoses within a kindred or identification of a neurodegeneration with brain iron accumulation in a patient with encephalopathy of suspected mitochondrial origin. CONCLUSION: This study shows that cES is a powerful tool for the daily practice of neurogenetics offering an efficient (43%) and appropriate approach for clinically and genetically complex and heterogeneous disorders.

Assessment of Somatosensory Reorganization by Functional Magnetic Resonance Imaging After Hand Replantation.

INTRODUCTION: Amputation of the hand is a rare and extremely intense trauma. Replanting and allografting after this type of injury require a major reorganization of the brain. Brain plasticity, though better known in the context of disorders of the central nervous system, is just as indispensable when the extremities are damaged. MATERIALS AND METHODS: A 17-year-old patient underwent replantation of the nondominant hand after transmetaphyseal amputation after traumatic injury. After 18 days in hospital and subsequent treatment in a physical rehabilitation center, the patient attended clinical and radiology follow-up sessions over the next 2 years. RESULTS: The management of this patient led to an excellent functional outcome in conjunction with successful social and professional reintegration. Electromyography at 18 months confirmed nerve regrowth. Functional magnetic resonance imaging was done at 2 years to evaluate cerebral plasticity. Motor function, largely dependent on the primary motor area, is aided by the addition of secondary and accessory motor areas for both simple and complex movements. A change in sensory information is stimulation in its own right hemisphere and increases solicitation of the contralateral precentral and postcentral gyrus. CONCLUSIONS: There seems to be a real reversible dynamic plasticity under the balance of inhibitory and excitatory influences exerted on the cortical neurons. Any disruption of this balance requires the brain to adapt to the new circumstances to reestablish the hand as a functioning part of the body.

Temporal Trends in Sex Differences With Regard to Stroke Incidence: The Dijon Stroke Registry (1987-2012).

BACKGROUND AND PURPOSE: We evaluated temporal trends in stroke incidence between men and women to determine whether changes in the distribution of vascular risk factors have influenced sex differences in stroke epidemiology. METHODS: Patients with first-ever stroke including ischemic stroke, spontaneous intracerebral hemorrhage, subarachnoid hemorrhage, and undetermined stroke between 1987 and 2012 were identified through the population-based registry of Dijon, France. Incidence rates were calculated for age groups, sex, and stroke subtypes. Sex differences and temporal trends (according to 5-year time periods) were evaluated by calculating incidence rate ratios (IRRs) with Poisson regression. RESULTS: Four thousand six hundred and fourteen patients with a first-ever stroke (53.1% women) were recorded. Incidence was lower in women than in men (112 versus 166 per 100 000/y; IRR, 0.68; P<0.001), especially in age group 45 to 84 years, and for both ischemic stroke and intracerebral hemorrhage. From 1987 to 2012, the lower incidence of overall stroke in women was stable (IRR ranging between 0.63 and 0.72 according to study periods). When considering stroke subtype, a slight increase in the incidence of ischemic stroke was observed in both men (IRR, 1.011; 95% confidence interval, 1.005-1.016; P=0.001) and women (IRR, 1.013; 95% confidence interval, 1.007-1.018; P=0.001). The sex gap in incidence remained unchanged in ischemic stroke and intracerebral hemorrhage. Conversely, the lower subarachnoid hemorrhage incidence in women vanished with time because of an increasing incidence. CONCLUSIONS: The sex gap in stroke incidence did not change with time except for subarachnoid hemorrhage. Despite lower rates, more women than men experience an incident stroke each year because of a longer life expectancy.

Impact of Mechanical Thrombectomy on the Organization of the Management of Acute Ischemic Stroke.

BACKGROUND: Several trials and meta-analyses have recently demonstrated the superiority of endovascular therapy over standard medical treatment in patients presenting with acute ischemic stroke. In order to offer the best possible treatment to a maximum number of patients, many stroke care networks probably have to be reorganized. After analyzing the reliability of data in the literature, an algorithm is suggested for a pre-hospital and in-hospital alert system to improve the timeliness of subsequent treatment: a drip-and-ship approach. SUMMARY: Five recent well-designed randomized studies have demonstrated the benefit of endovascular therapy associated with intravenous fibrinolysis by recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke with confirmation by recent meta-analyses. The keys for success are a very short time to reperfusion, within 6 h, a moderate to severe pre-treatment deficit (National Institute of Health around 17), cerebral imaging able to identify proximal large vessel occlusion in the anterior circulation, a limited infarct core and a reversible penumbra, the use of the most recent devices (stent retriever) and a procedure that avoids general anesthesia, which reduces blood pressure. To meet these goals, every country must build a national stroke infrastructure plan to offer the best possible treatment to all patients eligible for intravenous fibrinolysis and endovascular therapy. The plan may include the following actions: inform the population about the first symptoms of stroke, provide the call number to improve the timeliness of treatment, increase the number of comprehensive stroke centers, link these to secondary and primary stroke centers by telemedicine, teach and train paramedics, emergency doctors and radiologists to identify the stroke infarct, proximal large vessel occlusion and the infarct core quickly, train a new generation of endovascular radiologists to improve access to this therapy. KEY MESSAGE: After 20 years of rt-PA, this new evidence-based therapy is a revolution in stroke medicine that will benefit patients. However, a new robust and multi-disciplinary care strategy is necessary to transfer the scientific data into clinical practice. It will require reorganization of the stroke infrastructure, which will include comprehensive stroke centers and secondary and primary stroke centers. The winners will be patients with severe stroke.

Associations between Thyroid Stimulating Hormone Levels and Both Severity and Early Outcome of Patients with Ischemic Stroke.

We aimed to investigate associations between serum thyroid stimulating hormone (TSH) levels and both severity and outcome after ischemic stroke (IS). A total of 731 patients consecutive IS patients were enrolled (mean age 69.4 ± 15.4, 61.6% men), and serum TSH levels were measured at admission and analyzed according to the tertiles of their distribution (<0.822 vs. 0.822-1.6 vs. >1.6 mUI/l). Associations between TSH and both severity at admission (National Institutes of Health Stroke Scale (NIHSS) scores <5 vs. ≥5) and functional outcome at discharge assessed by the modified Rankin Scale were analyzed using logistic regression and ordinal logistic regression models, respectively. High TSH levels were independently associated with both a decreased risk of NIHSS score ≥5 at admission (prevalence proportion ratio = 0.62; 95% CI 0.41-0.94, p = 0.024 for tertile 3 vs. tertile 1). In addition, patients with high TSH levels had a better functional outcome at discharge (OR 0.43; 95% CI 0.30-0.60, p < 0.001 for tertile 2 vs. tertile 1; OR 0.39; 95% CI 0.27-0.56, p < 0.001 for tertile 3 vs. tertile 1). The mechanisms underlying these associations and their potential exploitation in terms of therapeutic strategies need to be explored.

Association between Admission Serum 25-Hydroxyvitamin D Levels and Functional Outcome of Thrombolyzed Stroke Patients.

BACKGROUND: 25-Hydroxyvitamin D (25(OH)D) deficiency is a frequent condition in patients who suffer a stroke, and several studies suggested that it may be associated with a poorer prognosis. The aim of this study was to investigate specifically the association between 25(OH)D levels and functional outcome at 3 months in ischemic stroke patients treated with intravenous thrombolysis. METHODS: Consecutive ischemic stroke patients who received intravenous thrombolysis were enrolled between 2010 and 2013. Baseline characteristics were collected, and serum concentrations of 25(OH)D were measured within the first 24 hours after admission and were analyzed according to the quartiles of their distribution (<25 nmol/L versus ≥ 25 nmol/L). Multivariable ordinal logistic regression was used to evaluate the association between 25(OH)D and 3-month functional outcome assessed by the modified Rankin score. RESULTS: Three hundred fifty-two patients were included (mean age 68.6 ± 15.8, 50.7% women, mean 25(OH)D level 45 ± 25 nmol/L). The characteristics of the patients only differed with regard to higher premorbid functional impairment in patients with low 25(OH)D. In univariate analysis, the risk of functional impairment in patients with low 25(OH)D levels was greater than that in patients with higher 25(OH)D levels (odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.35-3.27, P = .001). This association was still observed after adjustment for confounding variables (OR 1.70, 95% CI: 1.06-2.71, P = .027). CONCLUSION: A low serum 25(OH)D level is associated with worse functional outcome in patients with acute ischemic stroke treated with intravenous thrombolysis. Further investigations are required to understand the underlying mechanisms of this association.

Hospitalization within the first year after stroke: the Dijon stroke registry.

BACKGROUND AND PURPOSE: This population-based study aimed to identify unplanned hospitalization within the first year after stroke to determine factors associated with it and consequences on survival. METHODS: All first-ever acute strokes occurring in Dijon, France, from 2009 to 2011, were prospectively collected from a population-based registry. Demographics and clinical data, including stroke severity measured by the National Institutes of Health Stroke Scale and disability after stroke, were recorded. For each patient, the first unplanned hospitalization that occurred within 1 year after stroke was retrieved by linking data with the national French Hospital Discharge Database. Predictors of hospitalization and survival at 1 year were identified using logistic regression models. RESULTS: Among the 613 patients recorded, 94 (15.3%) were excluded because of early death. Of the 519 remaining patients, 167 (32.2%) were hospitalized at 1 year. Subsequent hospitalization led to in-hospital death for 16 (9.6%) patients. In multivariable analyses, only a history of hypertension and atrial fibrillation were associated with hospitalization. In stratified analyses, the National Institutes of Health Stroke Scale score was associated with a higher risk of hospitalization (odds ratio, 1.13; 95% confidence interval, 1.03-1.22; P=0.006), whereas only a trend was noted for disability (odds ratio, 2.26; 95% confidence interval, 0.82-6.22; P=0.113) in patients who returned home after the index stroke. Hospitalization was negatively associated with being alive at 1 year (odds ratio, 0.36; 95% confidence interval, 0.19-0.66; P<0.01). CONCLUSIONS: Stroke survivors are at high risk of hospitalization after the episode, and subsequent admission is associated with poor survival, thus highlighting the need for follow-up interventions after discharge to prevent readmission.

Stroke associated with giant cell arteritis: a population-based study.

BACKGROUND: Giant cell arteritis (GCA) is the most common vasculitis in people ≥50 years and can be associated with stroke. We aimed to evaluate the epidemiology and characteristics of stroke in patients with GCA. METHODS: All patients with a biopsy-proven diagnosis of GCA were identified among residents of the city of Dijon, France (152 000 inhabitants), between 2001 and 2012 using a prospective database. Among these, patients who suffered from stroke were retrieved by crossing data from the population-based Dijon Stroke Registry. Demographics and clinical features were recorded. We considered that the stroke was GCA-related if the stroke revealed GCA or occurred between the onset of symptoms and 4 weeks after the start of treatment. RESULTS: Among the 57 biopsy-proven patients with GCA (incidence rate 10.9/100 000/year in individuals ≥50 years), 4 (7.0%) experienced a GCA-related stroke. Three were men and all had ≥2 vascular risk factors and were ≥80 years. The stroke was vertebrobasilar for 3/4 patients and undetermined for the remaining one. The incidence rate of GCA-related stroke in patients ≥50 years was 0.76/100 000/year (95% CI 0 to 2.47), 1.36/100 000/year in men (95% CI 0 to 3.63) and 0.33/100 000/year (95% CI 0 to 1.45) in women. CONCLUSIONS: This population-based study demonstrated that GCA-related stroke essentially affects the vertebrobasilar territory and mainly occurs in old men with associated vascular risk factors. Although rare, GCA symptoms must be searched for in elderly patients with stroke, and optimal vascular prevention must be conducted carefully in patients with GCA with a high vascular risk before initiating GCA treatment.

Takotsubo Cardiomyopathy Following Acute Cerebral Events.

OBJECTIVE: Takotsubo cardiomyopathy (TCM) is characterized by transient apical ventricular dysfunction typically induced by acute stress. Acute cerebral events including ischemic stroke (IS) or epileptic events (EEs) may be associated with massive catecholamine release. We aimed to identify the characteristics and outcomes of patients who experienced the Takotsubo syndrome complicated by IS or EE. METHODS: Between 2008 and 2013, 87 patients were admitted to our intensive care unit for TCM. Of these, 6 had previously experienced acute cerebral symptoms within 2 days of experiencing either IS or EE. Takotsubo syndrome was diagnosed on cardiac MRI, echocardiography, electrocardiography (ECG), biology and coronary angiography data. RESULTS: Five women and 1 man were included in the study. The mean age was 63.7 ± 20.1 years (range 44-84). Four of them (67%) initially presented an acute IS and 2 (33%) had EE. The suspected brain injury was found in the insular cortex for 4 patients and the posterior fossa for 2 patients. Hemiparesis, aphasia and cerebellar symptoms were the main neurological signs. Abnormal ECG findings including ST-segment elevation (33%) or T-wave inversion (50%) developed between a few hours and 48 h after the onset of the IS or EE. Peak troponin was 1.8 (0.79-14.11) µg/l. A transient reduction in the left ventricular ejection fraction (46 ± 12%) with apical hypokinesis was found using echocardiography. Two (33%) patients went on to develop acute heart failure. Coronary angiography confirmed the lack of significant coronary stenosis for all 6 patients. CONCLUSION: TCM can develop within the first few days after an acute cerebral event. It occurs predominantly in women with insular or posterior fossa lesions and is possibly induced by vegetative reactions.

Angelman syndrome: a case series assessing neurological issues in adulthood.

BACKGROUND: This study aimed to evaluate the clinical symptoms of Angelman syndrome (AS) in adults and to identify the neurological pathways affected in this disease. AS is a neurogenetic disorder resulting due to the deletion or inactivation of the ubiquitin-protein-ligase E3A gene on maternal chromosome 15. SUMMARY: A retrospective analysis of data from six adults patients with clinical, electroencephalographic and genetic confirmation of AS was performed. Movement disorders of the hands and mouth, laughing spells, severe expressive speech disorders, a happy nature, hyposomnia and anxiety are the major neurological characteristics of AS in adulthood. Cerebellar ataxia, muscle hypotonia and tremor, though constant in childhood, tend to be attenuated in adulthood. Epilepsy, one of the most frequent symptoms in childhood and in adulthood, is characterised by specific electroencephalographic patterns. Key Messages: These clinical characteristics are important to improve the clinical awareness and genetic diagnosis of AS. Clinicians must be better informed concerning the adult phenotype as it is not well described in the literature. We stress the importance of AS as one of the main causes of intractable epilepsy. The authors suggest frontal and cerebellar dysfunction. Further functional cerebral imaging studies are necessary.

Patient engagement with research: European population register study.

BACKGROUND: Lay involvement in implementation of research evidence into practice may include using research findings to guide individual care, as well as involvement in research processes and policy development. Little is known about the conditions required for such involvement. AIM: To assess stroke survivors' research awareness, use of research evidence in their own care and readiness to be involved in research processes. METHODS: Cross sectional survey of stroke survivors participating in population-based stroke registers in six European centres. RESULTS: The response rate was 74% (481/647). Reasons for participation in register research included responding to clinician request (56%) and to 'give something back' (19%); however, 20% were unaware that they were participating in a stroke register. Research awareness was generally low: 57% did not know the purpose of the register they had been recruited to; 73% reported not having received results from the register they took part in; 60% did not know about any research on stroke care. Few participants (7.6%) used research evidence during their consultations with a doctor. The 34% of participants who were interested in being involved in research were younger, more highly educated and already research aware. CONCLUSIONS: Across Europe, stroke survivors already participating in research appear ill informed about stroke research. Researchers, healthcare professionals and patient associations need to improve how research results are communicated to patient populations and research participants, and to raise awareness of the relationship between research evidence and increased quality of care.

iScore for predicting institutional care after ischemic stroke: a population-based study.

BACKGROUND: We assessed whether the iScore could predict the need for poststroke institutional care. METHODS: Patients with acute ischemic stroke living in Dijon, France, were recorded between 2006 and 2011, using a population-based stroke registry. The iScore was calculated for each patient. A logistic regression model was used to assess the performance of the iScore for predicting the need for placement in a care institution. The discrimination and calibration of the model were assessed using the c statistic and the Hosmer-Lemeshow goodness-of-fit test, respectively. RESULTS: Of the 1199 patients recorded, 124 were excluded because of early death and 95 because of missing for variables included in the iScore. Of the remaining 980 patients, 522 (53.3%) returned home and 458 (46.7%) required placement in a care institution. The median iScore was 123 (interquartile range, 97-148), and the proportion of patients who required placement in a care institution increased with each quintile of risk score. The discrimination of the model was good with a c statistic of .75 (95% confidence interval, .72-.78), as was calibration (P = .35). CONCLUSIONS: The iScore could be useful for predicting the need for placement in a care institution in ischemic stroke patients. Further studies are required to confirm this finding.

Frequency and predictors of stroke after acute myocardial infarction: specific aspects of in-hospital and postdischarge events.

BACKGROUND AND PURPOSE: Stroke is a serious complication after acute myocardial infarction (AMI) and is closely associated with decreased survival. This study aimed to investigate the frequency, characteristics, and factors associated with in-hospital and postdischarge stroke in patients with AMI. METHODS: Eight thousand four hundred eighty-five consecutive patients admitted to a cardiology intensive care unit for AMI, between January 2001 and July 2010. Stroke/transient ischemic attack were collected during 1-year follow-up. RESULTS: One hundred twenty-three in-hospital strokes were recorded: 65 (52.8%) occurred on the first day after admission for AMI, and 108 (87%) within the first 5 days. One hundred six patients (86.2%-incidence rate 1.25%) experienced in-hospital ischemic stroke, and 14 patients (11.4%-incidence rate 0.16%) were diagnosed with an in-hospital hemorrhagic stroke. In-hospital ischemic stroke subtypes according to the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification showed that only 2 types of stroke were identified more frequently. As expected, the leading subtype of in-hospital ischemic stroke was cardioembolic stroke (n=64, 60%), the second was stroke of undetermined pathogenesis (n=38, 36%). After multivariable backward regression analysis, female sex, previous transient ischemic attack (TIA)/stroke, new-onset atrial fibrillation, left ventricular ejection fraction (odds ratio per point of left ventricular ejection fraction), and C-reactive protein were independently associated with in-hospital ischemic stroke. When antiplatelet and anticoagulation therapy within the first 48 hours was introduced into the multivariable model, we found that implementing these treatments (≥1) was an independent protective factor of in-hospital stroke. In-hospital hemorrhagic stroke was dramatically increased (5-fold) when thrombolysis was prescribed as the reperfusion treatment. However, the different parenteral anticoagulants were not predictors of risk in univariable analysis. Finally, only 45 postdischarge strokes were recorded. Postdischarge stroke subtypes showed a more heterogeneous distribution of mechanisms. The annual rate of stroke post-AMI remained stable throughout the 10-year study period. CONCLUSIONS: The present study describes specific predictors of in-hospital and postdischarge stroke in patients with AMI. It showed a marked increase in the risk of death, both during hospitalization and in the year after AMI. After hospital discharge, stroke remains a rare event and is mostly associated with high cardiovascular risk.

Trends in the incidence of ischaemic stroke in young adults between 1985 and 2011: the Dijon Stroke Registry.

BACKGROUND: Recent data have suggested that stroke incidence in young people may be rising. In this population-based study, we aimed to determine whether the incidence of stroke in people aged <55 years old had changed over the last three decades. METHODS: All cases of first-ever stroke (ischaemic stroke, spontaneous intracerebral haemorrhage, and undetermined stroke) occurring in Dijon, France, from 1985 to 2011 were prospectively collected from a population-based registry. Incidence rates were calculated and temporal trends were analysed by age groups and stroke subtypes using a Poisson regression to estimate incidence rate ratios (IRR). Risk factors and premorbid treatments were analysed. RESULTS: Over the 27-year study period, 4506 patients were recorded (53% women, mean age 74.6±14.4, 10.1% aged <55 years). An increase in overall stroke incidence was noted, as was a rise in ischaemic stroke in individuals aged <55 years (IRR 1.308; 95% CI 0.982 to 1.741, p=0.066 for period 1994-2002 vs period 1985-1993, and IRR 1.697; 95% CI 1.340 to 2.150, p<0.001 for period 2003-2011 vs period 1994-2002), which was consistent for men and women. In these young patients, smoking was the most frequent risk factor (43%). CONCLUSIONS: Multiple factors may account for the increased incidence of ischaemic stroke in people aged <55 years including changes in vascular risk factors, better awareness of the disease and treatment options in the population and among practitioners leading to more frequent referrals for specialised care, and improvements in stroke diagnosis. Stroke prevention must be encouraged even in young adults.

Prevalence and prognostic value of headache on early mortality in acute stroke: the Dijon Stroke Registry.

OBJECTIVE: To evaluate the prevalence of headache at onset and its association with 1-month mortality in stroke patients. METHODS: All patients with stroke in Dijon, France (2006-2011), were prospectively identified using a population-based registry. Cox regression models were used to evaluate the association between headache and 30-day all-cause mortality. RESULTS: Among 1411 stroke patients, data about headache were obtained for 1391 (98.6%) of whom 1185 had an ischemic stroke (IS), 201 had an intracerebral hemorrhage (ICH) and five had a stroke of undetermined etiology. Headache was found in 253 (18.2%) patients and was more frequent in those with ICH than in those with IS (46.3% vs 13.5%, p < 0.001). Overall 30-day mortality was 11.7%, and was greater for patients with than those without headache (17.0% vs 10.5%, unadjusted HR 1.70; 95% CI 1.20-2.41, p = 0.003). In multivariable analysis, an association between headache and 30-day mortality was observed (HR 1.51; 95% CI 1.02-2.25, p = 0.042). In stratified analyses, headache was associated with 30-day mortality in ICH (HR 2.09; 95% CI 1.18-3.71, p = 0.011) but not in IS (HR 1.01; 95% CI 0.53-1.92, p = 0.97). CONCLUSION: Headache at stroke onset is associated with a higher risk of early mortality in patients with ICH.

Association between serum concentration of vitamin D and 1-year mortality in stroke patients.

BACKGROUND: The prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency is high in patients presenting with an acute stroke, and it may be associated with greater clinical severity and a poor early functional prognosis. However, no data about its impact on long-term prognosis is available. In this study, we aimed to assess the association between 25(OH)D levels and 1-year mortality in stroke patients. METHODS: From February to December 2010, 382 Caucasian stroke patients admitted to the Department of Neurology of the University Hospital of Dijon, France, were enrolled prospectively. Demographics and clinical information including stroke severity assessed using the National Institutes of Health Stroke Scale score were collected. The serum concentration of 25(OH)D was measured at baseline. Multivariable Cox regression models were used to evaluate the association between 1-year all-cause mortality and serum 25(OH)D levels treated as either a log-transformed continuous variable or dichotomized (<25.7 and ≥25.7 nmol/l) at the first tertile of their distribution. RESULTS: Of the 382 stroke patients included, 63 (16.5%) had died at 1 year. The mean 25(OH)D level was lower in these patients (32.3 ± 22.0 vs. 44.6 ± 28.7 nmol/l, p < 0.001), and survival at 1 year was worse in patients in the lowest tertile of 25(OH)D levels (defined as <25.7 nmol/l); log-transformed 25(OH)D levels were inversely associated with 1-year mortality (hazard ratio, HR = 0.62; 95% confidence interval, 95% CI: 0.44-0.87; p = 0.007), and patients with 25(OH)D levels <25.7 nmol/l were at a higher risk of death at 1 year (HR = 1.95; 95% CI: 1.14-3.32; p = 0.014). In multivariable analyses, the association was no longer significant but a significant interaction was found for age, and stratified analyses by age groups showed an inverse relationship between 25(OH)D levels and 1-year mortality in patients aged <75 years [HR = 0.38; 95% CI: 0.17-0.83; p = 0.015 for log-transformed 25(OH)D levels, and HR = 3.12; 95% CI: 0.98-9.93; p = 0.054 for 25(OH)D levels <25.7 vs. >25.7 nmol/l]. CONCLUSION: A low serum 25(OH)D level at stroke onset may be associated with higher mortality at 1 year in patients <75 years old. Further studies are needed to confirm these findings and to determine whether vitamin D supplementation could improve survival in stroke patients.

Smoking status and severity of ischemic stroke. A population-based study.

We aimed to investigate the impact of smoking status on clinical severity in patients with ischemic stroke event (IS). Patients were prospectively identified among residents of the city of Dijon, France (ca. 151,000 inhabitants), using a population-based registry, between 2006 and 2011. Demographic and clinical data were recorded. The initial clinical severity was quantified by the means of the National Institutes of Health Stroke Scale (NIHSS). Multivariable ordinal logistic regression was used to assess the effect of smoking status on severity. Among the 1,056 recorded patients with IS, data about smoking status were available for 973 (92.1%), of whom 658 (67.3%) were non-smokers, 187 (19.2%) were current smokers, and 128 (13.2%) were former smokers. Compared with non-smoking, former smoking was associated with less severe IS (OR 0.55; 95% CI 0.38-0.82, p = 0.003), whereas this association was not found for current smokers (OR 0.97; 95% CI 0.69-1.36, p = 0.856). Further work is needed to understand the underlying mechanisms of this finding.

Silent atrial fibrillation after ischemic stroke or transient ischemic attack: interest of continuous ECG monitoring.

BACKGROUND: Since atrial fibrillation (AF) may be undiagnosed when asymptomatic and paroxysmal, we aimed to investigate the incidence and determinants of silent AF in patients with acute ischemic stroke or transient ischemic attack (TIA). METHODS: Consecutive patients admitted to the Stroke Unit of the University Hospital of Dijon, France, for acute ischemic stroke or TIA were prospectively enrolled from March to December 2012. Silent AF was assessed by continuous electrocardiography (ECG) monitoring for 24 h after admission. An echocardiography was performed at day 2 ± 1 to measure left ventricular ejection fraction (LVEF) and left auricular (LA) dimensions. RESULTS: Among the 187 patients included, 19 (10%) developed silent AF. Patients with silent AF were markedly older (76 vs. 66 years, p < 0.002), with lower creatinine levels (90 vs. 80 µmol/l, p = 0.030) and were less often smokers (5 vs. 24%, p = 0.058) than patients without silent AF. They also showed a trend towards more frequent hypertension and a recent history of infection. Patients with silent AF had a larger indexed LA volume (37.4 vs. 30.8 ml/m(3), p = 0.057) and LA diameter (23.2 vs. 20.8 mm/m(2), p = 0.059). LVEF in the two groups was similar. In multivariate analysis, only age remained an independent estimate of silent AF. CONCLUSION: Silent AF detected by continuous ECG monitoring is common and closely associated with older age. Further studies are needed to investigate the interest of systematically screening for silent AF for secondary prevention after ischemic stroke/TIA.

Population-based validation of the iScore for predicting mortality and early functional outcome in ischemic stroke patients.

BACKGROUND: We aimed to determine the accuracy of the iScore for predicting mortality and early disability following ischemic stroke in a French population-based study. METHODS: All patients with acute ischemic stroke were identified among residents of the city of Dijon, France, between 2006 and 2011, using a population-based stroke registry. The 30-day iScore and 1-year iScore were calculated. A logistic regression model was used to assess the performance of the iScore for predicting both 30-day and 1-year mortality, and poor functional outcome at discharge (modified Rankin Scale score of 3-6). The discrimination and calibration of the model were assessed using the c-statistic and the Hosmer-Lemeshow goodness-of-fit test, respectively. RESULTS: Among the 1,199 ischemic stroke patients recorded, 107 (8.9%) were excluded because at least one item of data was missing. For the remaining 1,092 patients, the c-statistic was 0.85 (95% CI: 0.82-0.89) for 30-day and 0.84 (0.81-0.87) for 1-year mortality, and calibration was good (p = 0.82 and p = 0.96, respectively, for the Hosmer-Lemeshow test). Similar results were found for disability (c-statistic 0.81, 95% CI: 0.79-0.84, and p = 0.45 for the Hosmer-Lemeshow test). CONCLUSION: This is the first population-based study to demonstrate the accuracy of the iScore for predicting mortality and early disability in ischemic stroke patients.

[Epidemiology and prognosis of stroke in young adults]. / Epidémiologie et pronostic de l'accident vasculaire cérébral du sujet jeune.

Stroke in young adults is not rare since one in ten stroke patients are less than 55 years old, and incidence is 20 to 35/100000 per year at this age. This incidence increased over the last past years because of the rise in the prevalence of diabetes, obesity, and marijuana abuse, and still a high prevalence of smoking. This latter risk factor is the most frequent and accounts for more than one half of young stroke patients. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socioeconomic and quality of life consequences make this disease a main objective for practitioners who should identify individuals at risk and apply preventive strategies.