Restless legs syndrome is a common disease in the general population, affecting women more often than men. It is associated with reduced quality of life in cross-sectional analysis. Parity is a major factor in explaining the sex difference and may guide further clarification of the etiology of the disease.

A sample of 7008 women and men aged 20 to 79 years in a north-east region of Germany, 4900 expected participants. The sample was drawn in two steps: First, 32 communities in the region were selected. Second, within the communities a simple random sample was drawn from residence registries, stratified by gender and age. The data collection and instruments include four parts: oral health examination, medical examination, health-related interview, and a health- and risk-factor-related questionnaire. The oral health examination includes the teeth, periodontium, oral mucosa, craniomandibular system, and prosthodontics. The medical examination includes blood pressure measurements, electrocardiography, echocardiography, carotid, thyroid and liver ultrasounds, neurological screening, blood and urine sampling. The computer-aided health-related interview includes cardiovascular symptoms, utilisation of medical services, health-related behaviours, and socioeconomic variables. The self-administered questionnaire comprises housing conditions, social network, work conditions, subjective well-being and individual consequences from the German reunification.

Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

Background and Purpose-Recent studies have attributed the increased infection vulnerability of patients with stroke to stroke-induced immunosuppression. We have therefore explored the immunological changes in patients with ischemic stroke. Methods-Blood from 46 patients with stroke was analyzed by fluorescent-activated cell sorter to determine leukocyte subsets. To identify changes that represent clinically relevant immunosuppression, we compared patients who developed infection within 14 days after stroke with those who did not. Results-Stroke induced a dramatic and immediate loss of T-lymphocytes, most pronounced within 12 hours after stroke onset. Only patients with subsequent infection exhibited a delay in the recovery of CD4ϩ T-lymphocyte counts. Conclusions-Our data suggest that a loss of CD4ϩ T cell function contributes to the stroke-induced immunosuppression.The CD4ϩ T cell count on the day after stroke may emerge as a predictive marker for poststroke infection allowing, early identification of patients at risk. (Stroke. 2008;39:237-241.)

AIM:Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships. METHODS:The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years. A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound. RESULTS:The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001).This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption. CONCLUSION:There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship. World

I schemic stroke remains a leading cause of death and disability worldwide.1 Planning cost-effective preventive strategies requires precise knowledge of stroke risk factors. 2 Approximately 10% of ischemic strokes occur at ages <45 years, 3 with major long-term socioeconomic con sequences. 4 Stroke prevention results in greater quality-weighted life-yearBackground and Purpose-Although many stroke patients are young or middle-aged, risk factor profiles in these age groups are poorly understood. Methods-The Stroke in Young Fabry Patients (sifap1) study prospectively recruited a large multinational European cohort of patients with cerebrovascular events aged 18 to 55 years to establish their prevalence of Fabry disease. In a secondary analysis of patients with ischemic stroke or transient ischemic attack, we studied age-and sex-specific prevalences of various risk factors. Results-Among 4467 patients (median age, 47 years; interquartile range, 40-51), the most frequent well-documented and modifiable risk factors were smoking (55.5%), physical inactivity (48.2%), arterial hypertension (46.6%), dyslipidemia (34.9%), and obesity (22.3%). Modifiable less well-documented or potentially modifiable risk factors like high-risk alcohol consumption (33.0%) and short sleep duration (20.6%) were more frequent in men, and migraine (26.5%) was more frequent in women. Women were more often physically inactive, most pronouncedly at ages <35 years (18-24: 38.2%; 25-34: 51.7%), and had high proportions of abdominal obesity at age 25 years or older (74%). Physical inactivity, arterial hypertension, dyslipidemia, obesity, and diabetes mellitus increased with age. Conclusions-In this large European cohort of young patients with acute ischemic cerebrovascular events, modifiable risk factors were highly prevalent, particularly in men and older patients. These data emphasize the need for vigorous primary and secondary prevention measures already in young gain in younger patients than in elderly patients, but has received less attention.In the general population and in patient cohorts, risk factor profiles changed with increasing age. 5,6 Most studies of stroke patients aged <50 years were small and methodologically heterogeneous. [7][8][9][10] In the largest single-center study including 1008 ischemic stroke patients aged 15 to 49 years, 7 the most common risk factors were dyslipidemia (60%), smoking (44%), and arterial hypertension (39%), with accumulation in men and increasing age. However, only scarce data exist on the prevalence and risk potential of lifestyle risk factors such as physical inactivity, obesity, 7,8,11 body mass index, waist circumference, 12 and sleep pattern 13,14 in the young. The Stroke in Young Fabry Patients (sifap1) study 15 prospectively recruited a large multinational European cohort of patients aged 18 to 55 years with cerebrovascular event (CVE) to establish their prevalence of Fabry disease. In a secondary analysis of patients with ischemic stroke and transient ischemic attack (TIA), we investigate...

Background and Purpose-Males carry a disproportionate burden of cardiovascular disease. Because males also bear a higher burden of periodontal disease, we investigated the existence of gender differences in the postulated relationship between periodontal infections, tooth loss, and subclinical atherosclerosis. Methods-A total of 1710 randomly enrolled participants between the ages of 45 and 75 with no history of myocardial infarction or stroke received a clinical periodontal examination, carotid scan using high-resolution B-mode ultrasound, and extensive measurements for conventional cardiovascular risk factors (age, education, smoking, alcohol, body mass index, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides) as well as markers of healthy lifestyle and social network. Results-In both genders, measures of current and long-term periodontitis worsened as tooth loss increased. In males but not females, an Ϸ10% difference in carotid artery plaque prevalence was observed between the lowest and highest tertiles of tooth loss (PϽ0.05) and long-term periodontitis (Pϭ0.05) after multivariate adjustment. Similar patterns were observed for intima-media thickness. The influence of gender on carotid artery plaque prevalence was most evident among the younger age group (Ͻ59 years). Between genders, carotid plaque prevalence differed by 10%, 15%, and 25% across increasing levels of tooth loss, and by 5%, 15%, and 25% across increasing levels of long-term periodontitis. Conclusions-Our data suggest that tooth loss and long-term periodontitis are related to subclinical atherosclerosis in men but not women. Gender variations in cardiovascular morbidity or mortality may be explained partly by the differential contributions of novel risk factors across genders.

Old age is associated with a deficient recovery from stroke, but the cellular mechanisms underlying such phenomena are poorly understood. To address this issue, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. Aged rats showed a delayed and suboptimal functional recovery in the post-stroke period. Using BrdU-labeling, quantitative immunohistochemistry and 3-D reconstruction of confocal images, we found that aged rats are predisposed to rapidly develop an infarct within the first few days after ischemia. The emergence of the necrotic zone is associated with a high rate of cellular degeneration, premature accumulation of proliferating BrdU-positive cells that appear to emanate from capillaries in the infarcted area, and a large number of apoptotic cells. With double labeling techniques, we were able to identify, for the first time, over 60% of BrdU-positive cells either as reactive microglia (45%), oligodendrocyte progenitors (17%), astrocytes (23%), CD8+ lymphocytes (4%), or apoptotic cells (<1%). Paradoxically, despite a robust reactive phenotype of microglia and astrocytes in aged rats, at 1-week post-stroke, the number of proliferating microglia and astrocytes was lower in aged rats than in young rats. Our data indicate that aging is associated with rapid infarct development and a poor prognosis for full recovery from stroke that is correlated with premature cellular proliferation and increased cellular degeneration and apoptosis in the infarcted area.