Background and Objectives:There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional healthcare services. To study the global distribution of risk factors, causes and 3-month mortality of young ischemic stroke patients, by performing a patient data meta-analysis form different cohorts worldwide.Methods:We did a pooled analysis of individual patient data from cohort studies which included consecutive ischemic stroke patients aged 18-50 years. We studied differences in prevalence of risk factors and causes between different ethnic and racial groups, geographic regions and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression.Results:We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Blacks (hypertension, 52.1%; diabetes, 20.7%) and Asians (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often cause of stroke in high-income countries (HICs; both p<0.001), whereas ‘’other determined stroke’’ and ‘’undetermined stroke’’ were higher in low and middle-income countries (LMICs; both p<0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (OR 2.49; 95% CI 1.42-4.36).Discussion:The ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial, and regional differences in incidence of ischemic stroke. Our results also visualize the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve healthcare facilities in LMICs.

IntroductionWorldwide, 2 million patients aged 18–50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients.Methods and analysisThe Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18–50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Ethics and disseminationEthical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by selective motor neuron death. We developed a rat model of ALS expressing a human cytosolic copper-zinc superoxide dismutase (SOD1) transgene with two ALS-associated mutations: glycine to alanine at position 93 (G93A) and histidine to arginine at position 46 (H46R). Although the mechanism of ALS is still unclear, there are many hypotheses concerning its cause, including loss of neurotrophic support to motor neurons. Recent evidence suggests that insulin-like growth factors (IGFs) act as neurotrophic factors, and promote the survival and differentiation of neuronal cells including motor neurons. Their ability to enhance the outgrowth of spinal motor neurons suggests their potential as a therapeutic agent for the patients with ALS. In this study, we investigated IGF-II receptor immunoreactivity in the anterior horns of the lumbar level of the spinal cord in SOD1 transgenic rats with the H46R mutation of different ages as well as in normal littermates. The double-immunostaining for IGF-II receptor and glial fibrillary acidic protein (GFAP) demonstrated colocalization on reactive astrocytes (**p < 0.001) in the end-stage transgenic rats, whereas it was not evident at the pre-symptomatic stage or at the onset of the disease. Our results demonstrated the IGF-II receptor up-regulation in reactive astrocytes in the spinal cord of transgenic rats, which may reflect a protective response against the loss of IGFrelated trophic factors. We suggest that IGF receptors may play a key role in the pathogenesis, and may have therapeutic implications in ALS.amyotrophic lateral sclerosis; insulin-like growth factor; transgenic rat; IGF receptor; SOD1 Tohoku

Mongolia ranks third in the world in stroke-related deaths. Loss of skeletal muscle mass and function, known as sarcopenia, is associated with a higher risk of various metabolic disorders such as stroke. Thus, screening of sarcopenia is important. Hand-grip strength (HGS) can be used to predict sarcopenia in the short term. In this cross-sectional study, we used data (n=1180, mean age of 39.2 ± 15.2 and 33.2% males) from the Mon-Timeline cohort study, a multidisciplinary, prospective, population-based cohort study in Mongolia. A digital grip strength dynamometer (TKK 5401 GRIP D; Takei, Japan) was used to measure HGS. We performed binary logistic regression analysis between HGS and stroke risk. Suspected sarcopenia was defined when HGS is less than the 25th percentile of HGS. In this study, 3.3% of all participants had a stroke. The incidence of stroke was significantly higher (5.2% and 1.9%) in people with suspected sarcopenia. According to body composition, the incidence of stroke was more frequent in sarcopenic obese people: 1.3%, 2.4%, 2.8% and 6.2% in normal (non-obese and non-sarcopenic), sarcopenic (non-obese), obese (non-sarcopenic) and sarcopenic obese groups, respectively. In regression analysis, the OR (95% CI) was 2.84 (1.44; 5.59) for sarcopenic compared with non-sarcopenic. The adjustments for age, gender, education, body mass index, waist circumference and hypertensive status attenuated the associations, but lower HGS remained significantly associated with a higher risk of stroke. In conclusion, lower HGS was significantly associated with a higher risk of stroke independent of adiposity and hypertensive status in Mongolian adults.