Association of Presence and Pattern of MRI Markers of Cerebral Small Vessel Disease With Recurrent Intracerebral Hemorrhage.

BACKGROUND Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish ICH etiological subtypes (including cryptogenic ICH) relevant for recurrence risk. METHODS We investigated the risk of recurrent ICH in a large cohort of consecutive ICH survivors with available MRI at baseline. Patients with macrovascular, structural or other identified secondary causes (other than SVD) were excluded. Based on MRI findings, ICH etiology was defined as probable cerebral amyloid angiopathy (CAA) according to the Boston 2.0 criteria, arteriolosclerosis (non-lobar ICH and additional markers of arteriolosclerosis, absent lobar hemorrhagic lesions), mixed SVD (mixed deep and lobar hemorrhagic changes) or cryptogenic (no MRI markers of SVD). Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. Data from an independent multi-center cohort (CROMIS-2 ICH) was used to confirm core findings. RESULTS Of 443 patients with ICH (mean age 67±13 years, 41% female), ICH etiology was mixed SVD in 36.7%, arteriolosclerosis in 23.6%, CAA in 23.0%, and cryptogenic in 16.7%. During a median follow-up period of 5.7 years (IQR 2.9-10.0, 2682 patient-years), recurrent ICH were found in 59 individual patients (13.3%). The highest recurrence rate per 100 person-years was detected in patients with CAA (8.5, 95% CI 6.1-11.7), followed by mixed SVD (1.8, 95% CI 1.1-2.9) and arteriolosclerosis (0.6, 95% CI 0.3-1.5). No recurrent ICH occurred in patients with cryptogenic ICH during 510 person-years follow-up (97.5% CI, 0-0.7); this finding was confirmed in an independent cohort (CROMIS-2 ICH, n=216), in which there was also no recurrence in patients with cryptogenic ICH. In patients with CAA, cortical superficial siderosis was the imaging feature strongest related with ICH recurrence (hazard ratio 5.7, 95% CI 2.4-13.6). CONCLUSIONS MRI-based etiological subtypes are helpful in determining the recurrence risk of ICH; while the highest recurrence risk was found in CAA, recurrence risk was low for arteriolosclerosis, and negligible for cryptogenic ICH

Association of Presence and Pattern of MRI Markers of Cerebral Small Vessel Disease With Recurrent Intracerebral Hemorrhage

BACKGROUND: Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish ICH etiological subtypes (including cryptogenic ICH) relevant for recurrence risk. METHODS: We investigated the risk of recurrent ICH in a large cohort of consecutive ICH survivors with available MRI at baseline. Patients with macrovascular, structural or other identified secondary causes (other than SVD) were excluded. Based on MRI findings, ICH etiology was defined as probable cerebral amyloid angiopathy (CAA) according to the Boston 2.0 criteria, arteriolosclerosis (non-lobar ICH and additional markers of arteriolosclerosis, absent lobar hemorrhagic lesions), mixed SVD (mixed deep and lobar hemorrhagic changes) or cryptogenic (no MRI markers of SVD). Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. Data from an independent multi-center cohort (CROMIS-2 ICH) was used to confirm core findings. RESULTS: Of 443 patients with ICH (mean age 67±13 years, 41% female), ICH etiology was mixed SVD in 36.7%, arteriolosclerosis in 23.6%, CAA in 23.0%, and cryptogenic in 16.7%. During a median follow-up period of 5.7 years (IQR 2.9-10.0, 2682 patient-years), recurrent ICH were found in 59 individual patients (13.3%). The highest recurrence rate per 100 person-years was detected in patients with CAA (8.5, 95% CI 6.1-11.7), followed by mixed SVD (1.8, 95% CI 1.1-2.9) and arteriolosclerosis (0.6, 95% CI 0.3-1.5). No recurrent ICH occurred in patients with cryptogenic ICH during 510 person-years follow-up (97.5% CI, 0-0.7); this finding was confirmed in an independent cohort (CROMIS-2 ICH, n=216), in which there was also no recurrence in patients with cryptogenic ICH. In patients with CAA, cortical superficial siderosis was the imaging feature strongest related with ICH recurrence (hazard ratio 5.7, 95% CI 2.4-13.6). CONCLUSIONS: MRI-based etiological subtypes are helpful in determining the recurrence risk of ICH; while the highest recurrence risk was found in CAA, recurrence risk was low for arteriolosclerosis, and negligible for cryptogenic ICH

Burden of intracerebral haemorrhage in Europe: forecasting incidence and mortality between 2019 and 2050

Background: Anticipating the burden of intracerebral haemorrhage is crucial for proactive management and building resilience against future health challenges. Prior forecasts are based on population demography and to a lesser extent epidemiological trends. This study aims to utilise selected modifiable risk factors and socio-demographic indicators to forecast the incidence and mortality of intracerebral haemorrhage in Europe between 2019 and 2050. Methods: Three intracerebral haemorrhage risk factors identified in the Global Burden of Diseases, Injuries, and Risk Factors study (GBD 2019)—high systolic blood pressure, high fasting plasma glucose, and high body mass index—were utilised to predict the risk-attributable fractions between 2019 and 2050. Disease burden not attributable to these risk factors was then forecasted using time series models (autoregressive integrated moving average [ARIMA]), incorporating the Socio-demographic Index (SDI) as an external predictor. The optimal parameters of ARIMA models were selected for each age-sex-country group based on the Akaike Information Criterion (AIC). Different health scenarios were constructed by extending the past 85th and 15th percentiles of annualised rates of change in risk factors and SDI across all location-years, stratified by age and sex groups. A decomposition analysis was performed to assess the relative contributions of population size, age composition, and intracerebral haemorrhage risk on the projected changes. Findings: Compared with observed figures in 2019, our analysis predicts an increase in the burden of intracerebral haemorrhage in Europe in 2050, with a marginal rise of 0.6% (95% uncertainty interval [UI], −7.4% to 9.6%) in incident cases and an 8.9% (−2.8% to 23.6%) increase in mortality, reaching 141.2 (120.6–166.5) thousand and 144.2 (122.9–172.2) thousand respectively. These projections may fluctuate depending on trajectories of the risk factors and SDI; worsened trends could result in increases of 16.7% (8.7%–25.3%) in incidence and 31.2% (17.7%–48%) in mortality, while better trajectories may lead to a 10% (16.4%–2.3%) decrease in intracerebral haemorrhage cases with stabilised mortality. Individuals aged ≥80 years are expected to contribute significantly to the burden, comprising 62.7% of the cases in 2050, up from 40% in 2019, and 72.5% of deaths, up from 50.5%. Country-wide variations were noted in the projected changes, with decreases in the standardised rates across all nations but varying crude rates. The largest relative reductions in counts for both incidence and mortality are expected in Latvia, Bulgaria, and Hungary—ranging from −38.2% to −32.4% and −37.3% to −30.2% respectively. In contrast, the greatest increases for both measures were forecasted in Ireland (45.7% and 74.4%), Luxembourg (45% and 70.7%), and Cyprus (44.5% and 74.2%). The modelled increase in the burden of intracerebral haemorrhage could largely be attributed to population ageing. Interpretation: This study provides a comprehensive forecast of intracerebral haemorrhage in Europe until 2050, presenting different trajectories. The potential increase in the number of people experiencing and dying from intracerebral haemorrhage could have profound implications for both caregiving responsibilities and associated costs. However, forecasts were divergent between different scenarios and among EU countries, signalling the pivotal role of public health initiatives in steering the trajectories. Funding: TheEuropean Union's Horizon 2020 Research and Innovation Programme under grant agreement No.754517. TheNational Institute for Health and Care Research (NIHR) under its Programme Grants forApplied Research (NIHR202339)

Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults-A Worldwide Meta-analysis: The GOAL Initiative

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 health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide. METHODS: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke 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 Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the 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 (odds ratio 2.49; 95% confidence interval 1.42-4.36). DISCUSSION: 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 highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs

Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults: A Worldwide Meta-analysis: The GOAL-Initiative.

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