Intracerebral Hemorrhage In Young Adults Research Articles

Global, Regional, and National Burden of Intracerebral Hemorrhage in Young Adults From 1990 to 2021: A Population-Based Study.

Intracerebral hemorrhage (ICH) in young adults demands greater attention, given its poor prognosis; however, there has been a paucity of epidemiological data. The objective of this study is to estimate the temporal trends and distribution characteristics of the disease burden in 204 countries or territories between 1990 and 2021. The data, including incidence, mortality, prevalence, and disability-adjusted life year (DALY) rates were sourced from the Global Burden of Diseases Study 2021. From 1990 to 2021, there was a significant decline in the global incidence (estimated annual percentage change=-1.05), mortality (estimated annual percentage change=-0.92), and DALY (estimated annual percentage change=-1.00) rates of ICH in young adults. In 2021, the highest incidence, mortality, and DALY rates were observed in Southeast Asia, East Asia, and Oceania. Globally, high systolic blood pressure, smoking, and ambient particulate matter pollution were identified as the primary contributors to the largest proportion of DALYs associated with ICH in young adults. The health inequality of ICH in young adults has been reduced over the past 3 decades. There is a considerable degree of heterogeneity in the global burden of ICH in young adults. A decline in the incidence, mortality, prevalence, and DALY rates has been observed from 1990 to 2021, however, the number of absolute cases has increased. These results will enable health care professionals, policymakers, and researchers to refine the implementation of cost-effective policies, the allocation of health care resources, and the management of patients to further mitigate the burden of ICH in young adults.

Etiology, Risk Factors and Outcome of Spontaneous Intracerebral Hemorrhage in Young Adults Admitted to Tertiary Care Hospital in Mogadishu, Somalia.

Spontaneous Intracerebral hemorrhage (ICH) in young patients is less common and not well studied compared to ICH in older patients. The etiology, risk factors and outcome of ICH in young patients may have regional and ethnic differences. The study aims to investigate the clinical characteristics, risk factors, etiology and outcome of spontaneous intracerebral hemorrhage in young adults in Somalia. The study enrolled 168 young patients with ICH (16-50 years) admitted to the neurology department of a tertiary hospital from 2019 to 2022. The information about the demographic details, documented ICH risk factors, etiology and patients' clinical status were retrieved. The etiology of ICH was determined based on clinical, laboratory and radiological findings. Intra-hospital survival status and associated factors were assessed. The mean age of the patients was 35±8.6 years. 99 (59%) of patients were male while 69 (41%) were females. Hypertension 48 (29%) was the most common risk factor, followed by substance abuse. Hypertensive hemorrhage was the most common etiology of ICH 60 (35.7%), followed by cerebral venous thrombosis (CVT) 5(15%), substance abuse 23 (13.7%) and arteriovenous malformation (AVM) in 10 (6%). AVM, CVT, cavernoma, eclampsia, substance abuse and cryptogenic etiology were more common in the 2nd and 3rd decades whereas hypertension was more common in the 4th and 5th decade. Intrahospital mortality was 28% in this study. Factors predicting intrahospital mortality were hematoma volume of greater than 30mL, thrombolytic etiology, brainstem ICH location, substance abuse related etiology, presence of associated mass effect, low GCS score on admission, high systolic blood pressure on admission, and the presence of chronic renal failure. In this study, hypertension, substance abuse, CVT and vascular malformation are the leading causes of ICH in young adults. Intracerebral hemorrhage in the young has different spectrum of etiologies and factors associated with short-term mortality compared to older patients.

Clinical Characteristics, Etiology, Radiological Features, and Outcomes of Intracerebral Hemorrhage in Young Adults at King Abdulaziz Medical City, MNGHA, Riyadh, KSA (P7-5.027)

Clinical Characteristics, Etiology, Radiological Features, and Outcomes of Intracerebral Hemorrhage in Young Adults at King Abdulaziz Medical City, MNGHA, Riyadh, KSA (P7-5.027)

Primary and Secondary Intracerebral Hemorrhage in Pregnant and Nonpregnant Young Adults by SMASH-UP Criteria.

Intracerebral hemorrhage (ICH) is a major cause of maternal morbidity, but its pathophysiology is poorly characterized. We investigated characteristics of pregnancy-associated ICH (P-ICH), compared with ICH in similar aged nonpregnant adults of both sexes. We performed a retrospective analysis of 134 adults aged 18 to 44 years admitted to our center with nontraumatic ICH from January 1, 2012, to December 31, 2021. We compared ICH characteristics among 3 groups: those with P-ICH (pregnant or within 12 months of end of pregnancy); nonpregnant women; and men. We categorized ICH pathogenesis according to a modified scheme, SMASH-UP (structural, medications, amyloid angiopathy, systemic, hypertension, undetermined, posterior reversible encephalopathy syndrome/reversible cerebral vasoconstriction syndrome), and calculated odds ratios and 95% CIs for primary (spontaneous small-vessel) ICH versus secondary ICH (structural lesions or coagulopathy related), using nonpregnant women as the reference. We also compared specific ICH pathogenesis by SMASH-UP criteria and functional outcomes between groups. Of 134 young adults with nontraumatic ICH, 25 (19%) had P-ICH, of which 60% occurred postpartum. Those with P-ICH had higher odds of primary ICH compared with nonpregnant women (adjusted odds ratio, 4.5 [95% CI, 1.4-14.7]). The odds of primary ICH did not differ between men and nonpregnant women. SMASH-UP pathogenesis for ICH differed significantly between groups (P<0.001). While the in-hospital mortality rate was lowest in the P-ICH group (4%) compared with nonpregnant women (13%) and men (24%), 1 in 4 patients with P-ICH were bedbound and dependent at the time of discharge. In our cohort of young adults with ICH, 1 in 5 was pregnancy related. P-ICH differed in pathogenesis compared with non-pregnancy-related ICH in young adults, suggesting unique pathophysiology.

Age-related changes after intracerebral hemorrhage: a comparative proteomics analysis of perihematomal tissue.

The risk factors and causes of intracerebral hemorrhage (ICH) and the degree of functional recovery after ICH are distinct between young and elderly patients. The increasing incidence of ICH in young adults has become a concern; however, research on the molecules and pathways involved ICH in subjects of different ages is lacking. In this study, tandem mass tag (TMT)-based proteomics was utilized to examine the protein expression profiles of perihematomal tissue from young and aged mice 24h after collagenase-induced ICH. Among the 5,129 quantified proteins, ICH induced 108 and 143 differentially expressed proteins (DEPs) in young and aged mice, respectively; specifically, there were 54 common DEPs, 54 unique DEPs in young mice and 89 unique DEPs in aged mice. In contrast, aging altered the expression of 58 proteins in the brain, resulting in 39 upregulated DEPs and 19 downregulated DEPs. Bioinformatics analysis indicated that ICH activated different proteins in complement pathways, coagulation cascades, the acute phase response, and the iron homeostasis signaling pathway in mice of both age groups. Protein-protein interaction (PPI) analysis and ingenuity pathway analysis (IPA) demonstrated that the unique DEPs in the young and aged mice were related to lipid metabolism and carbohydrate metabolism, respectively. Deeper paired-comparison analysis demonstrated that apolipoprotein M exhibited the most significant change in expression as a result of both aging and ICH. These results help illustrate age-related protein expression changes in the acute phase of ICH.

Abstract TP153: Etiology and Radiological Features of Pregnancy-Associated and Non-Pregnancy Associated Intracerebral Hemorrhage in Young Adults

Introduction: Intracerebral hemorrhage (ICH) is a major cause of maternal mortality, but its pathophysiology is not well characterized. We investigated characteristics of pregnancy-associated ICH (PICH), compared with ICH in non-pregnant young adults of both sexes. Methods: We performed a cross-sectional analysis of 134 adults aged 18-44 years admitted with non-traumatic ICH from 1/01/2012 - 12/31/2021. Participants were identified from an internal stroke registry and through the ICHOP (Intracerebral Hemorrhage Outcomes Project) study. We compared ICH etiology between three exposure groups: PICH (ICH occurring in pregnancy or within 3 months postpartum), NPICH in females, and NPICH in males. We categorized ICH etiology as primary (hypertension, amyloid angiopathy, or unknown by SMASH-U criteria) vs secondary (structural, medication, or systemic disease-related). We calculated odds ratios (OR) and 95% confidence intervals (95%CI) for the association of exposure group status with primary vs. secondary ICH, using non-pregnant females as the reference group. Results: Of 134 young adults with non-traumatic ICH, 25 (19%) were pregnant or postpartum. More than half of PICH were in lobar locations (Table) and 40% had unknown etiology (Figure). Adjusting for age, chronic hypertension, and ICH location, pregnant/postpartum patients had highest odds of primary (vs. secondary) ICH (adjusted OR 4.9, 95% CI 1.5-15.9 compared with female NPICH reference group). Conclusion: Almost 1 in 5 young adults with ICH were pregnant or postpartum. PICH differed in location and underlying etiology compared with ICH in non-pregnant young adults, suggesting unique pathophysiology

Abstract TP165: Functional Outcomes at Discharge After Intracerebral Hemorrhage in Young Adults: Comparison by Sex and Pregnancy Status

Introduction: Intracerebral hemorrhage (ICH) is a major cause of maternal morbidity and mortality. While sex differences exist in clinical outcomes of ICH in young adults, it is not known if outcomes differ between pregnancy-associated ICH (PICH) and non-pregnancy-associated ICH (NPICH). Methods: We performed a cross-sectional analysis of 134 adults, aged 18-44 years, admitted to an urban academic medical center with non-traumatic acute ICH between 01/01/2012-12/31/2021. Participants were identified using an internally maintained stroke registry as well as data collected from the ICHOP (Intracerebral Hemorrhage Outcomes Project) study. We compared ICH outcomes between three exposure groups: PICH, NPICH in females, and NPICH in males. PICH was defined as ICH occurring during pregnancy or within 3 months postpartum. The primary outcome was mRS at discharge, with good outcome defined as mRS 0-2 and bad outcome as mRS 3-6. We used logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for the association of exposure group status with bad outcome, with non-pregnant females as the reference group. Results: Characteristics of the study population are detailed in the Table. Individuals with PICH had a lower proportion of chronic hypertension (p&lt;0.0001) and smoking (p=0.02). Adjusting for age, hematoma volume, and ICH location, functional outcomes at discharge did not differ between groups (Figure). Conclusions: Functional outcomes at discharge after ICH were similar in young adults, regardless of sex or pregnancy status, despite a lower prevalence of vascular risk factors in patients with pregnancy-associated ICH.

Intracerebral hemorrhage in young adults: Analysis of etiology, clinical characteristics and discharge outcome

Objective: This study evaluated the etiology, clinical characteristics and discharge outcomes of intracerebral hemorrhage (ICH) without trauma in young adults admitted to a comprehensive stroke center. Subject and method: This was a retrospective study of patients aged under 46 years with nontraumatic ICH admitted from October 2022 to April 2023. Data was collected on demographics, clinical history, hemorrhage location, possible etiology, and discharge outcome. Categorical data was reported as percentage. Chi-squared test was performed to evaluate association of location of ICH, etiology of ICH with the discharge outcome. Result: Forty-five patients met the study criteria, with mean age 35.6 ± 8.1 years including 16 (35.6%) female, 29 (64.4%) male. Headache (86.7%) and hemiparalysis (77.8%) were the most common symptoms. Hematoma was most commonly seen in the deep structures in 21 (46.6%) patients followed by lobar ICH in 17 (37.8%) patients. The most common etiology of ICH was hypertension, which seen in 23 (51.1%) patients, followed by vascular abnormalities in 13 (28.8%) patients. Twenty-two patients (48.9%) had good outcome defined as mRS 0-2. Twenty-three patients (51.1%) had poor outcome with mRS 3-6 at discharge. Location and etiology of hemorrhage were not associated with discharge outcome. Conclusion: Hypertension, a modifiable risk factor, is a major cause of nontraumatic ICH in young adults. In primary care settings, hypertension and life styles were important modifiable risk factors for all subtypes of strokes. Considering that hypertension is an independent risk factor for morbidity and mortality in patients with ICH, this comorbidity should be managed aggressively in young patients as part of a primary prevention strategy related to ICH.

Age-related differences in risk factors, clinical characteristics, and outcomes for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe form of stroke that remains understudied in the young adults. We aimed to investigate the clinical presentation, and risk factors associated with ICH in this age group and compare them to older patients. Our study included ICH patients admitted between March 2016 and December 2021 in the First Affiliated Hospital of Chongqing Medical University from our ongoing prospective cohort database. Demographic characteristics, etiology, risk factors, and clinical outcomes were compared between elderly and young patients. Furthermore, logistic regression analysis was employed to explore risk factors associated with the functional outcome at 3-months. We selected 1,003 patients (mean age, 59.9 ±13.8 years old), 746 (74.4%) patients were aged >50 years. The logistic regression analysis showed young patients have a higher proportion of secondary ICH, higher white blood cell count and higher body mass index (BMI), but less diabetes mellitus. Of all patients, predictors of 3-month functional independence was first-ever ICH and age ≤50 years. The history of nephropathy and stroke, higher baseline NIHSS score, larger hematoma volume, and the presence of hydrocephalus were associated with poor outcomes. And the white blood cell count could significantly influence the prognosis among young ICH patients. Three-month functional outcome based on modified Rankin scale score was better in young patients than the elderly (OR, 1.232; 95% CI, 1.095-1.388; p < 0.001). The highest incidence of ICH occurs in the age groups of 50-59 and 60-69. ICH in young adults had higher white blood cell and BMI compared to the elderly, and differs in etiological distribution. The young patients also had similar short-term mortality but more favorable functional outcomes than the elderly. Furthermore, NIHSS score and larger hematoma volumes were associated with poor outcome in all patients.

GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals.

Arteriovenous malformations (AVMs) are fast-flow vascular malformations and refer to important causes of intracerebral haemorrhage in young adults. Getting deep insight into the genetic pathogenesis of AVMs is necessary. Herein, we identified two vital missense variants of G protein-coupled receptor (GPCR) associated sorting protein 1 (GPRASP1) in AVM patients for the first time and congruously determined to be loss-of-function variants in endothelial cells. GPRASP1 loss-of-function caused endothelial dysfunction in vitro and in vivo. Endothelial Gprasp1 knockout mice suffered a high probability of cerebral haemorrhage, AVMs and exhibited vascular anomalies in multiple organs. GPR4 was identified to be an effective GPCR binding with GPRASP1 to develop endothelial disorders. GPRASP1 deletion activated GPR4/cAMP/MAPK signalling to disturb endothelial functions, thus contributing to vascular anomalies. Mechanistically, GPRASP1 promoted GPR4 degradation. GPRASP1 enabled GPR4 K63-linked ubiquitination, enhancing the binding of GPR4 and RABGEF1 to activate RAB5 for conversions from endocytic vesicles to endosomes, and subsequently increasing the interactions of GPR4 and ESCRT members to package GPR4 into multivesicular bodies or late endosomes for lysosome degradation. Notably, the GPR4 antagonist NE 52-QQ57 and JNK inhibitor SP600125 effectively rescued the vascular phenotype caused by endothelial Gprasp1 deletion. Our findings provided novel insights into the roles of GPRASP1 in AVMs and hinted at new therapeutic strategies.

Amyloid-β (Aβ)-Related Cerebral Amyloid Angiopathy Causing Lobar Hemorrhage Decades After Childhood Neurosurgery.

Recent reports raise the possibility of cerebral amyloid angiopathy (CAA) leading to intracerebral hemorrhage in young adults following childhood neurosurgery, suggesting transmission of amyloid-β (Aβ) through neurosurgical procedures including dura mater grafting. Parenchymal Aβ deposition, and to a lesser extent tau aggregation, similar to that seen in Alzheimer disease, have also been described. We conducted a database review of 634 consecutive intracerebral hemorrhage patients aged <65 years at a tertiary stroke center over 20 years to identify such patients. We identified 3 patients aged in their thirties who presented with spontaneous lobar intracerebral hemorrhage, with imaging or neuropathology consistent with CAA, and a history of childhood neurosurgery. Two of these patients had undergone a dural repair using cadaveric dura mater (Lyodura). In addition to CAA, both patients had neuropathologically confirmed parenchymal Aβ and tau deposits, characteristic of Alzheimer disease. Our findings support the concept of neurosurgical Aβ transmission but suggest that such cases are rare in standard clinical practice.

Prevalence and characterization of cerebral small vessel disease in young adults with intracerebral hemorrhage.

Cerebral small vessel disease (CSVD) is the main cause of intracerebral hemorrhage (ICH) in older individuals but has not been systematically studied in younger people. We aimed to evaluate the prevalence and characteristics of CSVD in young adults with symptomatic ICH. We conducted a cohort study of consecutive adults aged 18-50 years with non-traumatic ICH. All patients were evaluated with brain and vascular imaging. Using validated imaging markers (cerebral microbleeds (CMBs), white matter hyperintensities and/or lacunes), patients were categorized as having CSVD-related ICH or non-CSVD-related ICH. Factors associated with CSVD were evaluated using multivariable analyses. CSVD subtypes were characterized using pre-specified criteria. Of 146 young adults with ICH (mean age = 37.7), CSVD was present in 41 patients (28.1%; 95% confidence interval (CI) = 21.0-36.1). In multivariable analysis, older age, male sex, and hypertension were independently associated with the presence of CSVD. Deep perforator arteriopathy (48.8%) and mixed CSVD (31.7%) were the most common CSVD subtypes. Our results suggest that CSVD is a frequent cause of ICH in young adults and provide new insights into the characterization of the disease. These findings may have important implications since the treatment and management differ from other causes of ICH.

MRI Characterization of Non-traumatic Intracerebral Hemorrhage in Young Adults.

Background and Purpose: Non-traumatic intracerebral hemorrhage (ICH) in younger population is a relatively rare event but is associated with considerable mortality and poor functional outcome. Imaging plays a crucial role in determining the underlying cause and guide treatment of ICH. In up to 41% of patients in prior studies, the underlying cause remained elusive. However, the usage of MRI as part of diagnostic work-up was scanty. We aimed to analyze MRI findings of ICH in younger patients and assess specificity and sensitivity of MRI in detecting structural or local underlying causes of ICH.Methods: We included patients aged 15–49 years with first-ever ICH identified from a prospective hospital discharge registry, 2000–2010. All study patients underwent MRI within 3 months of ICH. Imaging data was analyzed by a senior neuroradiologist blinded to final clinical diagnosis. We calculated the diagnostic accuracy of MRI in detecting structural/local underlying causes.Results: Of our 116 patients (median age, 39; 67% males), structural/local causes were the leading causes of ICH (50.0%), and of these, bleeding cavernomas (23.3%) were the most frequent followed by arteriovenous malformations (12.9%), cerebral venous thrombosis (CVT) (7.8%), brain tumors (5.2%), and moyamoya disease (0.9%). Lobar location of ICH was more prevalent in younger patients. MRI was highly sensitive (90.0%; 95% confidence interval, 79.5–96.2%) for detection of structural/local causes compared with angiographic imaging (55.6%; 95% CI, 40.0–70.4%), while MRI was less specific (87.3%; 95% CI, 75.5–94.7%) for structural/local causes, compared with angiographic imaging (97.4%; 95% CI, 86.5–99.9%).Conclusion: MRI was highly sensitive for the detection of structural and local causes underlying ICH in young adults. Thus, MRI should be considered in the diagnostic work-up of all young ICH patients to enable targeted secondary prevention.

Hypertension is a Leading Cause of Nontraumatic Intracerebral Hemorrhage in Young Adults

Objective: To evaluate the etiology and discharge outcome of nontraumatic intracerebral hemorrhage (ICH) in young adults admitted to a comprehensive stroke center. Methods: A retrospective chart review was performed on patients with a discharge diagnosis of nontraumatic ICH admitted from 7/1/2011 to 6/30/2016. Data was collected on demographics, clinical history, ICH score, hemorrhage location, do-not-resuscitate (DNR) orders, likely etiology, and discharge disposition. Categorical data was reported as percentage. Chi-squared test was performed to evaluate association of location of ICH, etiology of ICH, and ICH score with the discharge outcome. Results: Sixty-three patients met the study criteria, with mean age 35.4 ± 6.4 years including 26 (41%) women and 40 (64%) whites. Headache (65%) and change in mental status (48%) were the most common presenting symptoms. Hemorrhage was most commonly seen in the deep structures in 29 (46%) patients followed by lobar ICH in 14 (22%) patients. The most common etiology of ICH was hypertension in 23 (37%) patients, followed by vascular abnormalities in 18 (29%) patients. Forty-two (67%) had good outcome defined as discharge to home (n = 25) or acute inpatient rehabilitation (n = 17). Twenty-one (33%) patients had bad outcome with discharge to skilled nursing facility (n = 6), hospice (n = 1) or died in the hospital (n = 14). Hospital DNR orders were noted in 11 (18%) patients. Higher ICH score (P < .0001) and use of DNR orders (P < .0001) were associated with bad outcome. All 11 patients with DNR orders died in the hospital. Location or etiology of hemorrhage were not associated with discharge outcome. Conclusions: Hypertension, a modifiable risk factor, is a major cause of nontraumatic ICH in young adults. Aggressive management of hypertension is essential to halt the recent increased trends of ICH due to hypertension. Early DNR orders may need to be cautiously used in the hospital.

Somatic mutations in intracranial arteriovenous malformations.

BackgroundIntracranial arteriovenous malformation (AVM) is a common cause of primary intracerebral hemorrhage in young adults. Lesions typically are sporadic and contain somatic mutations in KRAS or BRAF. The purpose of this study was to identify somatic mutations in a cohort of participants with brain AVM and to determine if any genotype-phenotype associations exist.MethodsHuman brain AVM specimens (n = 16) were collected during a clinically-indicated procedure and subjected to multiplex targeted sequencing using molecular inversion probe (MIP-seq) for mutations in KRAS, BRAF, HRAS, NRAS, and MAP2K1. Endothelial cells (ECs) were separated from non-ECs by immune-affinity purification. Droplet digital PCR (ddPCR) was used to confirm mutations and to screen for mutations that may have been missed by MIP-seq. Patient and AVM characteristics were recorded.ResultsWe detected somatic mutations in 10 of 16 specimens (63%). Eight had KRAS mutations [G12D (n = 5), G12V (n = 3)] and two had BRAF mutations [V600E (n = 1), Q636X (n = 1)]. We found no difference in age, sex, presenting symptom, AVM location, or AVM size between patients with a confirmed mutation and those without. Nor did we observe differences in these features between patients with KRAS or BRAF mutations. However, two patients with BRAF mutations presented at an older age than other study participants.ConclusionsSomatic mutations in KRAS and, less commonly in BRAF, are found in many but not all intracranial AVM samples. Currently, there are no obvious genotype-phenotype correlations that can be used to predict whether a somatic mutation will be detected and, if so, which gene will be mutated.

Interventions for treating brain arteriovenous malformations in adults.

Brain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults. Brain AVMs also cause seizure(s) and focal neurological deficits (in the absence of haemorrhage, migraine or an epileptic seizure); approximately one-fifth are incidental discoveries. Various interventions are used in an attempt to eradicate brain AVMs: neurosurgical excision, stereotactic radiosurgery, endovascular embolization, and staged combinations of these interventions. This is an update of a Cochrane Review first published in 2006, and last updated in 2009. To determine the effectiveness and safety of the different interventions, alone or in combination, for treating brain AVMs in adults compared against either each other, or conservative management, in randomized controlled trials (RCTs). The Cochrane Stroke Group Information Specialist searched the Cochrane Stroke Group Trials Register (last searched 7 January 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1) in the Cochrane Library, MEDLINE Ovid (1980 to 14 January 2019), and Embase OVID (1980 to 14 January 2019). We searched international registers of clinical trials, the contents pages of relevant journals, and bibliographies of relevant articles (November 2009). We also contacted manufacturers of interventional treatments for brain AVMs (March 2005). We sought RCTs of any intervention for brain AVMs (used alone or in combination), compared against each other or against conservative management, with relevant clinical outcome measures. One author screened the results of the updated searches for potentially eligible RCTs for this updated review. Both authors independently read the potentially eligible RCTs in full and confirmed their inclusion according to the inclusion criteria. We resolved disagreement by discussion. We assessed the risk of bias in included studies and applied GRADE. We included one trial with 226 participants: A Randomized trial of Unruptured Brain Arteriovenous Malformations (ARUBA), comparing intervention versus conservative management for unruptured brain AVMs (that had never bled). The quality of evidence was moderate because we found just one trial that was at low risk of bias other than a high risk of performance bias due to participants and treating physicians not being blinded to allocated treatment. Data on functional outcome and death at a follow-up of 12 months were provided for 218 (96%) of the participants in ARUBA. In this randomized controlled trial (RCT), intervention compared to conservative management increased death or dependency (modified Rankin Scale score ≥ 2, risk ratio (RR) 2.53, 95% confidence interval (CI) 1.28 to 4.98; 1 trial, 226 participants; moderate-quality evidence) and the proportion of participants with symptomatic intracranial haemorrhage (RR 6.75, 95% CI 2.07 to 21.96; 1 trial, 226 participants; moderate-quality evidence), but there was no difference in the frequency of epileptic seizures (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 226 participants; moderate-quality evidence). Three RCTs are ongoing. We found moderate-quality evidence from one RCT including adults with unruptured brain AVMs that conservative management was superior to intervention with respect to functional outcome and symptomatic intracranial haemorrhage over one year after randomization. More RCTs will help to confirm or refute these findings.

In-Hospital and Long-Term Prognosis after Spontaneous Intracerebral Hemorrhage among Young Adults Aged 18-65 Years

Background: Spontaneous intracerebral hemorrhage (ICH) accounts for 10%-15% of all strokes and has an estimated annual incidence of 5/100,000 in young adults. Limited data on prognosis after ICH in young adults are available. We aimed to identify prognostic predictors after ICH among adults aged 18-65 years. Methods: We retrospectively selected all patients with ICH from a prospective single-center registry of adults with first stroke before 65 years between 1997 and 2002. We recorded in-hospital mortality as well as mortality and recurrent stroke after discharge until December 1, 2018. For in-hospital analysis, we compared patients that died in-hospital versus patients discharged alive. For long-term analysis, we compared patients that died in follow-up versus patients still alive. Independent prognostic predictors were identified using multivariate analyses. Results: Among 161 patients included, 24 (14.9%) died in-hospital. Among in-hospital survivors, 5-year survival was 92.0%, 10-year survival 78.1%, and 15-year survival 62.0%. After median follow-up of 17 years, 47.4% of patients died, 18 patients had ischemic stroke, and 6 recurrent ICH. Regarding in-hospital prognosis, coma at admission (OR .02 [.00-.11]) was independent predictor for mortality whereas alcoholic habits (OR 12.32 [1.82-83.30]) was independent predictor for survival. An increasing age (OR 1.08 [1.03-1.12]), higher blood glucose levels (OR 1.01 [1.00-1.01]), and hypertension (OR 2.21 [1.22-4.00]) were independent predictors of long-term mortality after ICH. Conclusions: Alcoholic habits may influence in-hospital survival after ICH in young adults. Long-term mortality in young adults seems to be lower than in elderly and was predicted by higher blood glucose levels and hypertension.

Modifiable Factors are a Major Cause of Non-traumatic Intracerebral Hemorrhage in Young Adults (P1.255)

Modifiable Factors are a Major Cause of Non-traumatic Intracerebral Hemorrhage in Young Adults (P1.255)

Nontraumatic intracerebral haemorrhage in young adults.

Nontraumatic intracerebral haemorrhage (ICH) is a common subtype of stroke with a poor prognosis, high mortality and long-term morbidity. The incidence of ICH increases with age. ICH has not been widely investigated in young adults (herein defined as aged ∼18-50 years) despite an annual incidence of ∼5 per 100,000 individuals. Furthermore, ICH characteristics differ between young and elderly patients. Risk factors for ICH are surprisingly common in young adults, in whom ICH is often caused by structural lesions or hypertension, and only rarely by anticoagulation therapy and cerebral amyloid angiopathy (which are common predisposing factors in elderly patients). High short-term mortality (17% at 3 months) and long-term mortality (>25% at 10 years) persist even in contemporary series from high-income countries, and long-term disability is very common. Thus, an aggressive approach to identifying treatable underlying conditions and preventing ICH recurrence is indicated in young patients, although treatment strategies have generally not been investigated specifically in this age group. This narrative Review summarizes existing knowledge on the epidemiology, risk factors, causes, diagnosis, treatment and outcomes of ICH in young adults. We provide comparisons with the population of elderly patients with ICH and discuss challenges for future research.

MicroRNA-137 and microRNA-195* inhibit vasculogenesis in brain arteriovenous malformations.

Brain arteriovenous malformations (AVMs) are the most common cause of nontraumatic intracerebral hemorrhage in young adults. The genesis of brain AVM remains enigmatic. We investigated microRNA (miRNA) expression and its contribution to the pathogenesis of brain AVMs. We used a large-scale miRNA analysis of 16 samples including AVMs, hemangioblastoma, and controls to identify a distinct AVM miRNA signature. AVM smooth muscle cells (AVMSMCs) were isolated and identified by flow cytometry and immunohistochemistry, and candidate miRNAs were then tested in these cells. Migration, tube formation, and CCK-8-induced proliferation assays were used to test the effect of the miRNAs on phenotypic properties of AVMSMCs. A quantitative proteomics approach was used to identify protein expression changes in AVMSMCs treated with miRNA mimics. A distinct AVM miRNA signature comprising a large portion of lowly expressed miRNAs was identified. Among these miRNAs, miR-137 and miR-195* levels were significantly decreased in AVMs and constituent AVMSMCs. Experimentally elevating the level of these microRNAs inhibited AVMSMC migration, tube formation, and survival in vitro and the formation of vascular rings in vivo. Proteomics showed the protein expression signature of AVMSMCs and identified downstream proteins regulated by miR-137 and miR-195* that were key signaling proteins involved in vessel development. Our results indicate that miR-137 and miR-195* act as vasculogenic suppressors in AVMs by altering phenotypic properties of AVMSMCs, and that the absence of miR-137 and miR-195* expression leads to abnormal vasculogenesis. Ann Neurol 2017;82:371-384.