Intracerebral Hemorrhage Subtypes Research Articles

ASSOCIATION OF THE TYPE OF INTRACEREBRAL HEMORRHAGE WITH SERIOUS COMPLICATIONS AND PREDICTIVE FACTORS FOR HEMORRHAGIC TRANSFORMATION AFTER THROMBOLYTIC TREATMENT IN PATIENTS WITH ACUTE ISCHEMIC STROKE

Background: Accurate classification of postthrombolytic intracerebral hemorrhage (ICH) subtypes is vital for predicting stroke outcomes and managing ICH. Currently, the recommended classification criteria are the European Cooperative Acute Stroke Study III criteria, including two primary categories: hemorrhagic infarction (HI) and parenchymal hematoma (PH). Objectives: The primary objective of this study was to assess the contribution of various ICH subtypes to serious complications, with the secondary aim to identify associated predictors.Methods: The study examined medical records of patients with acute ischemic stroke receiving thrombolysis at Saraburi Hospital from 2014 to 2022. The logit model with the margins command assessed the association of ICH subtypes with serious complications, and multinomial logistic regression identified potential predictors for HI and PH. Results: Among 345 patients, HI-1, HI-2, PH-1 and PH-2 had prevalence rates of 3.2, 7.8, 4.9 and 7.5%, respectively, while 76.5% did not have ICH. PH-2 demonstrated the strongest correlation with inhospital mortality (adjusted risk ratio [RR] 2.83, 95% CI 1.56-5.13), invasive mechanical ventilator requirement (adjusted RR 3.93, 95% CI 2.09-7.39) and hematoma evacuation (adjusted RR 4.58, 95% CI 1.17-17.95) compared with patients of non-ICH. HI demonstrated a significant prolongation of hospitalization. (adjusted RR 3.30, 95% CI 1.53-7.12). Multinomial logistic regression analysis revealed that prior use of antiplatelet drugs, antihypertensive treatment before rt-PA, white blood cell count ≥11,750 cells/mm3 and baseline Alberta stroke program early CT scores ≤7 were independent predictors for PH. The adjusted odds ratios were 3.06 (95% CI, 1.23-7.57), 6.95 (95% CI, 2.62-18.45), 6.01 (95% CI, 2.17-16.65) and 5.01 (95% CI, 2.00-12.60), respectively. Conclusion: The PH-2 subtype was associated with the highest mortality, while our study demonstrated that the HI subtype, previously considered relatively benign with successful early recanalization, showed a significant prolongation of hospitalization compared with that of patients of non-ICH. High-risk patients of ICH require intensive monitoring to reduce complications.

CADMUS: A Novel MRI-Based Classification of Spontaneous Intracerebral Hemorrhage Associated With Cerebral Small Vessel Disease

Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

Inflammatory cytokines and stroke and its subtypes: a genetic correlation and two-sample Mendelian randomization study

IntroductionThe causal relationship between inflammatory factors and stroke subtypes remains unclear. This study aimed to analyze the causal relationship between 41 inflammatory factors and these two factors using Mendelian randomization (MR).MethodsWe performed a two-sample MR analysis to assess the causal effects of 41 inflammatory cytokines on stroke and its subtypes and conducted a genome-wide association study (GWAS) data. The inverse-variance weighted (IVW) method was adopted as the main MR method, and we performed a series of two-sample Mendelian randomizations and related sensitivity analyses.ResultsThe study indicated some suggestive evidences: using the IVW approach, we found that lower possible levels of IL-4 were positively associated with the occurrence of stroke (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88–0.99, p = 0.014), higher interleukin (IL)-1β, IL-12p70 levels may be positively correlated with the occurrence of stroke (OR = 1.09, 95% CI: 1.01–1.18, p = 0.027; OR = 1.08, 95% CI: 1.02–1.15, p = 0.015). For IS, results showed that lower levels of IL-4, tumor necrosis factor-related apoptosis-inducing ligand were positively associated with the occurrence of possible ischemic stroke (IS) (OR = 0.92, 95% CI: 0.87–0.98, p = 0.006; OR = 0.95, 95% CI: 0.91–1.00, p = 0.031), higher levels of IL-1β, IL-12p70 and vascular endothelial growth factor (VEGF) may be positively correlated with the occurrence of IS (OR = 1.09, 95% CI: 1.00–1.19, p = 0.042; OR = 1.07, 95% CI: 1.01–1.15, p = 0.035; OR = 1.06, 95% CI: 1.00–1.12, p = 0.034). Our findings suggest that decreased IL-17 levels could potentially be linked to a higher likelihood of intracerebral hemorrhage (ICH) (OR = 0.51, 95% CI: 0.28–0.93, p = 0.028). For subtypes of stroke, IS and ICH, higher levels of growth regulated oncogene-α, beta nerve growth factor, IL-18, macrophage colony-stimulating factor, and induced protein 10 upregulated the risk factors while lower levels of IL-2ra and IL-17 upregulated the risk factors.ConclusionIn summary, our research validated that inflammatory markers have a pivotal impact on the development of stroke and could potentially offer a fresh approach to treating this condition.

Deep Medullary Vein and MRI Markers Were Related to Cerebral Hemorrhage Subtypes.

To explore the performance of deep medullary vein (DMV) and magnetic resonance imaging (MRI) markers in different intracerebral hemorrhage (ICH) subtypes in patients with cerebral small vessel disease (CSVD). In total, 232 cases of CSVD with ICH were included in this study. The clinical and image data were retrospectively analyzed. Patients were divided into hypertensive arteriopathy (HTNA)-related ICH, cerebral amyloid angiopathy (CAA)-related ICH, and mixed ICH groups. The DMV score was determined in the cerebral hemisphere contralateral to the ICH. The DMV score was different between the HTNA-related and mixed ICH groups (p < 0.01). The MRI markers and CSVD burden score were significant among the ICH groups (p < 0.05). Compared to mixed ICH, HTNA-related ICH diagnosis was associated with higher deep white matter hyperintensity (DWMH) (OR: 0.452, 95% CI: 0.253-0.809, p < 0.05) and high-degree perivascular space (PVS) (OR: 0.633, 95% CI: 0.416-0.963, p < 0.05), and CAA-related ICH diagnosis was associated with increased age (OR: 1.074; 95% CI: 1.028-1.122, p = 0.001). The DMV score correlated with cerebral microbleed (CMB), PVS, DWMH, periventricular white matter hyperintensity (PWMH), and CSVD burden score (p < 0.05) but not with lacuna (p > 0.05). Age was an independent risk factor for the severity of DMV score (OR: 1.052; 95% CI: 0.026-0.076, p < 0.001). DMV scores, CSVD markers, and CSVD burden scores were associated with different subtypes of ICH. In addition, DMV scores were associated with the severity of CSVD and CSVD markers.

Mendelian randomization study and meta-analysis exploring the causality of age at menarche and the risk of intracerebral hemorrhage and ischemic stroke.

The relationship between the age at menarche (AAM) and the risk of intracerebral hemorrhage (ICH) and ischemic stroke (IS) is still up for debate. The purpose of this study was to investigate potential causal connections between them. Genome-wide association analysis (GWAS) of AAM conducted by the MRC-IEU consortium was utilized for association analyses of ICH and IS by two-sample Mendelian randomization (MR) study. AAM data of the within-family GWAS consortium were used as replication phase data to verify the causal relationship between each other. Inverse variance weighting (IVW) method was the primary method used in this MR study. For additional proof, the weighted median estimation, MR-Egger regression, MR-PRESSO test, and MR-Robust Adjusted Profile Score evaluation were performed. The Cochran's Q test and the MR-PRESSO global test were used, respectively, to examine the sensitivity and pleiotropy. Random effects meta-analysis was utilized to analyze the causal data from the two consortiums to further explore the causality between AAM and ICH, IS. We found that the AAM was causally linked with the risk of ICH (OR = 0.48, 95% CI: 0.28-0.80, p = 0.006). On the contrary, the causal effect from AAM to IS (OR = 0.98, 95% CI: 0.91-1.06, p = 0.64) has not been confirmed. For all subtypes of ICH, we found that nonlobar intracerebral hemorrhage (NLICH, OR = 0.41, 95% CI: 0.23-0.75, p = 0.004) but not lobar intracerebral hemorrhage (LICH, OR = 0.65, 95% CI: 0.34-1.24, p = 0.19) was associated with AAM without surprise. Similarly, we used the within-family GWAS consortium data to explore causality and found that AAM may reduce the risk of ICH (OR = 0.78, 95% CI: 0.72-0.86, p = 9.5 × 10-8 ) and NLICH (OR = 0.68, 95% CI: 0.61-0.75, p = 3.4 × 10-13 ) by IVW methods, but is not related to IS (OR = 0.97, 95% CI: 0.93-1.02, p = 0.26). These findings are further supported by the meta-analysis. Both Cochran's Q test and the MR-PRESSO global test failed to detect the presence of sensitivity. AAM and ICH, particularly NLICH, are causally related, but not LICH, IS, or its subtypes in European population.

Abstract Number: LBA25 Validating Artificial Intelligence Model to Optimize Radiologist Detection of Intracerebral Hemorrhage

Introduction Artificial intelligence (AI) has shown to be able to alert the radiologist to the presence of ischemic stroke secondary to large artery occlusion (LVO) as fast as 1–2 minutes from scan completion hence leading to faster diagnosis and treatment. In addition to acute LVO, AI has become increasingly used for various intracranial pathologies. In particular, accurate and timely detection of intracerebral hemorrhage (ICH) is crucial to provide prompt life‐saving interventions. Therefore, we aimed to validate a new AI application called Viz.ai ICH with the intent to improve diagnostic identification of suspected ICH. Methods We performed a retrospective database analysis of 4,203 consecutive non‐contrast brain CT reports between September 2021 to December 2021 within a single institution. The reports were made by experienced neuroradiologists who reviewed each case for the presence of ICH. Medical students reviewed the neuroradiologists’ reports and identified cases with positive findings for ICH. Each positive case was categorized based on subtype, timing, and size/volume via imaging review by a neuroradiologist. The Viz.ai ICH output was reviewed for positive cases by medical students. This AI model was validated by using descriptive analysis and assessing its diagnostic performance with Viz.ai ICH as the index test compared to the neuroradiologists’ interpretation as the gold standard. Results 387 of 4,203 non‐contrast brain CT reports were positive for ICH according to neuroradiologists. The overall sensitivity of Viz.ai ICH was 68%, specificity was 99%, positive predictive value (PPV) was 90%, and negative predictive value (NPV) was 97%. Subgroup analysis was performed based on hemorrhage subtypes of intraparenchymal, subarachnoid, subdural, and intraventricular. Sensitivities were calculated to be 86%, 57%, 56%, and 42% respectively. Further stratification revealed sensitivity improves with higher acuity and volume/size across all ICH subtypes. Meningioma was found to be a common false‐positive finding (3 of 22, 14%). Table 1 provides a summary of the results. Conclusions Our analysis seems to indicate that AI can accurately detect the presence of ICH particularly for large volume/size ICH.

Monogenic Causes in Familial Stroke Across Intracerebral Hemorrhage and Ischemic Stroke Subtypes Identified by Whole-Exome Sequencing

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot screening and/or WES, depending on stroke subtypes and neuroimaging features at a referral center. The clinical significance of each variant was determined according to the American College of Medical Genetics guidelines. Among 161 probands (mean age at onset 53.2 ± 13.7 years; male 63.4%), 33 participants (20.5%) had been identified with 19 pathogenic/likely pathogenic variants (PVs; WES applied 152/161 = 94.4%). Across subtypes, the highest hit rate (HR) was intracerebral hemorrhage (ICH, 7/18 = 38.9%), particularly with the etiological subtype of structural vasculopathy (4/4 = 100%, PVs in ENG, KRIT1, PKD1, RNF213); followed by ischemic small vessel disease (SVD, 15/48 = 31.3%; PVs in NOTCH3, HTRA1, HBB). In contrast, large artery atherosclerosis (LAA, 4/44 = 9.1%) and cardioembolism (0/11 = 0%) had the lowest HR. NOTCH3 was the most common causative gene (16/161 = 9.9%), presenting with multiple subtypes of SVD (n = 13), ICH (n = 2), or LAA (n = 1). Importantly, we disclosed two previously unreported PVs, KRIT1 p.E379* in a familial cerebral cavernous malformation, and F2 p.F382L in a familial cerebral venous sinus thrombosis. The contribution of monogenic etiologies was particularly high in familial ICH and SVD subtypes in our Taiwanese cohort. Utilizing subtype-guided hotspot screening and/or subsequent WES, we unraveled monogenic causes in 20.5% familial stroke probands, including 1.2% novel PVs. Genetic diagnosis may enable early diagnosis, management and lifestyle modification.Graphical Among 161 familial stroke probands, 33 (20.5%) had been identified pathogenic or likely pathogenic monogenic variants related to stroke. The positive hit rate among all subtypes was high in intracerebral hemorrhage (ICH) and ischemic small vessel disease (SVD). Notably, two previously unreported variants, KRIT1 p.E379* in a familial cerebral cavernous malformation and F2 p.F382L in familial cerebral venous sinus thrombosis, were disclosed. CVT cerebral venous thrombosis; HTN Hypertensive subtype; LAA large artery atherosclerosis; SV structural vasculopathy; U Undetermined.

A symmetric prior knowledge based deep learning model for intracerebral hemorrhage lesion segmentation.

Background: Accurate localization and classification of intracerebral hemorrhage (ICH) lesions are of great significance for the treatment and prognosis of patients with ICH. The purpose of this study is to develop a symmetric prior knowledge based deep learning model to segment ICH lesions in computed tomography (CT). Methods: A novel symmetric Transformer network (Sym-TransNet) is designed to segment ICH lesions in CT images. A cohort of 1,157 patients diagnosed with ICH is established to train (n = 857), validate (n = 100), and test (n = 200) the Sym-TransNet. A healthy cohort of 200 subjects is added, establishing a test set with balanced positive and negative cases (n = 400), to further evaluate the accuracy, sensitivity, and specificity of the diagnosis of ICH. The segmentation results are obtained after data pre-processing and Sym-TransNet. The DICE coefficient is used to evaluate the similarity between the segmentation results and the segmentation gold standard. Furthermore, some recent deep learning methods are reproduced to compare with Sym-TransNet, and statistical analysis is performed to prove the statistical significance of the proposed method. Ablation experiments are conducted to prove that each component in Sym-TransNet could effectively improve the DICE coefficient of ICH lesions. Results: For the segmentation of ICH lesions, the DICE coefficient of Sym-TransNet is 0.716 0.031 in the test set which contains 200 CT images of ICH. The DICE coefficients of five subtypes of ICH, including intraparenchymal hemorrhage (IPH), intraventricular hemorrhage (IVH), extradural hemorrhage (EDH), subdural hemorrhage (SDH), and subarachnoid hemorrhage (SAH), are 0.784 0.039, 0.680 0.049, 0.359 0.186, 0.534 0.455, and 0.337 0.044, respectively. Statistical results show that the proposed Sym-TransNet can significantly improve the DICE coefficient of ICH lesions in most cases. In addition, the accuracy, sensitivity, and specificity of Sym-TransNet in the diagnosis of ICH in 400 CT images are 91.25%, 98.50%, and 84.00%, respectively. Conclusion: Compared with recent mainstream deep learning methods, the proposed Sym-TransNet can segment and identify different types of lesions from CT images of ICH patients more effectively. Moreover, the Sym-TransNet can diagnose ICH more stably and efficiently, which has clinical application prospects.

A Causal Classification System for Intracerebral Hemorrhage Subtypes.

Determining the underlying causes of intracerebral hemorrhage (ICH) is of major importance, because risk factors, prognosis, and management differ by ICH subtype. We developed a new causal CLASsification system for ICH Subtypes, termed CLAS-ICH, based on recent advances in neuroimaging. CLAS-ICH defines 5 ICH subtypes: arteriolosclerosis, cerebral amyloid angiopathy, mixed small vessel disease (SVD), other rare forms of SVD (genetic SVD and others), and secondary causes (macrovascular causes, tumor, and other rare causes). Every patient is scored in each category according to the level of diagnostic evidence: (1) well-defined ICH subtype; (2) possible underlying disease; and (0) no evidence of the disease. We evaluated CLAS-ICH in a derivation cohort of 113 patients with ICH from Massachusetts General Hospital, Boston, USA, and in a derivation cohort of 203 patients from Inselspital, Bern, Switzerland. In the derivation cohort, a well-defined ICH subtype could be identified in 74 (65.5%) patients, including 24 (21.2%) with arteriolosclerosis, 23 (20.4%) with cerebral amyloid angiopathy, 18 (15.9%) with mixed SVD, and 9 (8.0%) with a secondary cause. One or more possible causes were identified in 42 (37.2%) patients. Interobserver agreement was excellent for each category (kappa value ranging from 0.86 to 1.00). Despite substantial differences in imaging modalities, we obtained similar results in the validation cohort. CLAS-ICH is a simple and reliable classification system for ICH subtyping, that captures overlap between causes and the level of diagnostic evidence. CLAS-ICH may guide clinicians to identify ICH causes, and improve ICH classification in multicenter studies. ANN NEUROL 2023;93:16-28.

Metformin Alleviates Delayed Hydrocephalus after Intraventricular Hemorrhage by Inhibiting Inflammation and Fibrosis.

Intraventricular hemorrhage (IVH) is a subtype of intracerebral hemorrhage (ICH) with high morbidity and mortality. Posthemorrhagic hydrocephalus (PHH) is a common and major complication that affects prognosis, but the mechanism is still unclear. Inflammation and fibrosis have been well established as the major causes of PHH after IVH. In this study, we aimed to investigate the effects of metformin on IVH in adult male mice and further explored the underlying molecular mechanisms of these effects. In the acute phase, metformin treatment exerted dose-dependent neuroprotective effects by reducing periependymal apoptosis and neuronal degeneration and decreasing brain edema. Moreover, high-dose metformin reduced inflammatory cell infiltration and the release of proinflammatory factors, thus protecting ependymal structure integrity and subependymal neurons. In the chronic phase, metformin administration improved neurocognitive function and reduced delayed hydrocephalus. Additionally, metformin significantly inhibited basal subarachnoid fibrosis and ependymal glial scarring. The ependymal structures partially restored. Mechanically, IVH reduced phospho-AMPK (p-AMPK) and SIRT1 expression and activated the phospho-NF-κB (p-NF-κB) inflammatory signaling pathway. However, metformin treatment increased AMPK/SIRT1 expression and lowered the protein expression of p-NF-κB and its downstream inflammation. Compound C and EX527 administration reversed the anti-inflammatory effect of metformin. In conclusion, metformin attenuated neuroinflammation and subsequent fibrosis after IVH by regulating AMPK /SIRT1/ NF-κB pathways, thereby reducing delayed hydrocephalus. Metformin may be a promising therapeutic agent to prevent delayed hydrocephalus following IVH.

Low hemoglobin is associated with worse outcomes via larger hematoma volume in intracerebral hemorrhage due to systemic disease.

Whether hemoglobin is associated with outcomes of a specific subtype of intracerebral hemorrhage (ICH) is unknown. A total of 4643 patients with ICH from a multicenter cohort were included in the analysis (64.0% male; mean age [SD], 58.3 [15.2] year), of whom 1319 (28.4%) had anemia on admission. The unsupervised consensus cluster method was employed to classify the patients into three clusters. The patients of cluster 3 were characterized by a high frequency of anemia (85.3%) and mainly composed of patients of systemic disease ICH subtype (SD‐ICH; 90.0%) according to the SMASH‐U etiologies. In SD‐ICH, a strong interaction effect was observed between anemia and 3‐month death (adjusted odds ratio [aOR] 4.33, 95% confidence interval [CI] 1.60–11.9, p = 0.004), and the hemoglobin levels were linearly associated with 3‐month death (aOR 0.75, 95% CI 0.60–0.92; p = 0.009), which was partially mediated by larger baseline hematoma volume (p = 0.008). This study demonstrated a strong linear association between low hemoglobin levels and worse outcomes in SD‐ICH, suggesting that hemoglobin‐elevating therapy might be extensively needed in a specific subtype of ICH.

Rare Missense Functional Variants at COL4A1 and COL4A2 in Sporadic Intracerebral Hemorrhage.

ObjectiveTo test the genetic contribution of rare missense variants in COL4A1 and COL4A2 in which common variants are genetically associated with sporadic intracerebral hemorrhage (ICH), we performed rare variant analysis in multiple sequencing data for the risk for sporadic ICH.MethodsWe performed sequencing across 559 Kbp at 13q34 including COL4A1 and COL4A2 among 2,133 individuals (1,055 ICH cases; 1,078 controls) in United States–based and 1,381 individuals (192 ICH cases; 1,189 controls) from Scotland-based cohorts, followed by sequence annotation, functional impact prediction, genetic association testing, and in silico thermodynamic modeling.ResultsWe identified 107 rare nonsynonymous variants in sporadic ICH, of which 2 missense variants, rs138269346 (COL4A1I110T) and rs201716258 (COL4A2H203L), were predicted to be highly functional and occurred in multiple ICH cases but not in controls from the United States–based cohort. The minor allele of rs201716258 was also present in Scottish patients with ICH, and rs138269346 was observed in 2 ICH-free controls with a history of hypertension and myocardial infarction. Rs138269346 was nominally associated with nonlobar ICH risk (p = 0.05), but not with lobar ICH (p = 0.08), while associations between rs201716258 and ICH subtypes were nonsignificant (p > 0.12). Both variants were considered pathogenic based on minor allele frequency (<0.00035 in European populations), predicted functional impact (deleterious or probably damaging), and in silico modeling studies (substantially altered physical length and thermal stability of collagen).ConclusionsWe identified rare missense variants in COL4A1/A2 in association with sporadic ICH. Our annotation and simulation studies suggest that these variants are highly functional and may represent targets for translational follow-up.

The Relationship of the Type of Intracerebral Hemorrhage to Early Disease Evolution and Long-Term Prognosis After r-tPA Thrombolysis.

To investigate the relationship of different subtypes of intracerebral hemorrhage (ICH) to early disease evolution and long-term prognosis in patients with acute cerebral infarction after intravenous recombinant tissue plasminogen activator(r-tPA). Seventy ischemic stroke patients treated with intravenous r-tPA who underwent computed tomography (CT) within 24 hours after thrombolysis were divided into 4 types (hemorrhagic infarction type 1 [HI-1], HI-2, parenchymal hemorrhage type 1 [PH-1], or PH-2 which according to the size of the hematoma and the presence or absence of space-occupying effect). Early evolution of the disease was observed by the change in the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours after thrombolysis. The long-term prognosis was assessed by the modified Rankin Scale (mRS) score at the third month. There were 17 (24.3%) patients with ICH. Compared with patients in the non-ICH group, HI did not affect early neurological function or clinical outcome at the third month. PH-1 did not increase the risk of early neurological deterioration; however, PH-1 has a tendency to increase the risk of death at the third month (50% vs 11.3%, P = 0.090). PH-2 was significantly related to early neurological deterioration (66.7% vs 3.8%, P < 0.001) and mortality at the third month (50.0% vs 11.3%, P = 0.040). Patients with different subtypes of ICH after thrombolysis have different clinical outcomes. PH-2 is significantly associated with early neurological deterioration and increases mortality at the third month.

Blood Pressure and Outcomes in Patients With Different Etiologies of Intracerebral Hemorrhage: A Multicenter Cohort Study.

BackgroundWe aimed to investigate the association between blood pressure (BP) and outcomes in intracerebral hemorrhage (ICH) subtypes with different etiologies.Methods and ResultsA total of 5656 in‐hospital patients with spontaneous ICH were included between January 2012 and December 2016 in a prospective multicenter cohort study. Etiological subtypes of ICH were assigned using SMASH‐U (structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined) classification. Elevated systolic BP was defined as ≥140 mm Hg. Hypertension was defined as elevated BP for >1 month before the onset of ICH. The primary outcomes were measured as 1‐month survival rate and 3‐month mortality. A total of 5380 patients with ICH were analyzed, of whom 4052 (75.3%) had elevated systolic BP on admission and 3015 (56.0%) had hypertension. In multinomial analysis of patients who passed away by 3 months, systolic BP on admission was significantly different in cerebral amyloid angiopathy (P<0.001), structural lesion (P<0.001), and undetermined subtypes (P=0.003), compared with the hypertensive angiopathy subtype. Elevated systolic BP was dose‐responsively associated with higher 3‐month mortality in hypertensive angiopathy (P trend=0.013) and undetermined (P trend=0.005) subtypes. In cerebral amyloid angiopathy, hypertension history had significant inverse association with 3‐month mortality (adjusted odds ratio, 0.37, 95% CI, 0.20–0.65; P<0.001). Similarly, adjusted Cox regression indicated decreased risk of 1‐month survival rate in the presence of hypertension in patients with cerebral amyloid angiopathy (adjusted hazard ratio, 0.47; 95% CI, 0.24–0.92; P=0.027).ConclusionsThis study suggests that the association between BP and ICH outcomes might specifically depend on its subtypes, and cerebral amyloid angiopathy might be pathologically distinctive from the others. Future studies of individualized BP‐lowering strategy are needed to validate our findings.

Identifying the Specific Subtype of Intracerebral Hemorrhage that is Indicated for Minimally Invasive Craniopuncture.

Surgeries for intracerebral hemorrhage (ICH) remain controversial. Our previous study found that postoperative cerebrospinal fluid (CSF) outflow was associated with high hematoma evacuation efficiency in ICH cases with intraventricular involvement (ICHV) treated with minimally invasive craniopuncture (MIC). This study was designed to identify factors that predict postoperative CSF outflow and the specific subtype of ICHV that may benefit from MIC. A total of 189 MIC needles applied to 125 ICHV patients were retrospectively analyzed. Univariate and multivariate analyses were used to identify independent predictive factors of postoperative CSF outflow. A density of the whole hematoma of ≤ 59 HU [odds ratio (OR) = 8.572, 95% confidence interval (CI) 3.235-22.714, P < 0.001, standardization regression coefficients B' = 0.576] and a distance between the needle tip and the ventricular tear (tip-tear distance) of 21.79-34.15mm (OR = 25.566, 95% CI 8.707-75.074, P < 0.001, B' = 0.883) were identified as independent predictive factors of postoperative CSF outflow. The density of the hematoma within 34.15mm of the tear (clot 3.4) showed no statistical difference from that of the whole hematoma (P = 0.571). A density of clot 3.4 ≤ 60 HU was also a predictive factor of postoperative CSF outflow (area under curve: 0.771). ICHV patients who meet the following conditions may benefit from MIC: (1) The MIC needle tip can be placed in the hematoma 21.79-34.15mm from the ventricular tear; (2) the density of the whole hematoma is low (≤ 59 HU); and (3) the density of clot 3.4 is also low (≤ 60 HU). Future perspective studies should be conducted on this specific patient subtype.

Arrival blood pressure in hypertensive and non-hypertensive spontaneous intracerebral hemorrhage

Background and purposeHypertension is a known risk factor for intracerebral hemorrhage (ICH), but it is unclear whether blood pressure (BP) at hospital arrival can be used to distinguish hypertensive ICH from non-hypertensive etiologies. Patients and methodsWe performed a single-center cohort study using data from consecutive ICH patients over 12 months. ICH characteristics including etiology were prospectively adjudicated by two attending neurologists. Using adjusted linear regression models, we compared first recorded systolic BPs (SBP) and mean arterial pressures (MAP) in patients with hypertensive vs. other ICH etiologies. We then used area under the ROC curve (AUC) analysis to determine the accuracy of admission BP in differentiating between hypertensive and non-hypertensive ICH. ResultsOf 311 patients in our cohort (mean age 70.6 ± 15.6, 50% male, 83% white), the most frequent ICH etiologies were hypertension (50%) and cerebral amyloid angiopathy (CAA; 22%). Mean SBP and MAP for patients with hypertensive ICH was 175.1 ± 32.9 mmHg and 120.4 ± 22.9 mmHg, respectively, compared to 156.4 ± 28.0 mmHg and 109.6 ± 20.3 mmHg in non-hypertensive ICH (p < .001). Adjusted models showed that hypertensive ICH patients had higher BPs than those with CAA (mean SBP difference 10.7 mmHg [95% CI 0.8–20.5]; mean MAP difference 8.1 mmHg [1.1–15.0]) and especially patients with other non-CAA causes (mean SBP difference 23.9 mmHg [15.3–32.4]; mean MAP difference 14.5 mmHg [8.5–20.6]). However, on a patient-level, arrival BP did not reliably discriminate between hypertensive and non-hypertensive etiologies (AUC 0.660 [0.599–0.720]). ConclusionsArrival BP differs between hypertensive and non-hypertensive ICH but should not be used as a primary determinant of etiology, as hypertension may be implicated in various subtypes of ICH.

Abstract TP339: Elevated Admission Troponin Predicts Unfavorable Outcomes After Intracerebral Hemorrhage in Patients With Atrial Fibrillation

Background: Intracerebral hemorrhage (ICH) often carries cardiac implications, and serum troponin has been suggested as a predictive biomarker for patients with ICH and other stroke subtypes. We aimed to determine whether previously described associations between troponin and worse outcomes in ICH patients varied based on the presence of atrial fibrillation (AF). Methods: We performed a single-center cohort study using data from consecutive ICH patients admitted over 12 months. ICH characteristics and 3-month outcomes were prospectively collected, while admission troponin levels were retrospectively abstracted. We performed ordinal and binary logistic regression to determine associations between elevated troponins (&gt;0.05 ng/mL) and 3-month outcomes (using the modified Rankin Scale [mRS]), with multivariable models adjusted for relevant demographics, ICH severity, and comorbidities including AF, anticoagulation use, coronary artery disease (CAD), and chronic kidney disease (CKD). An interaction variable combining elevated troponin and AF was also included in our models. Results: Of 261 ICH patients with troponin measured on admission, 17% (n=44) had elevated troponins. Patients with elevated troponins were not significantly older than patients with normal troponin levels (mean age 74.8±13.6 vs. 70.4±15.4, p=0.08), but were more likely to have AF (36% vs. 21%, p=0.03), CAD (32% vs. 15%, p=0.007), and CKD (16% vs. 5%, p=0.006); ICH size, location, and other predictors were not significantly different between groups. In adjusted models, neither elevated troponin nor AF were independently associated with worse outcomes. However, the interaction between the two was significant (p=0.003), and the presence of elevated admission troponin in the context of AF was significantly associated with worse outcomes (ordinal: common OR 9.8 [95% CI 2.0-47.8]; binary (mRS 4-6): OR 14.4 [95% CI 1.9-106.4]). Conclusions: Troponin may be a useful predictive biomarker in ICH patients with underlying AF, potentially signaling higher levels of cardiac and systemic stress in patients with lower cardiac reserve.

Abstract WP458: Blood Pressure at Hospital Arrival Does Not Reliably Distinguish Hypertensive Intracerebral Hemorrhage

Introduction: Hypertension is a known risk factor for intracerebral hemorrhage (ICH), but it is unclear whether blood pressure (BP) elevation at hospital arrival can reliably distinguish ICH caused by hypertensive angiopathy from other potential etiologies. Methods: We performed a retrospective single-center cohort study using data from consecutive patients admitted with ICH from February-June 2018. Presumed ICH etiology, location, and other clinical predictors were prospectively adjudicated by two attending neurologists. We compared patients’ first recorded systolic BP (SBP) and mean arterial pressure (MAP) at hospital arrival stratified by hypertensive vs. non-hypertensive primary ICH etiology, with further adjustment for demographics and initial arrival location (direct arrival vs. transfer) using linear regression models. In a sensitivity analysis, we used ICH location (deep, lobar, or infratentorial) rather than etiology in our models to account for potential subjectivity in adjudication. Results: There were 110 ICH patients in our cohort (mean age 69.1 [SD 17.7], 55% male, median ICH score 1.5 [IQR 1-2]). The most frequent ICH etiologies were hypertension (58%), cerebral amyloid angiopathy (19%), vascular lesions (6%), and malignancy (5%); 43% of hemorrhages occurred in deep subcortical locations, 37% were lobar, and 14% were infratentorial. Mean SBP and MAP for patients with hypertensive ICH was 158.8 (SD 29.7) and 109.0 (SD 18.3), respectively, compared to 157.1 (SD 33.4) and 108.2 (SD 21.2) in patients with ICH caused by other etiologies (p=0.78; p=0.82). Fully-adjusted regression models showed that, relative to hypertensive ICH, those caused by non-hypertensive etiologies had similar arrival BP (mean SBP and MAP difference [95% CI], -0.2 [-12.3-11.8] and -0.8 [-8.4-6.8], respectively). In a sensitivity analysis, we found that lobar and infratentorial ICH had similar arrival BP relative to deep ICH (mean SBP and MAP difference [95% CI] 2.1 [-11.1-15.3] and 0.2 [-8.3-8.6] for lobar ICH; 6.5 [-12.0-25.0] and 3.8 [-8.0-15.6] for infratentorial ICH). Conclusion: BP at hospital arrival should not be used as a primary determinant of likely ICH etiology, as hypertension may be implicated in various subtypes of ICH.

Abstract WP556: Predicting Modified Rankin Scale Using Prior Cognition Measure: Results From CLEAR III Study

Introduction: Intraventricular hemorrhage (IVH) is a subtype of intracerebral hemorrhage (ICH) accounting for 50% mortality and serious survivor disability. We examined whether screening Mini-Mental State Examination (MMSE) scores assessed at days 30 and/or 180 could predict good functional outcome, measured by modified Rankin Scale (mRS) at days 180 and 365 post-stroke. Methodology: CLEAR III was a multicenter, randomized, phase III trial that tested the benefits of accelerated IVH clot removal. Patients were followed for one year with MMSE and mRS collected at days 30 (D30), 180 (D180) and 365 (D365). Good functional outcome was defined as mRS 0-3. Of 500 patients randomized, 354 known survivors were analyzed. Multivariate logistic regression (MLR) was used to estimate the relationship between good D180 and D365 mRS and D30 and/or D180 MMSE adjusting for age and any ICH location. Results: The model predicted a 15% increase in the odds of good D180 mRS for each unit increase in D30 MMSE (OR [95% CI] =1.15 [1.11, 1.20], p-value&lt;0.001). Based on this model, a score of MMSE of 14 or higher is associated with good D180 mRS with 77% sensitivity, 75% specificity, and 76% correctly classified cases (AUC=0.84). In MLR model, D30 MMSE (AOR [95% CI]=1.14 [1.10, 1.19], p-value&lt;0.001) and thalamus ICH location (AOR [95% CI]=0.18 [0.09, 0.38], p-value&lt;0.001) were significant predictors of good D180 mRS, with no significant association with age (AOR [95% CI]=0.97 [0.94, 1.00], p-value=0.073). Similarly, we saw a 14% increase (AOR [95% CI]=1.14, [1.09, 1.20], p-value&lt;0.001) in the odds of good D365 mRS for each unit increase in D30 MMSE, and 9% increase (AOR [95% CI]=1.09, [1.03, 1.15], p-value=0.002) in the odds of good D365 mRS for each unit increase in D180 MMSE (p-value &lt;0.001, AUC=0.88). D30 MMSE (AOR [95% CI]=1.12 [1.06, 1.18], p-value&lt;0.001), D180 MMSE (AOR [95% CI]=1.12 [1.05, 1.19], p-value=0.001), age (AOR [95% CI]=0.96 [0.92, 1.00], p-value=0.041), and thalamus ICH location (AOR [95% CI]=0.17 [0.07, 0.44], p-value&lt;0.001) were significantly associated with good D365 mRS. Conclusion: Cognition measurements, such as MMSE, may be helpful in predicting good functional outcomes at D180 and D365 post-stroke.

Diffusion-Weighted Imaging Hyperintensities in Subtypes of Acute Intracerebral Hemorrhage: Meta-Analysis.

Background and Purpose- Diffusion-weighted imaging (DWI) hyperintensities in intracerebral hemorrhage (ICH) are associated with increased risk of recurrent ICH, cognitive impairment, and death, but whether these lesions are specific to a subtype of ICH remains uncertain. We investigated the association between DWI lesions and ICH subtype and explored the risk factors for DWI lesions. Methods- In a systematic review of ICH studies, we identified those reporting prevalence of DWI lesions. Two reviewers independently assessed study eligibility and risk of bias and collected data. We determined the pooled prevalence of DWI lesions within 90 days after ICH onset for cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH using random-effects meta-analysis. We calculated odds ratios to compare prevalence of DWI lesions by ICH subtype and to assess risk factors for DWI lesions. Results- Eleven studies (1910 patients) were included. The pooled prevalence of DWI lesions was 18.9% (95% CI, 11.1-26.7) in cerebral amyloid angiopathy- and 21.0% (95% CI, 15.3-26.6) in hypertensive angiopathy-related ICH. There was no difference in the prevalence of DWI lesions between cerebral amyloid angiopathy- (64/292 [21.9%]) and hypertensive angiopathy-related ICH (79/370 [21.4%]; odds ratio, 1.25; 95% CI, 0.73-2.15) in the 5 studies reporting data on both ICH pathogeneses. In all ICH, presence of DWI lesions was associated with neuroimaging features of microangiopathy (leukoaraiosis extension, previous ICH, and presence, and number of microbleeds) but not with vascular risk factors or the use of antithrombotic therapies. Conclusions- Prevalence of DWI lesions in acute ICH averages 20%, with no difference between cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH. Detection of DWI lesions may add valuable information to assess the progression of the underlying microangiopathy.