Intracerebral Hemorrhage Onset Research Articles

Parental Influence on Intracerebral Hemorrhage Onset in Hereditary Dutch-Type Cerebral Amyloid Angiopathy.

Dutch-type cerebral amyloid angiopathy (D-CAA) is an autosomal dominant hereditary form of CAA causing intracerebral hemorrhage (ICH) and cognitive decline. The age of onset of ICH in D-CAA mutation carriers is strikingly variable and ranges from late thirties up to 70 years. We investigated the presence of genetic anticipation and assessed the influence of parental age at onset and sex on age of ICH onset in offspring. We included (potential) D-CAA mutation carriers from our prospective D-CAA family database. Participants were sent a questionnaire by mail and asked for the onset age of symptomatic ICH and the onset age of symptomatic ICH of their affected first-degree relative(s), their siblings and affected parent. We used a Cox regression model with the age of onset of the parent as the covariate and the sex of the offspring as the factor. Next, we replaced the sex of the offspring with a factor with four levels: mother/daughter, mother/son, father/daughter, and father/son. We used a random effect per household. A total of 66 respondents completed the questionnaire. Reported mean age of first symptomatic ICH was similar (both 52 years, p = 0.87) for D-CAA parents (n = 60) and their offspring (n = 100). Offspring with a mother with D-CAA seemed to have an earlier ICH onset (50 years, standard deviation [SD] ± 7) than offspring with a paternal inheritance (54 years, SD ± 6, p = 0.03). There was no association between onset of first ICH of the parent and offspring after adding sex of the offspring to the Cox regression model: hazard ratio 0.99, 95% CI: 0.94-1.03, p = 0.51. The interaction between parent's sex and child's sex was not significant (p = 0.70). The results with and without random effect were essentially identical. We found no indication for genetic anticipation in D-CAA in general, although maternal inheritance seemed to be associated with an earlier ICH onset.

Protective effects of flavonoids against intracerebral and subarachnoid hemorrhage (Review).

Intracerebral hemorrhage (ICH), known as non-traumatic cerebrovascular rupture and hemorrhage, often occurs in the deep basal brain segment. It is known for its high morbidity and mortality rates. Subarachnoid hemorrhage (SAH) is a clinical syndrome caused by the rupture of blood vessels at the base or surface of the brain that allows blood to flow directly into the subarachnoid space. It progresses quickly and typically manifests at younger ages compared with ICH. ICH and SAH are both devastating events in the category of hemorrhagic strokes and are attracting increasing attention from researchers. Flavonoids, being important natural molecules, have remarkable anti-inflammatory and antioxidant effects. Flavonoids have extensive biological activities in inflammation and oxidative stress (OS), and have protective effects in vascular function associated with cerebrovascular diseases. They have an impact on the onset of ICH and SAH by targeting various pathways, including the suppression of inflammation and OS. Recently, the role of flavonoid compounds in ICH and SAH has also received increasing interest. Thus, to serve as a resource for the prevention and treatment of ICH and SAH, the present review provided an overview of the research on flavonoid compounds in the prevention of brain damage after these two conditions have occurred.

The Role of Aging in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is the cerebrovascular disease with the highest disability and mortality rates, causing severe damage to the health of patients and imposing a significant socioeconomic burden. Aging stands as a foremost risk factor for ICH, with a significant escalation in ICH incidence within the elderly demographic, highlighting a close association between ICH and aging. In recent years, with the acceleration of the "aging society" trend, exploring the intricate relationship between aging and ICH has become increasingly urgent and worthy of in-depth attention. We have summarized the characteristics of ICH in the elderly, reviewing how aging influences the onset and development of ICH by examining its etiology and the mechanisms of damage via ICH. Additionally, we explored the potential impacts of ICH on accelerated aging, including its effects on cognitive abilities, quality of life, and lifespan. This review aims to reveal the connection between aging and ICH, providing new ideas and insights for future ICH research.

Sex differences in histopathological markers of cerebral amyloid angiopathy and related hemorrhage.

Men with cerebral amyloid angiopathy (CAA) may have an earlier onset of intracerebral hemorrhage and a more hemorrhagic disease course compared to women. In this cohort study, we investigated sex differences in histopathological markers associated with amyloid-β burden and hemorrhage in cognitively impaired individuals and patients with CAA, using neuropathological data from two autopsy databases. First, we investigated presence of parenchymal (Thal score) and vascular amyloid-β (CAA severity score) in cognitively impaired individuals from the National Alzheimer's Coordinating Center (NACC) neuropathology database. Next, we examined sex differences in hemorrhagic ex vivo magnetic resonance imaging (MRI) markers and local cortical iron burden and the interaction of sex on factors associated with cortical iron burden (CAA percentage area and vessel remodeling) in patients with pathologically confirmed clinical CAA from the Massachusetts General Hospital (MGH) CAA neuropathology database. In 6120 individuals from the NACC database (45% women, mean age 80 years), the presence of parenchymal amyloid-β (odds ratio (OR) (95% confidence interval (CI)) =0.68 (0.53-0.88)) but not vascular amyloid-β was less in men compared to women. In 19 patients with definite CAA from the MGH CAA database (35% women, mean age 75 years), a lower microbleed count (p < 0.001) but a higher proportion of cortical superficial siderosis and a higher local cortical iron burden was found in men (p < 0.001) compared to women. CAA percentage area was comparable in men and women (p = 0.732). Exploratory analyses demonstrated a possible stronger negative relation between cortical CAA percentage area and cortical iron density in men compared to women (p = 0.03). Previously observed sex differences in hemorrhage onset and progression in CAA patients are likely not due to differences in global CAA severity between men and women. Other factors, such as vascular remodeling, may contribute, but future studies are necessary to replicate our findings in larger data sets and to further investigate the underlying mechanisms behind these complex sex differences.

Antithrombotic Treatment and Clinical Outcomes After Intracerebral Hemorrhage: A Retrospective Cohort Study from the Swedish Stroke Register.

A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH. We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence. There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.

The relationship between perihematomal edema and hematoma expansion in acute spontaneous intracerebral hemorrhage: an exploratory radiomics analysis study.

The relationship between early perihematomal edema (PHE) and hematoma expansion (HE) is unclear. We investigated this relationship in patients with acute spontaneous intracerebral hemorrhage (ICH), using radiomics. In this multicenter retrospective study, we analyzed 490 patients with spontaneous ICH who underwent non-contrast computed tomography within 6 h of symptom onset, with follow-up imaging at 24 h. We performed HE and PHE image segmentation, and feature extraction and selection to identify HE-associated optimal radiomics features. We calculated radiomics scores of hematoma (Radscores_HEA) and PHE (Radscores_PHE) and constructed a combined model (Radscore_HEA_PHE). Relationships of the PHE radiomics features or Radscores_PHE with clinical variables, hematoma imaging signs, Radscores_HEA, and HE were assessed by univariate, correlation, and multivariate analyses. We compared predictive performances in the training (n = 296) and validation (n = 194) cohorts. Shape_VoxelVolume and Shape_MinorAxisLength of PHE were identified as optimal radiomics features associated with HE. Radscore_PHE (odds ratio = 1.039, p = 0.032) was an independent HE risk factor after adjusting for the ICH onset time, Glasgow Coma Scale score, baseline hematoma volume, hematoma shape, hematoma density, midline shift, and Radscore_HEA. The areas under the receiver operating characteristic curve of Radscore_PHE in the training and validation cohorts were 0.808 and 0.739, respectively. After incorporating Radscore_PHE, the integrated discrimination improvements of Radscore_HEA_PHE in the training and validation cohorts were 0.009 (p = 0.086) and -0.011 (p < 0.001), respectively. Radscore_PHE, based on Shape_VoxelVolume and Shape_MinorAxisLength of PHE, independently predicts HE, while Radscore_PHE did not add significant incremental value to Radscore_HEA.

Rationale and Design of the Statin Use in Intracerebral Hemorrhage Patients (SATURN) Trial

Introduction: The benefits and risks of HMG-CoA reductase inhibitor (statin) drugs in survivors of intracerebral hemorrhage (ICH) are unclear. Observational studies suggest an association between statin use and increased risk of lobar ICH, particularly in patients with apolipoprotein-E (APOE) ε2 and ε4 genotypes. There are no randomized controlled trials addressing the effects of statins after ICH leading to uncertainty as to whether statins should be used in patients with lobar ICH who are at high risk for ICH recurrence. The SATURN trial aims to evaluate the effects of continuation versus discontinuation of statin on the risk of ICH recurrence and ischemic major adverse cerebro-cardio-vascular events (MACCEs) in patients with lobar ICH. Secondary aims include the assessment of whether the APOE genotype modifies the effects of statins on ICH recurrence, functional and cognitive outcomes, and quality of life. Methods: The SATURN trial is a multi-center, pragmatic, prospective, randomized, open-label, phase III clinical trial with blinded end-point assessment. A planned total of 1,456 patients with lobar ICH will be recruited from 140 sites in the USA, Canada, and Spain. Patients presenting within 7 days of a spontaneous lobar ICH that occurred while taking a statin will be randomized (1:1) to continuation (control) versus discontinuation (intervention) of the same statin drug and dose that they were using at ICH onset. The primary outcome is the time to recurrent symptomatic ICH within a 2-year follow-up period. The primary safety outcome is the occurrence of ischemic MACCE. Conclusion: The results will help to determine the best strategy for statin use in survivors of lobar ICH and may help to identify if there is a subset of patients who would benefit from or be harmed by statins.

Risk factors for intracerebral hemorrhage in small-vessel disease and non-small-vessel disease etiologies-an observational proof-of-concept study.

Sporadic cerebral small-vessel disease (CSVD), i.e., hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), is the main cause of spontaneous intracerebral hemorrhage (ICH). Nevertheless, a substantial portion of ICH cases arises from non-CSVD etiologies, such as trauma, vascular malformations, and brain tumors. While studies compared HA- and CAA-related ICH, non-CSVD etiologies were excluded from these comparisons and are consequently underexamined with regard to additional factors contributing to increased bleeding risk beyond their main pathology. As a proof of concept, we conducted a retrospective observational study in 922 patients to compare HA, CAA, and non-CSVD-related ICH with regard to factors that are known to contribute to spontaneous ICH onset. Medical records (available for n = 861) were screened for demographics, antithrombotic medication, and vascular risk profile, and CSVD pathology was rated on magnetic resonance imaging (MRI) in a subgroup of 185 patients. The severity of CSVD was assessed with a sum score ranging from 0 to 6, where a score of ≥2 was defined as advanced pathology. In 922 patients with ICH (median age of 71 years), HA and CAA caused the majority of cases (n = 670, 73%); non-CSVD etiologies made up the remaining quarter (n = 252, 27%). Individuals with HA- and CAA-related ICH exhibited a higher prevalence of predisposing factors than those with non-CSVD etiologies. This includes advanced age (median age: 71 vs. 75 vs. 63 years, p < 0.001), antithrombotic medication usage (33 vs. 37 vs. 19%, p < 0.001), prevalence of vascular risk factors (70 vs. 67 vs. 50%, p < 0.001), and advanced CSVD pathology on MRI (80 vs. 89 vs. 51%, p > 0.001). However, in particular, half of non-CSVD ICH patients were either aged over 60 years, presented with vascular risk factors, or had advanced CSVD on MRI. Risk factors for spontaneous ICH are less common in non-CSVD ICH etiologies than in HA- and CAA-related ICH, but are still frequent. Future studies should incorporate these factors, in addition to the main pathology, to stratify an individual's risk of bleeding.

Sex Differences in the Epidemiology of Intracerebral Hemorrhage Over 10 Years in a Population-Based Stroke Registry.

We investigated incidence and outcome of spontaneous intracerebral hemorrhage (ICH) in a population-based stroke registry and provided data to inform on the figures of the disease in women and in men. Our prospective population-based registry included patients with first-ever ICH occurring from January 2011 to December 2020. Incidence rates were standardized to the 2011 Italian and European population, and incidence rate ratios were calculated. Multivariate hazard ratios for 30-day and 1-year fatality were estimated with Cox regression, including components of the ICH score and sex. We included 748 first-ever ICHs (41.3% women). Women were significantly older than men at ICH onset (78.9±12.6 versus 73.2±13.6 years; P<0.001) and showed higher clinical severity on presentation (median National Institutes of Health Stroke Scale score, 11 [interquartile range, 6-20] versus 9 [interquartile range, 4-15], respectively; P=0.016). The crude annual incidence rate was 20.2 (95% CI, 18.0-22.6) per 100 000 person-years in women and 30.2 (95% CI, 27.4-33.2) per 100 000 person-years in men); incidence was lower in women versus men (incidence rate ratio, 0.67 [95% CI, 0.58-0.78]; P<0.001) and did not change over time in both sexes (P for trend=0.073 and 0.904, respectively). Unadjusted comparison showed higher 1-year case-fatality rates in women versus men (48.5% versus 40.1%; P=0.026). After adjusting for components of the ICH score, female sex lost significance as a predictor of mortality. We found lower ICH incidence in women than in men. However, women showed a higher 1-year case-fatality rate versus men, which was likely related to older age at ICH onset and higher clinical severity. Identification of factors explaining the reported differences is important to develop targeted interventions.

Long-term headache after spontaneous intracerebral haemorrhage.

Though headache is commonly observed after stroke and may affect survivors' quality of life, it has rarely been studied after spontaneous intracerebral haemorrhage (ICH). In a cohort of ICH survivors, we assessed the long-term prevalence and determinants of headache. We screened consecutive ICH survivors enrolled in the prospective, single-centre Prognosis of Intracerebral Haemorrhage study for headache 1, 3, and 6 years after ICH, according to the International Headache Society's criteria. Depressive and anxiety symptoms severity was measured at 1-year follow-up. Variables associated with the presence of headache 1 year after ICH were analyzed using univariate and multivariable models. Among the 146 patients included in this study, 31 (21%), 25 (19%), and 14 (20%) patients reported headache at 1-, 3-, and 6-year follow-up, respectively. In an age-adjusted model, patients with headache at ICH onset (adjusted odds ratio [aOR] 2.75; 95% CI 1.02-7.42) and previous history of headache (aOR 4.60; 95% CI 1.74-12.1) were associated with headache at 1-year follow-up. Patients with headache were more likely to report depressive and anxiety symptoms at 1-year follow-up (both p < 0.02). One in five ICH survivors suffered from headache and patients who reported headache at ICH onset were especially at risk.

Abstract WP176: Hemoglobin Decrement is Associated With Ischemic Lesions on Brain MRI of Patients With Acute Intracerebral Hemorrhage

Background: We have previously identified that hemoglobin decrements and new-onset anemia during an intracerebral hemorrhage (ICH) hospitalization is frequent, rapid, and associates with poor outcome. Though this association may be related to impaired cerebral oxygen delivery, it is unclear whether these changes relate to cerebral ischemia. We investigated the relationship of hemoglobin decrements over time and ischemic lesions on brain MRI during an ICH hospitalization. Methods: Consecutive patients with acute spontaneous ICH enrolled into a single-center, prospective cohort study between 2009 and 2019 were assessed. Patients who had a brain MRI and serial hemoglobin measurements were included. Change in hemoglobin from admission to date of brain MRI (delta Hgb) was defined as the exposure. The outcome was the presence of remote ischemic lesions, defined as foci of diffusion restriction &gt;10 mm away from the hematoma on brain MRI. A regression model assessed relationships between delta Hgb and DWI brain lesions, adjusting for baseline demographics, ICH severity, and time to MRI. Separate sensitivity models were adjusted for admission systolic blood pressure and hemoglobin. Results: We identified 189 ICH patients with brain MRI and serial hemoglobin measurements during their hospitalization. The mean age was 66.5 (SD 14.8) and 49.2% were female. Mean admission hemoglobin was 13.5 g/dL (SD 2.0), mean change in hemoglobin from admission to day of MRI was -1.6 (SD 1.6), median time from ICH onset to MRI was 2 (IQR 1-4) days, and 31.7% of patients had ischemic lesions on MRI. We identified an association of greater decrements in hemoglobin with ischemic lesions in our primary model (adjusted OR 0.79, 95%CI 0.64-0.99, p=0.04). Sensitivity analyses adjusting for admission systolic blood pressure and hemoglobin did not change this association. Conclusions: Greater hemoglobin decrements associate with remote ischemic lesions on brain MRI of patients with acute ICH. Further work is needed to assess drivers of anemia after ICH and possible causal mechanisms for ischemic brain injury to assess whether anemia is a modifiable treatment target to improve ICH outcomes.

Abstract NS3: Nurse Led Interventions Improve the Timeliness of Blood Pressure Reduction in Patients Presenting With Acute Nontraumatic Intracerebral Hemorrhage

Introduction: The 2022 AHA/ASA Guidelines for Intracerebral Hemorrhage (ICH) recommend initiating treatment and lowering blood pressure (BP) within 2 hours of ICH onset and reaching the target systolic BP of 130-150mmHg within one hour of treatment initiation. This study evaluates the effectiveness of nursing education at a Comprehensive Stroke Center (CSC) on improving the timeliness of BP medication administration and BP reduction in ICH patients. Methods: Emergency Department (ED) code stroke patients with a diagnosis of ICH were included in the analysis from 6/2022-12/2022 (pre-intervention) and 1/2023-6/2023 (post-intervention). Guideline based education regarding the importance of timely medication administration was provided in nursing huddles. Nurse to patient ratios were changed to 1:1 until goal BP achieved. BP medications were also placed in the CT scanner pyxis for immediate access. Baseline demographics, NIHSS, ICH score, and door to blood pressure reduction related time metrics were collected. Data were analyzed using R package. Results: 34 patients were analyzed, 12 (35%) pre and 22 (65%) post-intervention. Patient demographics and characteristics were not different between both groups (Table 1). Time from first BP medication order to BP in range improved: 62(46.7-80) vs 43(33-52.3) mins p=0.02. In addition, the time from door to Systolic BP 130-150mmHg improved 81 (68.5-91.3) vs 56 (37.38-73.5) mins p=0.02 (Table 2). Conclusion: Guideline based education is effective in promoting nursing-led interventions to achieve timely BP reduction of ICH patients to the target goal of 130-150 mmHg.

Time-Dependent Changes in Hematoma Expansion Rate after Supratentorial Intracerebral Hemorrhage and Its Relationship with Neurological Deterioration and Functional Outcome.

Hematoma expansion (HE) following an intracerebral hemorrhage (ICH) is a modifiable risk factor and a treatment target. We examined the association of HE with neurological deterioration (ND), functional outcome, and mortality based on the time gap from onset to baseline CT. We included 567 consecutive patients with supratentorial ICH and baseline head CT within 24 h of onset. ND was defined as a ≥4-point increase on the NIH stroke scale (NIHSS) or a ≥2-point drop on the Glasgow coma scale. Poor outcome was defined as a modified Rankin score of 4 to 6 at 3-month follow-up. The rate of HE was higher among those scanned within 3 h (124/304, 40.8%) versus 3 to 24 h post-ICH onset (53/263, 20.2%) (p < 0.001). However, HE was an independent predictor of ND (p < 0.001), poor outcome (p = 0.010), and mortality (p = 0.003) among those scanned within 3 h, as well as those scanned 3-24 h post-ICH (p = 0.043, p = 0.037, and p = 0.004, respectively). Also, in a subset of 180/567 (31.7%) patients presenting with mild symptoms (NIHSS ≤ 5), hematoma growth was an independent predictor of ND (p = 0.026), poor outcome (p = 0.037), and mortality (p = 0.027). Despite decreasing rates over time after ICH onset, HE remains an independent predictor of ND, functional outcome, and mortality among those presenting >3 h after onset or with mild symptoms.

Prevalence, clinical characteristics, and risk factors of intracerebral haemorrhage in CADASIL: a case series and systematic review

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by early onset stroke and dementia. Most strokes are lacunar ischaemic strokes, but intracerebral haemorrhage (ICH) has also been reported, although there are limited published data on its frequency and characteristics.MethodsA retrospective review of a prospectively recruited CADASIL register from the British National Referral clinic was performed to identify acute ICH cases and their characteristics. In addition, a systematic review of ICH in CADASIL was performed. MEDLINE (Pubmed), Embase, and Web of Science were searched for articles published from inception until 31/05/2023.ResultsTen cases of ICH were identified from the National clinic register of 516 symptomatic patients, giving an estimated point prevalence of 1.9%. An additional 119 cases were identified from the systematic review, comprising 129 cases and 142 ICH events in total. Including all identified cases, the mean age at onset of ICH was 56.6 ± 15.7 (SD) years, and 74 (57.4%) were male. ICH was the first manifestation of the disease in 32 patients (38.1%), and ICH recurrence occurred in 16 (12.4%). Most ICHs were subcortical, with the thalamus, 58 (40.8%), and basal ganglia, 34 (23.9%), being the commonest sites. Anticoagulation, but not antiplatelet agents, was associated with an increased risk of ICH (20.0% vs. 1.9%, p = 0.006).ConclusionsICH is a relatively rare manifestation of CADASIL, occurring in about 2% of symptomatic cases. Most of the haemorrhages occurred in the subcortical regions.

Clearance of Neutrophils From ICH-Affected Brain by Macrophages Is Beneficial and Is Assisted by Lactoferrin and CD91.

Within hours after intracerebral hemorrhage (ICH) onset, masses of polymorphonuclear neutrophils (PMNs) infiltrate the ICH-affected brain. After degranulation involving controlled release of many toxic antimicrobial molecules, the PMNs undergo rapid apoptosis and then are removed by phagocytic microglia/macrophages (MΦ) through a process called efferocytosis. Effective removal of PMNs may limit secondary brain damage and inflammation; however, the molecular mechanisms governing these cleanup activities are not well understood. We propose that scavenger receptor CD91 on myeloid phagocytes especially in presence of CD91 ligand, LTF (lactoferrin, protein abundant in PMNs), plays an important role in clearance of dead apoptotic PMNs (ANs). Mice/rats were subjected to an autologous blood injection model of ICH. Primary cultured microglia were used to assess phagocytosis of ANs. Immunohistochemistry was employed to assess CD91 expression and PMN infiltration. CD91 knockout mice selectively in myeloid phagocytes (Mac-CD91-KO) were used to establish the CD91/LTF function in phagocytosis and in reducing ICH-induced injury, as assessed using behavioral tests, hematoma resolution, and oxidative stress. Masses of PMNs are found in ICH-affected brain, and they contain LTF. MΦ at the outer border of hematoma are densely packed, expressing CD91 and phagocytosing ANs. Microglia deficient in CD91 demonstrate defective phagocytosis of ANs, and mice deficient in CD91 (Mac-CD91-KO) subjected to ICH injury have increased neurological dysfunction that is associated with impaired hematoma resolution (hemoglobin and iron clearance) and elevated oxidative stress. LTF that normally ameliorates ICH injury in CD91-proficient control mice shows reduced therapeutic effects in Mac-CD91-KO mice. Our study suggests that CD91 plays a beneficial role in improving ANs phagocytosis and ultimately post-ICH outcome and that the beneficial effect of LTF in ICH is in part dependent on presence of CD91 on MΦ.

ABO-Incompatible Platelet Transfusion Is Associated with Ischemic Lesions on Brain MRI in Patients with Intracerebral Hemorrhage

Background: We have identified that major ABO-incompatible platelet transfusions are associated with poor intracerebral hemorrhage (ICH) outcomes. The underlying drivers for the relationship of these incompatible platelet units on outcome are unknown, yet do not appear to be related to impaired hemostasis. Conversely, ICH patients are known to encounter remote, “silent” ischemic lesions, thought to be from microthrombosis, during their hospitalization. Though these ischemic lesions are well known to associate with poor ICH outcomes, risk factors for its formation are unknown. We explored whether major ABO-incompatible platelet transfusions are associated with acute ischemic lesions on brain MRI during an ICH hospitalization. Methods: Consecutive spontaneous ICH patients enrolled into a single-center, prospective cohort study between 2009 and 2018 were assessed. Patients who received a single platelet transfusion within 24 hours of ICH admission and had a brain MRI during the hospitalization were included in the analysis. Major ABO incompatible platelet transfusion (vs minor mismatch/identical) was defined as the exposure. Presence of remote ischemic lesions, defined as diffusion restriction &amp;gt;10 mm away from the hematoma detected on brain MRI, was the outcome. Regression models were used to assess relationships between major ABO-incompatible platelet unit exposure and acute ischemic brain lesions, adjusting for time from ICH onset to MRI or ICH severity. Results: We identified 40 ICH patients receiving an acute platelet transfusion and having a brain MRI performed during the ICH hospitalization. The mean age was 67.1 (SD 14.1), 37.5% were female, and 20% received a major ABO incompatible platelet unit. Patients receiving a major incompatible platelet unit were more likely to encounter ischemic lesions (62.5% vs 21.9%). We also identified an association of major ABO-incompatible platelets units with acute ischemic brain lesions in our regression models after adjusting for time from ICH symptom onset to MRI (OR 5.45, 95%CI 1.01-29.30, p=0.048) and ICH severity (OR 9.15, 95%CI 1.37-62.67, p=0.024). Additional sensitivity analysis adjusting for patient blood type did not alter this relationship (OR 17.1, 95%CI 1.34-217.9, p = 0.029). Conclusions: Among ICH patients receiving acute platelet transfusions and MRI neuroimaging, major ABO incompatible units were associated with remote ischemic lesions on brain MRI. Further work is needed to address the generalizability of our data and to clarify relationships of platelet unit characteristics, cerebral microthrombosis, and clinical outcomes after ICH.

Association between systolic blood pressure variability and severity of cerebral amyloid angiopathy in incident intracerebral hemorrhage

IntroductionThe role of systolic blood pressure (SBP) variability in the pathogenesis of cerebral amyloid angiopathy (CAA) as an underlying cause of intracerebral hemorrhage (ICH) is unknown. We studied SBP variability before ICH according to CAA severity at autopsy.MethodsWe collected office (primary care or hospital clinic) BP readings during 10 years before first-ever ICH onset in adults who died and had brain research autopsy in the Lothian IntraCerebral Hemorrhage, Pathology, Imaging, and Neurological Outcome (LINCHPIN), prospective, population-based, inception cohort study. A neuropathologist assessed CAA severity using a histopathological rating scale, masked to BP readings. Functional principal component analysis was used to model SBP levels by time before ICH, and logistic regression models assessed associations of SBP variability indices with CAA severity (moderate-severe vs. absent-mild) adjusted for age, gender, and mean SBP.ResultsAmong 72 adults (median age 81 [interquartile range 76–86], 56% female, median number of SBP readings 11 [3–19]), patients with moderate-severe CAA had similar mean SBP (143 vs. 145 mmHg, P = 0.588) but lower SBP variability (SBP standard deviation [SD] 14 vs. 17 mmHg, P = 0.033) compared with patients with absent-mild CAA, and their SBP trajectories seemed to differ over 10 years before ICH. The odds of moderate-severe CAA were higher with lower maximum SBP (adjusted OR per 10 mmHg lower: 1.53, 95% confidence interval [CI] 1.09–2.15; P = 0.015) and lower SBP range (1.29 [1.03–1.61]; P = 0.028), but not SBP SD (1.95 [0.87–4.38]; P = 0.11).DiscussionCompared with absent-mild autopsy-verified CAA, moderate-severe CAA is associated with lower maximum and range of pre-morbid SBP.

Resumption of oral anticoagulation in patients with non-valvular atrial fibrillation after intracerebral hemorrhage: A sub-analysis of the PASTA registry study

PurposeTo investigate the rate and timing of oral anticoagulant (OAC) resumption and its safety in patients after intracerebral hemorrhage (ICH) in current clinical practice in Japan. MethodsWe conducted a sub-analysis of the PASTA registry, an observational, multicenter registry of 1043 patients with stroke receiving OACs in Japan, by including patients with ICH on OAC treatment for non-valvular atrial fibrillation (NVAF). The clinical characteristics of the patients in the resumption and non-resumption groups, rate and timing of OAC resumption, its safety, and switching of OACs after ICH were investigated. ResultsOf the 160 patients (women, n = 52; median age, 77 years) included, OACs were resumed in 108 (68%) at a median of 7 days (interquartile range, 4–11) after acute ICH onset. The non-resumption group had higher rates of hematoma expansion (21.2% vs. 7.4%; P = 0.0118) and modified Rankin Scale (mRS) scores at discharge (4 (Suda et al., 2019; Steiner et al., 2014 [3, 4]) vs. 4 (Suda et al., 2019; Steiner et al., 2014; Pasquini et al., 2014 [3–5]); P = 0.0302}. The resumption rate in the mRS 0–4 group was higher than that in the mRS 5 group (75.2% vs. 46.5%; P = 0.00006). The number of days to resumption after ICH onset was longer in the mRS 5 than that in the mRS 0–4 group (median 12 days vs. 7 days, P = 0.0065). There were no significant differences in new-onset ICH, symptomatic hematoma expansion, or gastrointestinal bleeding between groups (P > 0.05). ConclusionsEarly resumption of OAC for NVAF in patients after ICH appeared to be safe. Expected functional outcomes at discharge were associated with OAC resumption and with the timing of resumption. Registrationhttps://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958

Prognostic value of day-of-event serum calcium and magnesium for predicting 1-year prognosis after intracerebral hemorrhage.

To investigate whether serum calcium and magnesium on the day of symptom onset contribute to prognosis at 1year after intracerebral hemorrhage (ICH). We prospectively enrolled patients admitted < 24h after symptom onset of primary ICH to West China Hospital between January 2012 and October 2014. Blood samples were collected at admission to determine the concentration of serum calcium and magnesium. We analyzed associations of the serum concentration of calcium and magnesium with unfavorable outcome (defined as modified Rankin scale, mRS ≥ 3) at 1year. We included 874 patients (mean age 59.1 ± 13.5years, 67.6% males), of whom 470 patients had mRS ≥ 3 and 284 patients died at 1year. Compared to patients with the highest tertile level of calcium concentration (≥ 2.29mmol/L), patients in the lowest tertile (≤ 2.15mmol/L) had higher odds of unfavorable outcome (odds ratio, OR 1.61, 95% confidence interval [CI] 1.04-2.50, P = 0.034). The Kaplan-Meier survival curve revealed a significant difference of cumulative survival rate across calcium tertiles (log-rank P value = 0.038). There was no significant association between serum concentration of magnesium and functional outcome at 1year. A reduced serum concentration of calcium on the day-of-event was associated with unfavorable outcome at 1year after ICH. Future studies are needed to illustrate the pathophysiological mechanism of calcium and whether calcium could be a treatment target for improving outcomes after ICH.

Interaction between cerebral small vessel disease, blood pressure, and remote ischemic lesions in acute spontaneous intracerebral hemorrhage.

Acute blood pressure (BP) reduction is the first-line treatment for acute spontaneous intracerebral hemorrhage (ICH); however, recent research suggests that intensive BP reduction along with cerebral small vessel disease (cSVD) is a risk factor for remote DWI lesions (RDWILs). We aimed to delineate the interplay between cSVD and BP reduction therapy on the risk of RDWILs. We enrolled 303 patients who underwent brain magnetic resonance imaging within 7 days after acute spontaneous ICH. RDWILs were categorized as occurring in borderzone (BZ) or non-BZ areas. We examined the effect of cSVD, acute BP reduction, and their interaction on RDWILs. RDWILs were observed in 34 (11%) patients (59.8 ± 10.3-years-old, 24% male). RDWILs were associated with a larger acute weighted average mean arterial pressure (MAP) reduction in the initial 24 h after ICH onset and a higher total cerebral microbleed (CMB) count. Intensive MAP changes (odds ratio (OR) per 10 mmHg 1.76, 95% confidence interval (CI) 1.03-3.20), total CMBs burden (OR per 10 CMBs 1.21, 95% CI 1.08-1.39), and presence of lobar CMBs (OR 7.33, 95% CI 1.59-55.6) were risk factors for RDWILs at BZ, but not at non-BZ. Furthermore, a significant interaction was observed between lobar CMBs and MAP reduction on increased risk of RDWILs at BZ (p = 0.030). cSVD modulates the effect of acute BP reduction on the risk of RDWILs. Patients with extensive microangiopathy have a higher risk of developing cerebral ischemic changes in BZ during unstable hemodynamic status.