Lobar Intracerebral Hemorrhage Research Articles

Medial intracranial carotid artery calcifications and hematoma expansion in deep intracerebral hemorrhage.

Medial intracranial carotid artery calcifications (ICAC) are associated with impaired vascular physiology, increased arterial stiffness and pulse pressure. Their presence might therefore be associated with increased risk of intracerebral hemorrhage (ICH) expansion, according to the avalanche model. We explored the association between ICAC presence and pattern and hematoma expansion (HE). Retrospective analysis of a monocentric, prospectively collected cohort of ICH patients admitted between June 2017 and October 2023. ICAC pattern was determined by Kockelkoren's rating scale on admission CT; medial ICAC were defined with a >6 points cutoff. A follow-up CT scan was performed within 72 h. HE was analyzed as a dichotomous (≥6 mL and/or ≥33%) and as a categorical (none/mild/moderate/severe) variable, and its predictors were explored with logistic and ordinal regression respectively, accounting for baseline volume, onset-to-CT time, and anticoagulation. All the analyses were stratified by ICH location (supratentorial deep vs lobar ICH). A total of 201 patients were included (median age 78, 42% females, 59% deep ICH). Medial ICAC were significantly more common in deep ICH with HE compared with non-expanders (72% vs 49%, p = 0.03), whereas there was no association between ICAC and HE in lobar ICH (53% vs 52%, p = 0.85). This association between medial ICAC and HE in deep ICH remained significant in logistic (aOR 3.11, 95% CI [1.19-9.06], p = 0.03) and ordinal regression (acOR 2.42, 95% CI [1.19-4.99], p = 0.01). Ipsilateral medial ICAC are associated with higher odds of HE in deep ICH. Our findings are best interpreted as hypothesis generating, requiring prospective validation and further research to characterize the underlying biological mechanisms.

Comparing white and gray matter responses to lobar intracerebral hemorrhage in piglets and the effects of deferoxamine

BackgroundIntracerebral hemorrhage (ICH) often impacts patient white matter. However, preclinically, the effects of ICH are mostly studied in rodents with sparse white matter. This study used a lobar porcine ICH model to examine differences in the effects of ICH on white and gray matter as well as the role of the iron chelator deferoxamine (DFX), on attenuation of such injury. MethodsThis two-part study was performed in piglets. Firstly, piglets had a needle (Sham) or 2.5 ml blood injection (ICH) and were euthanized at day 3. Secondly, animals were treated with vehicle or DFX after ICH and were euthanized at day 3. White and gray matter edema, the number of oligodendrocytes (mature and immature) and neurons, and the number of Perls' (iron), ferritin and heme oxygenase (HO)-1 positive cells were examined. ResultsAt day 3, ICH induced greater edema formation in white than gray matter. This marked white matter edema was associated with a loss of mature, but not immature, oligodendrocytes. ICH also induced neuronal death in gray matter. There were also marked increases in Perls', ferritin and HO-1 positive cells after ICH in both white and gray matter, but significantly more in the former. DFX attenuated ICH-induced brain edema in white but not gray matter and this was associated with increased survival of mature oligodendrocytes. DFX also increased survival of neurons in the gray matter and it reduced the number of Perls', ferritin and HO-1 positive cells in both tissue types. ConclusionsWhile there were commonalities in perihematomal changes between white and gray matter after ICH, there was greater edema in white matter which may be linked to the susceptibility of mature oligodendrocytes to ICH injury. Similarly, while DFX reduced perihematomal iron overload in both white and gray matter, it only significantly reduced edema in white matter where it increased the number of mature oligodendrocytes.

Identification of Genetic Loci Associated With Intracerebral Hemorrhage Using a Multitrait Analysis Approach.

Genome-wide association studies (GWASs) have only 2 loci associated with spontaneous intracerebral hemorrhage (ICH): APOE for lobar and 1q22 for nonlobar ICH. We aimed to discover new loci through an analysis that combines correlated traits (multi-trait analysis of GWAS [MTAG]) and explore a gene-based analysis, transcriptome-wide association study (TWAS), and proteome-wide association study (PWAS) to understand the biological mechanisms of spontaneous ICH providing potential therapeutic targets. We use the published MTAG of ICH (patients with spontaneous intraparenchymal bleeding) and small-vessel ischemic stroke. For all ICH, lobar ICH, and nonlobar ICH, a pairwise MTAG combined ICH with traits related to cardiovascular risk factors, cerebrovascular diseases, or Alzheimer disease (AD). For the analysis, we assembled those traits with a genetic correlation ≥0.3. A new MTAG combining multiple traits was performed with those traits whose pairwise MTAG yielded new GWAS-significant single nucleotide polymorphisms (SNPs), with a posterior-probability of model 3 (GWAS-pairwise) ≥0.6. We perform TWAS and PWAS that correlate the genetic component of expression or protein levels with the genetic component of a trait. We use the ICH cohort from UK Biobank as replication. For all ICH (1,543 ICH, 1,711 controls), the mean age was 72 ± 2 in cases and 70 ± 2 in controls, and half of them were women. Replication cohort: 700 ICH and 399,717 controls. Novel loci were found only for all ICH (the trait containing lobar and nonlobar ICH), combining data of ICH and small vessel stroke, white matter hyperintensities volume, fractional anisotropy, mean diffusivity, and AD. We replicated 6 SNPs belonging to 2q33.2 (ICA1L, β = 0.20, SE = 0.03, p value = 8.91 × 10-12), 10q24.33 (OBFC1, β = -0.12, SE = 0.02, p value = 1.67 × 10-8), 13q34 (COL4A2, β = 0.02, SE = 0.02, p value = 2.34 × 10-11), and 19q13.32 (APOC1, β = -0.19, SE = 0.03, p value = 1.38 × 10-12; APOE, β = 0.21, SE = 0.03, p value = 2.70 × 10-11; PVRL2:CTB-129P6.4, β = 0.15, SE = 0.03, p value = 1.38 × 10-8); 2 genes (SH3PXD2A, Z-score = 4.83, p value = 6.67 × 10-7; and APOC1, Z-score: = 5.11, p value = 1.60 × 10-7); and ICA1L transcript (Z-score = 6.8, p value = 9.1 × 10-12) and protein levels (Z-score = -5.8, p value = 6.7 × 10-9). Our results reinforce the role of APOE in ICH risk, replicate previous ICH-associated loci (2q33 and 13q34), and point to new ICH associations with OBFC1, PVRL2:CTB-129P6.4, APOC1, and SH3PXD2A. Our study used data from European subjects, our main limitation. These molecules could be potential targets for future studies for modulating ICH risk.

Temporal and Spatial Clustering of Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA)-associated lobar intracerebral hemorrhage (ICH) has a high risk of recurrence, but the underlying mechanisms remain uncertain. We, therefore, aimed to characterize patterns of recurrent ICH. We investigated early recurrent ICH (≥1 recurrent ICH event within 90 days of the index event) and ICH clusters (≥2 ICH events within 90 days at any time point) in 2 large cohorts of consecutive patients with first-ever ICH and available MRI. In 682 included patients (median age 68 years, 40.3% female, median follow-up time 4.1 years), 18 (2.6%) had an early recurrent ICH, which was associated with higher age and CAA. In patients with probable CAA, the risk of early recurrent ICH was increased 5-fold within the first 3 months compared with during months 4-12 (hazard ratio 5.41, 95% CI 2.18-13.4) while no significant difference was observed in patients without CAA. In patients with an ICH cluster, we observed spatial clustering (recurrent ICH within close proximity of index ICH in 63.0%) and a tendency for multiple sequential hemorrhages (≥3 ICH foci within 3 months in 44.4%). Our data provide evidence of both temporal and spatial clustering of ICH in CAA, suggesting a transient and localized active bleeding-prone process.

Factors associated with cognitive impairment before intracerebral haemorrhage: community-based neuropathological study.

Little is known about whether clinical, radiological or neuropathological features are associated with cognitive impairment before intracerebral haemorrhage. We conducted a community-based cohort study of 125 adults with intracerebral haemorrhage (lobar n = 71, non-lobar n = 54) with consent to brain autopsy. We compared small vessel disease biomarkers on diagnostic CT head and neuropathological findings including neurofibrillary tangles and amyloid plaques in adults without cognitive impairment versus cognitive impairment without dementia versus dementia before intracerebral haemorrhage, stratified by lobar and non-lobar intracerebral haemorrhage. In non-lobar intracerebral haemorrhage, severe cortical atrophy was less common in those without cognitive impairment (8/36, 22%) and cognitive impairment without dementia (0/9, 0%) versus dementia (5/9, 56%); P = 0.008. Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder neurofibrillary tangle pathology measured by median Braak stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [interquartile range, 2-3] versus cognitive impairment without dementia 4 [2-6] versus dementia 5.5 [4-6]; P = 0.004; non-lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [1-2] versus dementia 5 [3-6]; P < 0.001). Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder amyloid plaque pathology measured by median Thal stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [2-3] versus dementia 2.5 [2-3.5]; P = 0.033; non-lobar intracerebral haemorrhage: no cognitive impairment 1 [0-1] versus cognitive impairment without dementia 0 [0-2] versus dementia 3 [2-3]; P = 0.002). Our findings suggest that irrespective of intracerebral haemorrhage location, adults with cognitive impairment before an intracerebral haemorrhage have more Alzheimer's disease neuropathologic change.

The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy

BackgroundCerebral amyloid angiopathy (CAA) is characterized by amyloid-β (Aβ) deposition in cerebral vessels, leading to lobar cerebral microbleeds (CMB) and intracerebral hemorrhages (ICH). Apolipoprotein J (ApoJ) is a multifunctional chaperone related to Aβ aggregation and clearance. Our study investigated the vascular impact of chronic recombinant human Apolipoprotein J (rhApoJ) treatment in a transgenic mouse model of β-amyloidosis with prominent CAA.MethodsTwenty-month-old APP23 C57BL/6 mice received 25 doses of rhApoJ (1 mg/kg) (n = 9) or saline (n = 8) intraperitoneally for 13 weeks, while Wild-type (WT) mice received saline (n = 13). Postmortem brains underwent T2*-weighted magnetic resonance imaging (MRI) to detect hemorrhagic lesions. Aβ levels and distribution, cerebral fibrinogen leakage, brain smooth muscle actin (sma), and plasma matrix metalloproteinases and inflammatory markers were analyzed after treatments. Additionally, plasma samples from 22 patients with lobar ICH were examined to determine the clinical relevance of the preclinical findings.ResultsrhApoJ-treated APP23 presented fewer cortical CMBs (50–300 μm diameter) (p = 0.012) and cortical larger hemorrhages (> 300 μm) (p = 0.002) than saline-treated mice, independently of Aβ brain levels. MRI-detected hemorrhagic lesions correlated with fibrinogen cerebral extravasation (p = 0.011). Additionally, rhApoJ-treated mice presented higher number of sma-positive vessels than saline-treated mice (p = 0.038). In rhApoJ-treated mice, human ApoJ was detected in plasma and in occasional leptomeningeal vessels, but not in the parenchyma, suggesting that its mechanism of action operates through the periphery. The administration of rhApoJ induced an increase in plasma Groα (p = 0.035) and MIP-1α (p = 0.035) levels, while lower MMP-12 (p = 0.046) levels, compared to the saline-treated group. In acute lobar ICH patients, MMP-12 plasma levels correlated with larger hemorrhage volume (p = 0.040) and irregular ICH shape (p = 0.036).ConclusionsChronic rhApoJ treatment in aged APP23 mice ameliorated CAA-related neurovascular damage by reducing the occurrence of CMB. We propose that rhApoJ may prevent blood-brain barrier (BBB) leakage and CMB appearance partly through circulating MMP-12 modulation.

Intracranial Drain-Related Intracerebral Hemorrhage in Two Sporadic Cerebral Amyloid Angiopathy Patients.

Alzheimer's disease and cerebral amyloid angiopathy (CAA) are often associated. Amyloid accumulation within leptomeningeal and small/median-sized cerebral blood vessels in CAA results in vessel fragility, leading to spontaneous leptomeningeal bleeding, lobar intracerebral hemorrhage (ICH) and cerebral microbleeds. CAA is also associated with non-traumatic subdural hematoma. The role of CAA-related vessel fragility in hemorrhagic complications after trauma, brain surgery, and intracranial drain insertion in CAA is unknown. We present two sporadic CAA patients with intracranial drain-related ICH, probably due to different underlying mechanisms, related to indirect and direct CAA-associated vessel fragility.

Genetically proxied IL-6 signaling and risk of Alzheimer's disease and lobar intracerebral hemorrhage: A drug target Mendelian randomization study.

Evidence suggests that higher C-reactive protein (CRP) is associated with lower risk of Alzheimer's disease (AD) and lobar intracerebral hemorrhage (ICH). Whether interleukin (IL)-6 signaling, an active pharmacological target upstream of CRP, is associated with these amyloid-related pathologies remains unknown. We used 26 CRP-lowering variants near the IL-6 receptor gene to perform Mendelian randomization analyses for AD (111,326 cases, 677,663 controls) and ICH (1545 cases, 1481 controls). We explored the effect of genetically proxied IL-6 signaling on serum, cerebrospinal fluid (CSF), and brain proteome (971 individuals). Genetically upregulated IL-6 receptor-mediated signaling was associated with lower risk of AD (OR per increment in serum logCRP levels: 0.87, 95% CI: 0.79-0.95) and lobar ICH (OR: 0.27, 95% CI: 0.09-0.89). We also found associations with 312, 77, and 79 brain, CSF, and plasma proteins, respectively, some of which were previously implicated in amyloid-clearing mechanisms. Genetic data support that CRP-lowering through variation in the gene encoding IL-6 receptor may be associated with amyloid-related outcomes. Genetic variants proxying IL-6 inhibition are associated with AD and lobar ICH risk.The variants are also associated with amyloid clearing-related proteomic changes.Whether pharmacologic IL-6 inhibition is linked to AD or lobar ICH merits further study.

Prevalence of Cerebral Amyloid Angiopathy Pathology and Strictly Lobar Microbleeds in East-Asian Versus Western Populations: A Systematic Review and Meta-Analysis.

Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer's disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH). We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models. We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P<0.0001). However, age was in general lower in the East-Asian cohorts. The prevalence of CAA neuropathology in the general population, cognitively normal elderly, patients with AD, and patients with (lobar) ICH is similar in East-Asian and Western countries. In East-Asian cohorts reflecting the general population, cognitively normal elderly, and patients with ICH, strictly lobar microbleeds were less prevalent, likely due to their younger age. Consideration of potential presence of CAA is warranted in decisions regarding antithrombotic treatment and potential new anti-amyloid-β immunotherapy as treatment for AD in East-Asian and Western countries alike.

The potential for minimally invasive intracerebral hemorrhage evacuation in routine healthcare: applicability of the ENRICH trial criteria to an unselected cohort

ObjectiveFollowing the favorable outcomes demonstrated by the Early MiNimally-invasive Removal of IntraCerebral Hemorrhage (ENRICH) trial in supratentorial intracerebral hemorrhage (ICH) patients treated with minimally invasive surgery (MIS), and considering the increasing interest in MIS, we aimed to assess the potential eligibility rate for ICH patients in Sweden.MethodsAll patients with spontaneous ICH in the Swedish Stroke Register (RS) during 2017–2020 in Skane county (1.37 million) were assessed. Baseline imaging was used for radiological characterization. Clinical data were obtained from RS. MIS eligibility in the total ICH population meeting ENRICH criteria were estimated and extrapolated to the Swedish population (10.5 million).ResultsOf 1,314 ICH patients, 5.9% met the ENRICH criteria for MIS (ICH volume 30–80 ml). Considering the ENRICH trial results indicating the effectiveness of MIS was mainly attributable to intervention for lobar hemorrhages, we determined that 2.8% of our ICH cohort in Sweden would be eligible for MIS. The estimated rate of neurosurgery for ICH could increase from the current 1.46–1.90 patients/100,000 population/year (in absolute numbers from 154 to 200 interventions out of 2,400 ICHs in Sweden annually).ConclusionsWe show that 2.8% of the Skane ICH population would be eligible for MIS if ENRICH criteria are employed for patients with lobar ICH, corresponding to a 29% increase of current surgical rates for ICH in Sweden. As MIS for ICH is not yet standard practice in Sweden, consideration for its implementation within the neurosurgical organization becomes essential to accommodate the anticipated increase in patient demand.

Nutrition markers and discharge outcome in deep and lobar intracerebral hemorrhage.

Malnutrition is common in stroke patients and has been associated with poor functional outcomes and increased mortality after stroke. Previous research on nutrition status and post-intracerebral hemorrhage (ICH) outcomes, however, is limited and conflicting. Monocenter study of patients with spontaneous deep or lobar ICH from a longitudinal cohort enrolling consecutive patients between 1994 and 2022. Nutrition status was assessed using admission body mass index (BMI), albumin, total bilirubin, cholesterol, c-reactive protein, hemoglobin a1c, high-density lipoprotein, hemoglobin, low-density lipoprotein, mean corpuscular volume, alanine transaminase, and triglycerides. Main outcome was favorable discharge outcome (mRS 0-2). Multivariable logistic regression was conducted with adjustment for baseline differences. Among 2170 patients, 1152 had deep and 1018 had lobar ICH. Overweight BMI was associated with higher odds of favorable discharge outcome in all (aOR = 3.01, 95% CI 1.59-5.69, p = 0.001) and lobar (aOR = 3.26, 95% CI 1.32-8.08, p = 0.011) ICH after adjustment for baseline differences. This association did not reach statistical significance in deep (aOR = 2.77, 95% CI 0.99-7.72, p = 0.052) ICH. No lab values were associated with functional outcome in all, deep, or lobar ICH after adjustment. Overweight BMI was associated with favorable discharge status after ICH. These findings could inform future studies to determine whether overweight BMI has a protective effect in ICH patients.

Obesity and hypertension mediate the effect of education on deep intracerebral hemorrhage: A Mendelian randomization study

BackgroundEducational attainment (EA) as a stable indicator of socioeconomic status has been confirmed to affect intracerebral hemorrhage (ICH), but the mechanism relating EA and ICH is still unknown. AimTo explore the causal relationship between EA and ICH through a bidirectional and two-step Mendelian randomization (MR) study. MethodsUsing summary-level Genome-wide Association Study using GWAS data FROM CASES AND CONTROLS of European ancestry, we performed bidirectional and two-step MR analyses to explore the causal relationship between educational attainment and ICH to understand the mediating influence of risk factors in this process. We also carried out subgroup analysis according to the different sites (deep and lobar) of ICH. A set of sensitivity analyses were performed to test valid MR assumptions. ResultsBidirectional MR analysis consistently demonstrated a unidirectional causal effect, revealing that higher EA had a protective influence on ICH. Each additional 1-standard deviation (SD) increase in genetically predicted years of schooling was associated with a reduced risk of all ICH (inverse variance weighted (IVW) OR: 0.381 [95 %CI: 0.264–0.549]), deep ICH (OR: 0.334 [95 %CI: 0.216–0.517]), and lobar ICH (OR: 0.422 [95 %CI: 0.261–0.682]). The mediating effect of EA on all ICH was mediated via systolic blood pressure (SBP) (6.93 % [1.20–13.45 %]) and body mass index (BMI) (17.87 % [3.92–34.64 %]), and the mediating effect of EA on deep ICH was also mediated via SBP (7.85 % [1.55–15.07 %]) and BMI (18.63 % [4.02–36.26 %]). ConclusionThis study provides robust genetic evidence for supporting the protective effect of EA on ICH risk, with further evidence that the effect of EA on deep ICH is partially mediated through hypertension and obesity. Further validation is needed to ascertain whether these findings are applicable to other racial or general population groups.

Characteristics of rehabilitation duration in patients with intracerebral hemorrhage

Background and PurposeNo consensus exists on the ideal duration of rehabilitation in patients with intracerebral hemorrhage (ICH). The aim of this study is to identify demographic and clinical characteristics associated with rehabilitation duration (RD) in patients with ICH during hospitalization. MethodsThis retrospective study followed consecutive patients admitted to a tertiary care center between 2016 and 2019 with primary diagnosis of ICH. The primary outcome, RD was calculated by adding the total number of therapy (speech, occupational, and physical) minutes received during admission, divided by the hospital length of stay. Variables abstracted included demographic and clinical characteristics (ICH score, neurosurgical procedure). Multiple linear regression models were used to measure adjusted association between select predictors and mean RD. ResultsA total of 316 ICH patients (62.5 ± 15.9 years, 49 % White) were included in the final analysis. Compared to Whites, other racial minorities (β= -9.017, p = 0.002) received rehabilitation therapy for a significantly shorter duration in the adjusted model. Age was significantly associated with having higher RD (β=0.320, p < 0.001). Patients with lobar ICH (β= -7.486, p = 0.014) had significantly shorter RD compared to deep. ICH score was significantly associated with having a lower RD (β= -8.624, p < 0.001). ConclusionAge, race, ICH score, and location were significantly associated with RD. Non-White patients had significantly shorter RD, indicating a potential racial disparity in the rehabilitation of patients with ICH.

Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage (P10-2.004)

Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage (P10-2.004)

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.

Minocycline in Severe Cerebral Amyloid Angiopathy: A Single-Center Cohort Study.

Evidence from animal studies suggests that minocycline may reduce lobar intracerebral hemorrhage (ICH) recurrence in cerebral amyloid angiopathy, possibly by inhibiting perivascular extracellular matrix degradation in cerebral small vessels. There is currently no evidence of its safety or efficacy in humans with cerebral amyloid angiopathy. To provide preliminary data to support future studies of minocycline's efficacy, the authors performed a retrospective single-center cohort study to assess the incidence of recurrent ICH in patients with an aggressive clinical course of probable cerebral amyloid angiopathy who had been prescribed minocycline off-label via shared decision-making. Crude incidence rate ratios were calculated to compare incidence rates before versus after treatment. Sixteen patients (mean age at minocycline initiation, 66.3±3.5 years; women 62.5%; median of 3 lobar ICHs [range, 1-6]) were initiated on minocycline and followed for a median of 12.4 months (range, 1.8-61.4 months). Adverse events were reported in 4 of 16 patients (gastroenteric, n=3; dizziness, n=1) and were considered mild. ICH incidence sharply increased the year before minocycline initiation compared with the preceding years (2.18 [95% CI, 1.50-3.07] versus 0.40 [95% CI, 0.25-0.60] events per patient-year) and fell to 0.46 (95% CI, 0.23-0.83) events per patient-year afterwards. Incidence rate ratios of recurrent ICH after minocycline was lower (0.21 [95% CI, 0.11-0.42], P<0.0001) compared with the year before initiation. Minocycline appeared safe and generally tolerated in a small group of patients with clinically aggressive cerebral amyloid angiopathy and was associated with reduced ICH recurrence. Determining whether this reduction represents a biological response to minocycline rather than a regression to the mean, however, will require a future controlled treatment trial.

Abstract 149: Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage

Background: Blood pressure (BP) reduction is associated with better neuroimaging and clinical outcomes in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). Because this evidence comes from studies that overwhelmingly enrolled deep hemorrhages, the impact of BP reduction in patients with lobar ICH remains understudied. Methods: We re-analyzed data from the pivotal Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) study. We included all patients with available neuroimaging data. Participants were randomized to either intensive (systolic BP target 110-139 mmHg) or standard (systolic BP target 140-179 mmHg) acute BP lowering. The main outcome measures were hematoma expansion &gt; 6 mL in the first 24 hours (HE), poor functional outcome (3-month mRS 4-6) and renal adverse events (RAE) until day 7 or hospital discharge. We fitted multivariable logistic regression models to test for association between the intervention and our outcomes of interest. Covariates included sex, age, race and ethnicity, and baseline ICH volume. Results: Among 1,000 patients enrolled in ATACH-2, 875 (87.5%) with complete data were included (88.9% deep hemorrhages and 11.1% lobar hemorrhages). The baseline characteristics of the intensive and standard treatment groups remained balanced as in the original study (all comparisons p &gt;0.05). Multivariable logistic regression showed that intensive BP reduction decreased the risk of HE (OR 0.60, 95%CI 0.39-0.90; p=0.02) and increased the risk of RAE (OR 2.53, 95%CI 1.40-4.77; p=0.003) in patients with deep, but not lobar ICH (HE, OR: 0.89; 95% CI= 0.31 - 2.52; p=0.83 and RAE, OR: 0.46; 95% CI= 0.04 - 5.10; p=0.53). Intensive BP reduction was not associated with improved mRS in either deep (OR: 0.96; 95 % CI= 0.68 - 1.37; p= 0.82) nor lobar (OR: 0.66; 95% CI= 0.16 - 2.42; p= 0.54) ICH. Conclusion: The impact of intensive blood pressure lowering differs in deep and lobar ICH. These results emphasize the need for a better understanding about biologic differences in ICH, which may have therapeutic implications.

Abstract TMP78: Disparities in Experiencing Major Adverse Cardiovascular Events Among Survivors of Spontaneous Intracerebral Hemorrhage by Hematoma Location

Background: Large studies evaluating the association of hematoma location with the risk of developing major adverse cardiovascular events (MACE) among survivors of intracerebral hemorrhage (ICH) in the United States are lacking. Methods: We identified adult (&gt;=18 years) ICH survivors from the state inpatient and the state emergency department databases of Florida, New York, Maryland, Washington, and Georgia (2016 - 2019). We fit a series of multivariable Fine-Gray sub-distribution hazard models, with the competing risk of death, and report the sub-distribution hazard ratio (SHR) and 95% confidence interval (CI) of the independent associations of hematoma location (lobar vs. non-lobar) with recurrent ICH (r-ICH), acute ischemic stroke (AIS), acute myocardial infarction (AMI), and MACE (any stroke, AMI, systemic embolism, or vascular death). Results: Among 10,652 ICH patients (median age [IQR]: 70 [58 - 80] years; 47.7% female; 43.2% lobar ICH), 3.3%, 3.1%, 0.5%, and 8.1%, respectively, experienced r-ICH, AIS, AMI, and MACE. Patients with lobar ICH (vs. non-lobar ICH) had a higher risk of r-ICH (SHR, CI: 1.67, 1.35 - 2.07) and MACE (1.28, 1.14 - 1.44). Blacks (vs. Whites) have a higher risk of AIS (1.64, 1.32 - 2.03) and MACE (1.42, 1.22 - 1.65). Also, privately insured patients (vs. Medicare) have a lower risk of r-ICH (0.45, 0.31 - 0.67), AIS (0.71, 0.53 - 0.95), and MACE (0.58, 0.47 - 0.71). Patients from low-income zip codes have a higher risk of AMI (1.83, 1.23 - 2.15) and MACE (1.16, 1.02 - 1.32). Patients with atrial fibrillation had a higher risk of AIS (1.47, 1.18 - 1.84) and MACE (1.26, 1.07 - 1.49). Patients with a high risk of metabolic syndrome (&gt;= 2 of the following: hypertension, diabetes, hyperlipidemia, or obesity) have a higher risk of AIS (1.37, 1.13 - 1.65), AMI (1.81, 1.19 - 2.75), and MACE (1.28, 1.13 - 1.44). Conclusions: Developing targeted secondary prevention strategies tailored to the specific sociodemographic and clinical profiles of ICH survivors is warranted.

Abstract TMP77: Oral Health as a Risk Factor for Spontaneous Intracerebral Hemorrhage: A Mendelian Randomization Analysis

Background: Poor oral health is a highly prevalent and modifiable risk factor that is associated with higher risk of cardiovascular disease, including ischemic stroke. However, the relationship between oral health and spontaneous intracerebral hemorrhage (ICH) has not been studied. We tested the hypothesis that genetically-determined poor oral health increases the risk of ICH. Methods: We conducted a two-sample Mendelian Randomization (MR) study using summary statistics from the largest genome-wide associations studies of oral health and ICH conducted to date. As genetic instruments (e.g., genetic risk variants for oral health), we identified 105 independent single nucleotide polymorphisms known to be associated with higher risk of caries, dentures and missing teeth at genome wide levels (p&lt;5x10 -8 ). The primary analysis employed summary statistics-based MR to assess the relationship between poor oral health and risk of ICH in any brain location. Secondary analyses evaluated deep and lobar ICH separately. Results: The primary analysis using the inverse variance-weighted MR method showed that genetically-increased risk of poor oral health was associated with a higher risk of ICH (OR 2.34, [1.08-5.06], p=0.029). Secondary analyses indicated a more potent association with deep ICH (OR 3.20 [1.34-7.6], p=0.008), whereas the link with lobar ICH was not statistically significant (OR 1.32 [0.53-3.27], p=0.543). Sensitivity analyses detected no horizontal pleiotropy in our findings (MR-PRESSO global test p-values &gt;0.05). Conclusion: Genetically-determined poor oral health is associated with an increased risk of ICH, particularly in the case of deep ICH. Because gene-disease associations are less prone to confounding, our results suggest that this association is causal. However, further analyses are needed to validate these results and identify the mediating mechanisms. Because oral health is an easily modifiable process, it may be a promising target for very early interventions focused on mitigating the risk of hemorrhagic stroke.

Abstract WMP81: Overweight Patients Had Higher Odds of Favorable Outcome After Both Deep and Lobar Intracerebral Hemorrhage

Introduction: Intracerebral Hemorrhage (ICH) leads to high rates of morbidity and mortality. Malnutrition is common in stroke patients and leads to worse outcomes. Body mass index (BMI) is a widely available marker of nutrition status, however studies on BMI and post-ICH outcomes are limited and have conflicting results. We aim to clarify this relationship by examining the relationship between BMI, nutritional lab markers, ICH severity, and functional outcome at discharge stratified by ICH location. Methods: We leveraged data from an ongoing longitudinal ICH study of adults with spontaneous primary ICH. Patients were divided into underweight, normal weight, overweight, and obese according to World Health Organization BMI criteria. Albumin, B12, total bilirubin, cholesterol, CRP, ferritin, iron, folate, hbA1c, HDL, LDL, hemoglobin, MCV, INR, ALT, triglycerides, and vitamin D were abstracted from health records. Associations between BMI, lab markers, ICH volume, and favorable outcome (mRS 0-2) were analyzed using univariate and multivariable logistic regression stratified by deep versus lobar hemorrhage location, with normal weight as the reference. Results: 1,370 patients (719 with deep hemorrhage, 651 with lobar hemorrhage) were included. There was no association between BMI and ICH volume in patients with deep or lobar hemorrhage. Multivariable analyses adjusting for age, education, diabetes mellitus, coronary artery disease, alcohol use, ICH volume, and intraventricular hemorrhage showed that overweight, but not underweight or obese, subjects had higher odds of favorable outcome on discharge in the deep (OR 3.16, 95% CI 1.36-7.34) and lobar (OR 3.15, 95% CI 1.67-5.94) groups. Albumin (OR 2.27, 95% CI 1.05-4.90) and hemoglobin (OR 1.31, 95% CI 1.09-1.59) were the only labs associated with favorable outcome in the deep hemorrhage group while no markers were associated with favorable outcome in the lobar hemorrhage group. Albumin and hemoglobin were not associated with being overweight. Conclusion: Overweight patients had three times higher odds of favorable outcome after both deep and lobar hemorrhages. This was not driven by ICH severity or explained by lab markers. Future biomarker studies are needed to better understand this relationship.