Severe Intracerebral Hemorrhage Research Articles

Clinical usefulness of Edinburgh CT criteria in patients with lobar intracerebral hemorrhage

Identifying the cause of intracerebral hemorrhage (ICH) is relevant to optimize its management. We aimed to assess the applicability and utility of the Edinburgh CT criteria for cerebral amyloid angiopathy (CAA) in an unselected cohort of hospitalized patients. We retrospectively applied the Edinburgh criteria to the first available brain CTs of patients hospitalized for a first-ever lobar ICH in the district of L'Aquila from 2011 to 2017. ICH characteristics and outcomes were compared according to the presence of the Edinburgh CT criteria, including associated subarachnoid hemorrhage (aSAH) and finger-like projections (FLPs). The outcome of ICH in-hospital mortality was assessed with multivariate logistic regression analysis. We adopted the Edinburgh criteria, age, NIHSS and Glasgow Coma Scale scores, systolic blood pressure, antiplatelet treatment, ICH volume, and intraventricular extension on admission as covariates. Of 178 patients with lobar ICH, 52 (29.2%) had aSAH+FLPs, 60 (33.7%) aSAH only, 1 (0.6%) FLPs, and 65 (36.5%) none. Patients with aSAH+FLPs were older (79.0 ± 9.2 years) than those with only one criterion or none (74.0 ± 15.3 and 72.2 ± 13.8 years, respectively; P = 0.020). Patients with aSAH+FLPs also had more severe ICH at onset, higher in-hospital case-fatality (log rank test P = 0.003) and higher mRS scores at discharge (P < 0.001) as compared to those fulfilling one or none of the Edinburgh criteria. Low Glasgow Coma Scale score was the only factor independently associated to in-hospital case-fatality (odds ratio per point increase 0.51; 95% confidence interval, 0.32-0.91; P = 0.021). Our data suggest the applicability of the Edinburgh CT criteria in a hospital setting. The presence of those criteria reflects ICH clinical severity. Applying the Edinburgh CT criteria might help refining the diagnosis and improving the management of patients with lobar ICH.

Clinical value of perilesional perfusion deficit measured by Technetium-99m-ECD single-photon emission computed tomography in hypertensive intracerebral hemorrhage.

Pathological and experimental studies indicate the existence of a “penumbra” of progressive tissue damage and edema in regions immediately surrounding a hematoma in patients of intracerebral hemorrhage (ICH). This zone of oligemia surrounding ICH has a potential for perfusion recovery. Improved understanding of the pathophysiology of perilesional blood flow changes and brain injury after ICH may result in improved treatment strategies. The aim was to study perilesional blood flow changes in ICH by perfusion deficit (PD) measured by single-photon emission computed tomography (SPECT) and to correlate it with the severity of ICH and outcome. Forty-four patients of computed tomography (CT) documented nonlobar deep ICH suggestive of hypertensive hematoma of <7 days duration were subjected to 99mTc-ethylene diacetate SPECT scans of the brain. Patients with significant midline shift (0.5 cm) or global blood flow reduction were excluded from the analysis. SPECT scan of the brain was analyzed by segmental analysis, a semi-quantitative method of cerebral blood flow. A difference of radiotracer uptake of >10% between the region of interest of ICH cases and the ratio between the two ROI below 0.9 was taken as a significant PD. A correlation of PD was analyzed with that of various parameters such as the severity of stroke, duration from onset of ictus, and imaging including CT scan of the brain and SPECT scan. A statistically significant difference in the percentage of radiotracer uptake on comparison of ipsilateral and contralateral to ICH (P < 0.001) was observed, suggesting a significant hypoperfusion in the perilesional area in patients with ICH. A statistically significant correlation was noted between the severity of stroke and PD indicated by various parameters such as the National Institutes of Health Stroke Scale (NIHSS) score at admission (r = 0.328, P = 0.016), Glasgow Coma Scale (GCS) score at admission (r = −0.388, P = 0.005), and ICH score at admission (r = 0.314, P = 0.020). This study demonstrated more severe hypoperfusion in clinically severe ICH which is a possible explanation of poor outcomes in severe ICH cases. We observed hypoperfusion on SPECT study in 25 of 34 (73.5%) patients with subacute ICH and 5 of 10 patients (50%) with acute ICH. The mean time from the onset of ictus to SPECT scan done was 5.04 ± 1.75 days with a range of 1–7 days, suggesting the persistence of hypoperfusion in subacute stages too. This finding may be of clinical importance for identifying the salvageable area surrounding ICH for any possible intervention in future to improve the outcome. This study demonstrates that perilesional PD occurs in acute and subacute cases of ICH. This hypoperfusion is possibly time related and appears to be more severe in patients having major ICH with poor clinical and imaging parameters. This area of hypoperfusion or ischemic penumbra is a potential site for perfusion recovery to improve clinical outcomes and to reduce long-term neurological deficits.

Intensive Blood Pressure Lowering in Patients with Moderate to Severe Grade Acute Cerebral Hemorrhage: Post Hoc Analysis of Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 Trial

Objective: To study the effect of intensive blood pressure reduction in patients with moderate to severe intracerebral hemorrhage (ICH) within the subjects recruited in Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. Design: Randomized, multicenter, 2 group, open-label clinical trial. Setting: A total of 110 sites in the USA, Japan, China, Taiwan, South Korea, and Germany. Patients: A total of 1,000 patients underwent randomization from May 2011 till September 2015. Interventions: We analyzed the effect of intensive (goal 110–139 mm Hg) over standard (goal 140–179 mm Hg) systolic blood pressure (SBP) reduction using intravenous nicardipine within 4.5 h of symptom onset in moderate to severe grade subjects with ICH in a non-prespecified analysis. Moderate to severe grade was defined by Glasgow Coma Scale score <13 or baseline National Institutes of Health Stroke Scale score ≥10 or baseline intraparenchymal hemorrhage volume ≥30 mL or presence of intraventricular hemorrhage. The primary outcome was death or disability (score 4–6 on the modified Rankin scale) at 3 months after randomization ascertained by a blinded investigator. Measurements and Main Results: Of a total of 682 subjects who met the definition of moderate to severe grade (mean age 61.9 ± 13.1 years, 62.5% men) with a mean baseline SBP of 174.7 ± 24.8 mm Hg, the frequency of hematoma expansion was significantly lower among subjects randomized to intensive SBP reduction than among subjects randomized to standard SBP reduction (20.4 vs. 27.9%, relative risk [RR]: 0.7; 95% confidence interval [CI]: 0.55–0.96). The primary endpoint of death or disability was observed in 52.5% (170/324) of subjects receiving intensive SBP reduction and 48.9% (163/333) of subjects receiving standard SBP reduction (RR: 1.1; 95% CI: 0.9–1.2). Conclusions: Intensive SBP lowering reduced the frequency of hematoma expansion but did not reduce the rate of death or disability in patients with moderate to severe grade ICH.

Surrogate Satisfaction with Decision Making After Intracerebral Hemorrhage.

Surrogate decision makers for patients with intracerebral hemorrhage (ICH) are frequently asked to make difficult decisions on use of life-sustaining treatments. We explored ICH surrogate satisfaction with decision making and experience of decision regret using validated measures in a prospective multicenter study. Cases of non-traumatic ICH were enrolled from three hospitals (September 2015-December 2016), and surrogate decision makers were invited to complete a self-administered survey. The primary outcome was the 10-item decision-making subscale of the Family Satisfaction in the Intensive Care Unit scale (FSICU-DM, range 0-100, higher is greater satisfaction), and the secondary outcome was the decision regret scale (range 0-100, higher is greater regret). Linear regression models were used to assess the association between satisfaction with decision making and pre-specified covariates using manual backward selection. A total of 73 surrogates were approached for participation (in person or mail), with 48 surrogates returning a completed survey (median surrogate age 60.5years, 63% female, 77% white). Patients had a median age of 72.5, 54% were female, with a median admission Glasgow coma scale of 10, in-hospital mortality of 31%, and 56% with an in-hospital DNR order. Physicians commonly made treatment recommendation (> 50%) regarding brain surgery or transitions to comfort measures, but rarely made recommendations (< 20%) regarding DNR orders. Surrogate satisfaction with decision making was generally high (median FSICU-DM 85, IQR 57.5-95). Factors associated with higher satisfaction on multivariable analysis included greater use of shared decision making (P < 0.0001), younger patient age (p = 0.02), ICH score of 3 or higher (p = 0.03), and surrogate relationship (spouse vs. other, p = 0.02). Timing of DNR orders was not associated with satisfaction (P > 0.25). Decision regret scores were generally low (median 12.5, IQR 0-31.3). Considering the severity and abruptness of ICH, it is reassuring that surrogate satisfaction with decision making was generally high and regret was generally low. However, more work is needed to define the appropriate outcome measures and optimal methods of recruitment for studies of surrogate decision makers of ICH patients.

The association between plasma HMGB1 and sRAGE and clinical outcome in intracerebral hemorrhage

High-mobility group box 1 (HMGB1) and advanced glycation end-products (RAGE) are potential mediators of inflammation. We investigate the association between levels of HMGB1 and soluble RAGE (sRAGE) following intracerebral hemorrhage (ICH) and the severity of ICH. There was a significant trend towards higher poor functional outcome rate with increasing HMGB1 and sRAGE tercile. The correlation analysis indicated that the levels of HMGB1and sRAGE were positively correlated with hematoma volume. The receiver operating curve (ROC) was 0.718 for HMGB1 and 0.631 for sRAGE to poor functional outcome. HMGB1 and sRAGE quantification provides more accurate prognostic information after ICH.

Serum netrin-1 concentrations are associated with clinical outcome in acute intracerebral hemorrhage

BackgroundNetrin-1 is an axon guidance protein, which can inhibit inflammatory reaction and stabilize the blood-brain barrier to protect against experimental brain injury. We evaluated the concentration of netrin-1 in acute intracerebral hemorrhage (ICH) patients and explored whether netrin-1 is a potential prognostic biomarker for ICH. MethodsThis study recruited a total of 126 ICH patients and 126 healthy controls. Netrin-1 concentration was determined using a commercially available human enzyme-linked immune sorbent assay kit. National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used to assess hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. ResultsICH patients showed significantly lower serum netrin-1 concentrations than controls. Serum netrin-1 concentrations were strongly and inversely correlated with serum C-reactive protein concentrations, NIHSS score and hematoma volume. Multivariate analyses revealed that low netrin-1 concentration was associated with 90-day death, unfavorable outcome and overall survival after adjustment for other confounding variables. Under the receiver operating characteristic curve, serum netrin-1 remarkably discriminated patients at risk of 90-day death and unfavorable outcome. ConclusionsSerum netrin-1 concentrations are decreased in patients with ICH, and the concentrations of netrin-1 were intimately associated with inflammation, hemorrhagic severity and clinical outcome of ICH.

Serum substance P levels and early mortality of spontaneous intracerebral haemorrhage patients

Introduction and goalSubstance P, a neuropeptide of the tachykinin family, is involved in the neuroinflammation of different diseases of the central nervous system. To our knowledge, there is no published data on the level of circulating substance P levels in the prognosis of patients with spontaneous intracerebral hemorrhage (ICH). Therefore, the objectives of this observational and prospective study were to determine whether serum substance P levels in ICH patients were associated with early mortality and whether could be used in the mortality prognostic. Material and methodsWe included patients with severe primary supratentorial ICH (defined as Glasgow Coma Scale < 9) from 6 Intensive Care Units of Spanish hospitals. We determined serum substance P levels at the time of severe ICH diagnosis, at fourth and at eighth day. Thirty-day mortality was considered the end-point study. FindingsNon-surviving (n=53) compared to surviving ICH patients (n=64) showed higher serum substance P levels at day 1 (p<0.001), day 4 (p<0.001) and day 8 (p<0.001). The area under the curve for 30-day mortality prediction by serum substance P levels was of 79% (95% CI = 70–86%; p<0.001). Kaplan–Meier analysis showed a higher 30-day mortality in patients with serum substance P levels>503 pg/mL (Hazard ratio=14.7; 95% CI=6.88–31.55; p<0.001). Multiple logistic regression analysis showed an association between serum substance P levels and 30-day mortality (Odds Ratio=1.006; 95% CI=1.002–1.010; p=0.004) controlling for ICH score, midline shift, glycemia, early evacuation of ICH. ConclusionsThus, the novel aspects our study include that serum substance P levels in severe primary ICH patients were higher in non-surviving than in surviving patients, that serum substance P levels were associated with early mortality controlling for other variables, and that serum substance P levels could be used as biomarkers of prognosis.

Intravenous Human Umbilical Cord-Derived Mesenchymal Stromal Cell Administration in Models of Moderate and Severe Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggest mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared with other disorders such as ischemic stroke. Herein, we employed a model of collagenase-induced ICH in young adult rats to investigate the potential therapeutic effects of an intravenous injection of human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs). Two doses of collagenase were used to cause moderate or severe hemorrhages. Magnetic resonance imaging showed that animals treated with hUC-MSCs after moderate ICH had smaller residual hematoma volumes than vehicle-treated rats, whereas the cell therapy failed to decrease the hematoma volume in animals with a severe ICH. Functional assessments (rotarod and elevated body swing tests) were performed for up to 21 days after ICH. Enduring neurological impairments were seen only in animals subjected to severe ICH, but the cell therapy did not induce statistically significant improvements in the functional recovery. The biodistribution of Technetium-99m-labeled hUC-MSCs was also evaluated, showing that most cells were found in organs such as the spleen and lungs 24 h after transplantation. Nevertheless, it was possible to detect a weak signal in the brain, which was higher in the ipsilateral hemisphere of rats subjected to a severe ICH. These data indicate that hUC-MSCs have moderately beneficial effects in cases of less severe brain hemorrhages in rats by decreasing the residual hematoma volume, and that optimization of the therapy is still necessary.

Abstract TP353: Long-term Outcomes in Patients With Intracerebral Hemorrhage and Delayed Hospital Presentation

Background: Delays in medical care are known to be associated with worse outcomes in ischemic stroke, but outcomes in patients with intracerebral hemorrhage (ICH) and delayed presentation are unclear. We aimed to determine factors associated with prolonged delays from ICH symptom onset to hospital presentation and implications for long-term outcomes. Methods: We performed a single-center cohort study using data from consecutive ICH patients over 12 months. ICH characteristics and outcomes were prospectively collected, while time of symptom onset (or last-known-well) and emergency department arrival were retrospectively abstracted. We calculated time-to-arrival and defined prolonged delay as &gt;24 hours. Using multivariable logistic regression, we determined factors associated with prolonged delays to presentation, then determined associations with unfavorable 3-month outcomes (modified Rankin Scale [mRS] 4-6) after adjusting for demographics and ICH severity. Results: Of 299 patients with out-of-hospital ICH, 21% (n=62) presented &gt;24 hours from symptom onset; median time-to-arrival was 5.5 hours (IQR 1.2-17.8). There were not significant differences in age (mean 71.9±14.0 vs. 70.4±16.0, p=0.50), sex (48% vs. 50% male, p=0.80), race (89% vs. 82% white, p=0.22), or ICH size (mean 15.5±23.2 vs. 20.5±27.4cc, p=0.19) between patients presenting &gt;24 hours and &lt;24 hours from symptom onset, though patients with prolonged delays were less likely to have initial GCS &lt;13 (16% vs. 34%, p=0.02) and therefore had modestly lower ICH scores (median 1 [0-2] vs. 1 [1-2], p=0.02). Patients with prolonged delays had lower 3-month mRS scores than patients who presented earlier (median 3 [1.5-4] vs. 4 [3-6], p=0.002), and lower odds of unfavorable 3-month outcome in adjusted models (OR 0.46, 95% CI 0.22-0.97). Conclusions: Outcomes in ICH patients with prolonged delays to presentation differ from those who present earlier. ICH severity in such patients may not be accurately captured by established predictors, and prognostication models should therefore account for inherent survivorship bias.

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 TMP19: MRI Characteristics and Predictors of Diffusion Weighted Hyperintense Lesions After Spontaneous Intracerebral Hemorrhage: A Secondary Analysis of MISTIE-III

Introduction: Mechanisms of diffusion weighted hyperintense lesions (DWIHL) after spontaneous intracerebral hemorrhage (ICH) are controversial. We evaluated mechanism and outcome of DWIHL. Methods: Protocolized MRI scans within 7 days from ICH were reviewed from MISTIE-III trial. Imaging analysis included DWIHL, leukoariosis (Fazekas score), enlarged perivascular space (EPVS), and cerebral microbleeds. Multivariable logistic regression analysis was performed to assess predictors and outcomes of having DWIHLs. Favorable outcome was defined as modified Rankin Score 0-3 at 12 months. Results: Of 499 patients, 300 underwent DWI studies (62% lobar ICH; 38% deep ICH) and 178 (59%) had acute DWIHLs (66% lobar; 34% deep). DWIHL locations were perihematomal in 140 (79%); and remote in 96 (54%). In multivariable regression analysis, DWIHLs were associated with initial mean arterial pressure [MAP] (odds ratio [OR]: 1.004; 95% confidence interval [CI]: 1.002-1.01), initial ICH volume (OR: 1.004; 95%CI: 1.001-1.01), NIHSS at randomization (OR: 1.01; 95%CI: 1.01-1.02), hypertension history (OR: 1.41; 95%CI: 1.04-1.93), and Fazekas score (OR: 1.04; 95%CI: 1.01-1.08). Patients with DWIHLs were less likely to have favorable outcome (66% vs. 50%; OR: 0.89; 95%CI: 0.81-0.99) after adjusting for ICH severity; however, the presence of DWIHLs did not confer an independent mortality risk at 12 months. In addition, perihematomal DWIHLs were associated with ICH volume (OR: 1.003; 95%CI: 1.00-1.01), NIHSS (OR: 1.01; 95%CI: 1.00-1.02), deep location (OR: 1.25; 95%CI: 1.10-1.42), and centrum semiovale EPVS score (OR: 0.99; 95% CI: 0.99-1.00). Remote DWIHLs were associated with Fazekas score (OR: 1.17; 95%CI: 1.06-1.29), centrum semiovale EPVS score (OR: 1.01; 95%CI: 1.00-1.01), atrial fibrillation (OR: 1.40; 95%CI: 1.04-1.90), and maximal ΔMAP on first 24 hours (OR: 1.004; 95%CI: 1.001-1.006). Conclusions: DWIHLs were common (59%) in patients after spontaneous ICH, predominantly in lobar locations and were associated with unfavorable neurologic outcome. While perihematomal DWIHLs were associated with ICH severity, remote DWIHLs suggested different mechanisms including acute blood pressure reduction, cardiac emboli, and white matter disease severity.

Abstract TMP92: Serum Markers of Physiologic Stress and Associations With Delirium in Patients With Intracerebral Hemorrhage

Background: Delirium occurs frequently in patients with intracerebral hemorrhage (ICH), though its pathogenesis may be multifactorial. Given the potential role of systemic stressors in delirium, we aimed to explore differences in commonly measured markers of physiologic stress between delirious and non-delirious ICH patients. Methods: We performed a single-center cohort study using data from consecutive non-comatose ICH patients over 12 months. ICH and patient characteristics were prospectively collected, and the presence of delirium at any point during hospitalization was diagnosed based on DSM-5 criteria. We retrospectively abstracted admission laboratory values and selected three common markers of physiologic stress for comparison: neutrophil-lymphocyte ratio (NLR), troponin, and glucose. Using multivariable models adjusted for demographics, relevant comorbidities, and ICH severity, we determined associations between delirium and the following: NLR, using linear regression; elevated troponin (&gt;0.05 ng/mL), using binary logistic regression; and elevated glucose (categorized as 130-180 or &gt;180 mg/dL), using ordered logistic regression. Results: Of 284 ICH patients in our cohort, 55% (n=157) had delirium. Patients with delirium were not significantly older than non-delirious patients (mean age 71.7±16.2 vs. 68.3±15.1, p=0.07), but had larger ICH volumes (mean 23.3±24.6 vs. 7.0±10.6 cc, p&lt;0.001) and were more likely to have intraventricular hemorrhage (55% vs. 22%, p&lt;0.001). Delirious patients also had higher admission NLR (mean 9.0±10.4 vs. 6.4±5.5, p=0.01) and glucose (mean 146.5±59.6 vs. 129.9±41.4 mg/dL, p=0.008), and were more likely to have elevated troponin (21% vs. 10%, p=0.02). In adjusted models, patients with delirium had higher admission NLR than patients who were never delirious (adjusted mean difference 2.6, 95% CI 0.3-4.9), and were more likely to have elevated admission troponin (OR 2.8, 95% CI 1.2-6.4) and glucose (OR 2.0, 95% CI 1.1-3.6). Conclusions: Delirium after ICH is independently associated with elevated serum markers of physiologic stress, suggesting that systemic factors may be implicated in delirium pathogenesis.

Abstract 18: Diffusion Weighted Imaging Lesions in Patients With Acute Intracerebral Hemorrhage: A Pooled Analysis of Individual Patient Data From MISTIE-III, ATACH-II, I-DEF, and ERICH

Introduction: The etiology and significance of diffusion weighted imaging (DWI) lesions in patients with acute intracerebral hemorrhage (ICH) remain unclear. We evaluated which factors were associated with DWI lesions, whether associated factors differed by ICH location, and whether DWI lesions were associated with functional outcomes. Methods: We pooled individual patient data from the MISTIE III trial, the ATACH-II trial, the i-DEF trial, and the ERICH study. We included only patients who underwent protocolized magnetic resonance imaging (MRI) of the brain. A poor functional outcome was defined as a modified Rankin Scale (mRS) score of 4-6 at 3-6 months. We used mixed effects logistic regression with the study database as a random effect. Results: Among 1,775 ICH patients, there were 621 (35.6%) lobar, 978 (55.9%) deep, and 148 (8.5%) infratentorial ICHs. Median time to MRI scan was 1.5 days (IQR, 1-4). DWIHLs occurred in 559 (31.5%) patients, with 190 (34.3%) in lobar ICH and 320 (57.8%) in deep ICHs. In mixed effects regression models, factors associated with DWIHLs included younger age factors associated with DWIHLs after acute ICH included younger age (OR, 0.98; 95% CI, 0.97-0.99), black race (OR, 1.59; 95% CI, 1.18-2.16), admission systolic blood pressure (SBP per 10 mm Hg, OR, 1.13; 95% CI, 1.05-1.22), cerebral microbleeds (OR, 1.71, 95% CI, 1.24-2.35), and leukoaraiosis (OR, 1.60; 95% CI, 1.14-2.25). Patients with DWIHLs had higher odds of mRS 4-6 (OR, 1.57; 95% CI, 1.24-1.99) compared to those without, after adjustment for demographics and ICH severity. In subgroup analyses, similar factors influenced DWIHLs in deep ICH. However, in lobar ICH, younger age, admission SBP, and leukoaraiosis were associated with DWIHLs. Presence of DWIHLs was independently associated with poor mRS in deep ICH but not in lobar ICH. There was no relationship between acute BP lowering and DWIHLs, regardless of location. Conclusions: In a large, heterogeneous cohort of ICH patients, our results are consistent with the hypothesis that DWIHLs represent the effects of chronic hypertensive vasculopathy and acute blood pressure elevation. Furthermore, DWIHLs portend poor prognosis after ICH, particularly in deep hemorrhages.

Mortality in patients with intracerebral hemorrhage associated with antiplatelet agents, oral anticoagulants or no antithrombotic therapy

The association between preceding treatment with antiplatelet agents (APs), vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) and mortality after intracerebral hemorrhage (ICH) remains unclear.The aim of this multicenter, prospective cohort study was to assess the risk for death after ICH in consecutive patients who were on treatment with APs, VKAs, DOACs, or no antithrombotic agent. The primary outcome was in-hospital death by day 30. ICH volume at admission and volume expansion were centrally assessed.Out of 598 study patients, in-hospital death occurred in 21% of patients who were on treatment with APs, 25% with VKAs, 30% with DOACs, and 13% with no antithrombotics. Crude death rate was higher in patients on antithrombotics as compared to patients receiving no antithrombotic agent. At multivariate analysis, age (HR 1.07; 95% CI 1.04–1.10), previous stroke (HR 1.83; 95% CI 1.14–2.93), GCS ≤8 at admission (HR 6.06; 95% CI 3.16–9.74) and GCS 9–12 (HR 3.38; 95% CI 1.81–6.33) were independent predictors of death. Treatment with APs (HR 1.29; 95% CI 0.61–2.76), VKAs (HR 1.42; 95% CI 0.70–2.88) or DOACs (HR 1.28; 95% CI 0.61–2.73) were not predictors of death in the overall study population, in non-trauma associated ICH as well as when GCS was not included in the model. ICH volume and volume expansion were independent predictors of death.In conclusion, preceding treatment with antithrombotic is associated with the severity of ICH. Age, previous stroke and clinical severity at presentation were independent predictors of in-hospital death in patients with ICH.

Associations of Radiographic Cerebral Small Vessel Disease with Acute Intracerebral Hemorrhage Volume, Hematoma Expansion, and Intraventricular Hemorrhage

Background and ObjectiveThe aim of this study was to evaluate the impact of radiographic cerebral small vessel disease (CSVD) on the severity of acute intracerebral hemorrhage (ICH) as measured by: ICH volume, hematoma expansion, and extension of intraventricular hemorrhage (IVH).MethodsCSVD was determined on baseline computed tomography (CT) scans of patients from the Ethnic and Racial Variations of Intracerebral Hemorrhage study through the extent of leukoaraiosis and cerebral atrophy using visual rating scales. The associations of leukoaraiosis and atrophy with ICH volume, hematoma expansion, IVH presence, and severity of IVH were tested using multivariable regression models. Secondary analyses were stratified by hemorrhage location. Bonferroni correction was applied to correct for multiple testing.ResultsA total of 2579 patients (mean age 61.7 years, 59% male) met inclusion criteria. Median ICH volume was 10.5 (Interquartile range [IQR] 4.0–25.3) mL. IVH was detected in 971 patients (38%). Neither leukoaraiosis nor atrophy was associated with hematoma expansion. Increasing grades of leukoaraiosis were associated with increased risk of IVH in a dose-dependent manner, while cerebral atrophy was inversely associated with IVH (both P for trend < 0.001). Increasing grades of global atrophy were dose-dependently associated with lower ICH volumes (ß (95% Confidence Interval [CI]) − 0.30[− 0.46, − 0.14], − 0.33[− 0.49, − 0.17], − 0.40[− 0.60, − 0.20], and − 0.54[− 0.76, − 0.32], for grades 1, 2, 3 and 4 compared to 0; all P < 0.001). The associations of leukoaraiosis with ICH volume were consistent with those of atrophy, albeit not meeting statistical significance.ConclusionsLeukoaraiosis and cerebral atrophy appear to have opposing associations with ICH severity. Cerebral atrophy correlates with smaller ICH volume and decreased risk and severity of IVH, while leukoaraiosis is associated with increased risk of IVH. Whether these observations reflect overlapping or divergent underlying mechanisms requires further study.

Evaluation of Serum Ferritin as a Prognostic Marker in Acute Hemorrhagic Stroke.

Background Acute hemorrhagic stroke (AHS) resulting from intracerebral hemorrhage (ICH) is a rampant neurological disorder with devastating consequences, particularly in Indians. Recently, serum ferritin levels have been related to adverse cardiovascular and stroke outcomes. We aimed to evaluate the prognostic utility of serum ferritin in AHS. Materials and Methods Admission serum ferritin levels were estimated in 50 AHS patients with primary supratentorial hemorrhage. Study subjects were categorized based on their prognostic scores in modified Rankin scale (mRS) assessment. Ferritin levels were compared across the study groups, correlated with mRS and other ICH severity indicators. Results Serum ferritin and other ICH severity indices such as Glasgow coma scale (GCS) and ICH volume were significantly altered in the mRS groups by the end of 7th and 30th days of hospitalization. Elevated ferritin levels, ICH volume together with decreased GCS, characterized the groups with adverse prognosis. Serum ferritin moderately correlated with GCS ( r = –0.643), ICH volume ( r = 0.562), and had significantly higher correlations with long-term prognostic scores of 7th day mRS ( r = 0.802) and 30th day mRS ( r = 0.916). Conclusion Elevated admission serum ferritin levels indicate poor AHS short-term and long-term outcomes, thereby making serum ferritin a possible prognostic index for the same.

High Serum DNA and RNA Oxidative Damage in Non-surviving Patients with Spontaneous Intracerebral Hemorrhage.

One study found higher leukocytes 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in patients with spontaneous intracerebral hemorrhage (ICH) than in healthy subjects due to the oxidation of guanosine from deoxyribonucleic acid (DNA). The objective of this study was to determine whether there is an association between oxidative damage of serum DNA and ribonucleic acid (RNA) and mortality in patients with ICH. In this observational and prospective study, patients with severe supratentorial ICH (defined as Glasgow Coma Scale < 9) were included from six Intensive Care Units of Spanish hospitals. At the time of severe ICH diagnosis, concentrations in serum of malondialdehyde (as lipid peroxidation biomarker) and of the three oxidized guanine species (OGS) (8-hydroxyguanosine from RNA, 8-hydroxyguanine from DNA or RNA, and 8-OHdG from DNA) were determined. Thirty-day mortality was considered the end-point study. Serum levels of OGS (p < 0.001) and malondialdehyde (p = 0.002) were higher in non-surviving (n = 46) than in surviving patients (n = 54). There was an association of serum OGS levels with serum malondialdehyde levels (rho = 0.36; p = 0.001) and 30-day mortality (OR = 1.568; 95% CI 1.183-2.078; p = 0.002). The novel and most important finding of our study was that serum OGS levels in ICH patients are associated with mortality.

Increased perihematomal neuron autophagy and plasma thrombin-antithrombin levels in patients with intracerebral hemorrhage: An observational study.

Animal studies have demonstrated that autophagy was involved in neuronal damage after intracerebral hemorrhage (ICH). Several studies showed thrombin–antithrombin (TAT) plasma levels were elevated in patients with ICH. In this study, we aimed to evaluate if autophagy occurred in patients with ICH; and the relationship between the severity of brain injury and plasma TAT levels.A novel tissue harvesting device was used during hematoma removal surgery to collect loose fragments of tissue surrounding the affected brain area in 27 ICH patients with hematoma volumes of >30 mL in the basal ganglia. Control tissues were obtained from patients who underwent surgery for arteriovenous malformation (n = 25). Transmission electron microscopy (TEM) and immunohistochemistry for autophagy-related proteins were used to evaluate the ultrastructural and morphologic cellular characteristics; and the extent of autophagy in the recovered tissue specimens. Stroke severity was assessed by using the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma TAT levels.Transmission electron microscopy showed autophagosomes and autolysosomes exist in neurons surrounding the hematoma, but not in the control tissues. The number of cells containing autophagic vacuoles correlated with the severity of brain injury. Immunohistochemistry showed strong LC3, beclin 1, and cathepsin D staining in ICH tissue specimens. Plasma TAT levels correlated positively with autophagic cells and ICH severity (P < .01).Autophagy was induced in perihematomal neurons after ICH. Autophagy and plasma TAT levels correlated positively with severity of brain injury. These results suggest that autophagy and increased plasma TAT levels may contribute to the secondary damage in ICH patients.

Intracranial Hypertension and Cerebral Perfusion Pressure Insults in Adult Hypertensive Intraventricular Hemorrhage: Occurrence and Associations With Outcome.

Elevated intracranial pressure and inadequate cerebral perfusion pressure may contribute to poor outcomes in hypertensive intraventricular hemorrhage. We characterized the occurrence of elevated intracranial pressure and low cerebral perfusion pressure in obstructive intraventricular hemorrhage requiring extraventricular drainage. Prospective observational cohort. ICUs of 73 academic hospitals. Four hundred ninety-nine patients enrolled in the CLEAR III trial, a multicenter, randomized study to determine if extraventricular drainage plus intraventricular alteplase improved outcome versus extraventricular drainage plus saline. Intracranial pressure and cerebral perfusion pressure were recorded every 4 hours, analyzed over a range of thresholds, as single readings or spans (≥ 2) of readings after adjustment for intracerebral hemorrhage severity. Impact on 30- and 180-days modified Rankin Scale scores was assessed, and receiver operating curves were analyzed to identify optimal thresholds. Of 21,954 intracranial pressure readings, median interquartile range 12 mm Hg (8-16), 9.7% were greater than 20 mm Hg and 1.8% were greater than 30 mm Hg. Proportion of intracranial pressure readings from greater than 18 to greater than 30 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 70 mm Hg were associated with day-30 mortality and partially mitigated by intraventricular alteplase. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and intracranial pressure greater than 20 mm Hg in spans were associated with both 30-day mortality and 180-day mortality. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 60 mm Hg were associated with poor day-30 modified Rankin Scale, whereas cerebral perfusion pressure less than 65 and less than 75 mm Hg were associated with poor day-180 modified Rankin Scale. Elevated intracranial pressure and inadequate cerebral perfusion pressure are not infrequent during extraventricular drainage for severe intraventricular hemorrhage, and level and duration predict higher short-term mortality and long-term mortality. Burden of low cerebral perfusion pressure was also associated with poor short- and long-term outcomes and may be more significant than intracranial pressure. Adverse consequences of intracranial pressure-time burden and cerebral perfusion pressure-time burden should be tested prospectively as potential thresholds for therapeutic intervention.

Systemic inflammatory response syndrome and long-term outcome after intracerebral hemorrhage.

ObjectiveTo investigate whether the systemic inflammatory response syndrome (SIRS) without infection as surrogate of a systemic immune response is associated with poor long-term functional outcome in patients with spontaneous intracerebral hemorrhage (ICH).MethodsWe analyzed consecutive patients with spontaneous ICH from our prospective cohort study (2018–2015). SIRS was defined according to standard criteria: i.e., 2 or more of the following parameters during hospitalization: body temperature <36°C or >38°C, respiratory rate >20 per minute, heart rate >90 per minute, or white blood cell count <4,000/μL or >12,000/μL in the absence of infection. The primary outcome consisted of the modified Rankin Scale (mRS) at 3 and 12 months investigated by adjusted ordinal shift analyses. Bias and confounding were addressed by propensity score matching and multivariable regression models.ResultsOf 780 patients with ICH, 21.8% (n = 170) developed SIRS during hospitalization. Patients with SIRS showed more severe ICH compared with those without; i.e., larger ICH volumes (18.3 cm3, interquartile range [IQR 4.6–47.2 cm3] vs 7.4 cm3, IQR [2.4–18.6 cm3]; p < 0.01), increased intraventricular hemorrhage (57.6%, n = 98/170 vs 24.8%, n = 79/319; p < 0.01), and poorer neurologic admission status (NIH Stroke Scale score 16, IQR [7–30] vs 6, IQR [3–12]; p < 0.01). ICH severity-adjusted analyses revealed an independent association of SIRS with poorer functional outcome after 3 (OR 1.80, 95% CI [1.08–3.00]; p = 0.025) and 12 months (OR 1.76, 95% CI [1.04–2.96]; p = 0.034). Increased ICH volumes on follow-up imaging (OR 1.38, 95% CI [1.01–1.89]; p = 0.05) and previous liver dysfunction (OR 3.01, 95% CI [1.03–10.19]; p = 0.04) were associated with SIRS.ConclusionsIn patients with ICH, we identified SIRS to be predictive of poorer long-term functional outcome over the entire range of mRS estimates. Clinically relevant associations with SIRS were documented for previous liver dysfunction and hematoma enlargement.