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Background and purpose Acute leukocytosis is a well-established response to intracerebral hemorrhage (ICH). Leukocytes, because of their interaction with platelets and coagulation factors, may in turn play a role in hemostasis. We investigated whether admission leukocytosis was associated with reduced bleeding following acute ICH. Methods Consecutive patients with primary ICH were prospectively collected from 1994 to 2015 and retrospectively analyzed. We included subjects with a follow-up CT scan available and automated complete white blood cell (WBC) count performed within 48 h from onset. Baseline and follow-up hematoma volumes were calculated with semi-automated software and hematoma expansion was defined as volume increase > 30% or 6 mL. The association between WBC count and ICH expansion was investigated with multivariate logistic regression. Results 1302 subjects met eligibility criteria (median age 75 years, 55.8 % males), of whom 207 (15.9 %) experienced hematoma expansion. Higher leukocyte count on admission was associated with reduced risk of hematoma expansion (Odds Ratio for 1000 cells increase [OR] 0.91, 95 % Confidence Interval [CI] 0.86–0.96, p=0.001). The risk of hematoma expansion was inversely associated with neutrophil count (OR 0.90, 95 % CI 0.85–0.96, p=0.001) and directly associated with monocyte count (OR 2.71, 95 % CI 1.08–6.83, p=0.034). There was no association between lymphocyte count and ICH expansion (OR 0.96, 95 % CI 0.79–1.17, p=0.718). Conclusions Higher admission WBC count is associated with lower risk of hematoma expansion. This highlights a potential role of the inflammatory response in modulating the coagulation cascade following acute ICH.

IMPORTANCE Hematoma expansion is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to small vessel disease (SVD), but the association between the severity of the underlying SVD and the extent of bleeding at the acute phase is unknown to date. OBJECTIVE To investigate the association between key magnetic resonance imaging (MRI) markers of SVD (as per the Standards for Reporting Vascular Changes on Neuroimaging [STRIVE] guidelines) and hematoma volume and expansion in patients with lobar or deep ICH. DESIGN, SETTING, AND PARTICIPANTS Analysis of data collected from 418 consecutive patients admitted with primary lobar or deep ICH to a single tertiary care medical center between

IMPORTANCECalcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH).OBJECTIVE To investigate whether a low serum calcium level is associated with an increase in the extent of bleeding in patients with ICH as measured by baseline hematoma volume and risk of hematoma expansion. DESIGN, SETTING, AND PARTICIPANTSProspective cohort study of 2103 consecutive patients with primary ICH ascertained during the period between 1994 and 2015 at an academic medical center. The statistical analysis was performed in January 2016. MAIN OUTCOMES AND MEASURESTotal calcium level was measured on admission, and hypocalcemia was defined as a serum calcium level of less than 8.4 mg/dL. Baseline and follow-up hematoma volumes, detected by noncontrast computed tomography, were measured using a computer-assisted semiautomatic analysis. Hematoma expansion was defined as an increase of more than 30% or 6 mL from baseline ICH volume. Associations between serum calcium level and baseline hematoma volume and between serum calcium level and ICH expansion were investigated in multivariable linear and logistic regression models, respectively. RESULTS A total of 2123 patients with primary ICH were screened, and 2103 patients met the inclusion criteria (mean [SD] age, 72.7 [12.5] years; 54.3% male patients), of whom 229 (10.9%) had hypocalcemia on admission. Hypocalcemic patients had a higher median baseline hematoma volume than did normocalcemic patients (37 mL [IQR, 15-72 mL] vs 16 mL [IQR, 6-44 mL]; P < .001). Low calcium levels were independently associated with higher baseline ICH volume (β = −0.13, SE = .03, P < .001). A total of 1393 patients underwent follow-up noncontrast computed tomography and were included in the ICH expansion analysis. In this subgroup, a higher serum calcium level was associated with reduced risk of ICH expansion (odds ratio, 0.55 [95% CI, 0.35-0.86]; P = .01), after adjusting for other confounders.CONCLUSIONS AND RELEVANCE Hypocalcemia correlates with the extent of bleeding in patients with ICH. A low calcium level may be associated with a subtle coagulopathy predisposing to increased bleeding and might therefore be a promising therapeutic target for acute ICH treatment trials.

NCT01176565.

IMPORTANCE The computed tomographic angiography (CTA) spot sign is associated with intracerebral hemorrhage (ICH) expansion and may mark those patients most likely to benefit from intensive blood pressure (BP) reduction.OBJECTIVE To investigate whether the spot sign is associated with ICH expansion across a wide range of centers and whether intensive BP reduction decreases hematoma expansion and improves outcome in patients with ICH and a spot sign. DESIGN, SETTING, AND PARTICIPANTS SCORE-IT (Spot Sign Score in Restricting ICH Growth) is a preplanned prospective observational study nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized clinical trial. Participants included consecutive patients with primary ICH who underwent a CTA within 8 hours from onset at 59 sites from May 15, 2011, through December 19, 2015. Data were analyzed for the present study from July 1 to August 31, 2016. MAIN OUTCOMES AND MEASURESPatients in ATACH-II were randomized to intensive (systolic BP target, <140 mm Hg) vs standard (systolic BP target, <180 mm Hg) BP reduction within 4.5 hours from onset. Expansion of ICH was defined as hematoma growth of greater than 33%, and an unfavorable outcome was defined as a 90-day modified Rankin Scale score of 4 or greater (range, 0-6). The association among BP reduction, ICH expansion, and outcome was investigated with multivariable logistic regression.RESULTS A total of 133 patients (83 men [62.4%] and 50 women [37.6%]; mean [SD] age, 61.9 [13.1] years) were included. Of these, 53 (39.8%) had a spot sign, and 24 of 123 without missing data (19.5%) experienced ICH expansion. The spot sign was associated with expansion with sensitivity of 0.54 (95% CI, 0.34-0.74) and specificity of 0.63 (95% CI, 0.53-0.72). After adjustment for potential confounders, intensive BP treatment was not associated with a significant reduction of ICH expansion (relative risk, 0.83; 95% CI, 0.27-2.51; P = .74) or improved outcome (relative risk of 90-day modified Rankin Scale score Ն4, 1.24; 95% CI, 0.53-2.91; P = .62) in spot sign-positive patients. CONCLUSIONS AND RELEVANCEThe predictive performance of the spot sign for ICH expansion was lower than in prior reports from single-center studies. No evidence suggested that patients with ICH and a spot sign specifically benefit from intensive BP reduction. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01176565

Background and Purpose Noncontrast CT hypodensities have been shown to be associated with hematoma expansion in intracerebral hemorrhage (ICH), but their impact on functional outcome is yet to be determined. We evaluated whether baseline noncontrast CT hypodensities are associated with poor clinical outcome. Methods We performed a retrospective review of a prospectively collected cohort of consecutive patients with primary ICH presenting to a single academic medical center between1994 and 2016. The presence of CT hypodensities was assessed by two independent raters on the baseline CT. Unfavorable outcome was defined as a modified Rankin score >3 at 90 days. The associations between CT hypodensities and unfavorable outcome were investigated using uni- and multivariable logistic regression models. Results During the study period 1342 patients presented with ICH, and 800 met restrictive inclusion criteria (baseline CT available for review, and 90 day outcome available). 304 (38%) showed hypodensities on CT, and 520 (65%) experienced unfavorable outcome. In univariate analysis, patients with unfavorable outcome were more likely to demonstrate hypodensities (48% vs 20%, p<0.0001). After adjustment for age, admission Glasgow Coma Scale, warfarin use, intraventricular hemorrhage, baseline ICH volume and location, CT hypodensities were independently associated with an increase in the odds of unfavorable outcome (OR 1.70, 95%CI [1.10 – 2.65], p=0.018). Conclusions The presence of noncontract CT hypodensities at baseline independently predicts poor outcome and comes as a useful and widely available addition to our ability to predict ICH patients’ clinical evolution.

Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed. The overall burden of small vessel disease (SVD) for CAA was calculated by a cumulative score based on CMB number, WMH severity, cSS presence and extent and CSO-PVS severity. The estimated cumulative dementia incidence at 1 year was 14% (95% confidence interval (CI): 5%-23%), and 5 years 73% (95% CI: 55%, 84%). Age (hazard ratio (HR) 1.05 per year, 95% CI: 1.01-1.08, p = 0.007), presence of MCI status (HR 3.40, 95% CI: 1.97-6.92, p < 0.001), MTA (HR 1.71 per point, 95% CI: 1.26-2.32, p = 0.001), and SVD score (HR 1.23 per point, 95% CI: 1.20-1.48, p = 0.030) at baseline were independent predictors for dementia conversion in these patients. Cognitive deterioration of CAA patients appears attributable to cumulative changes, from both vasculopathic and neurodegenerative lesions.