Search

Introduction: Oral Anticoagulation Therapy (OAT) resumption after ICH is a dilemma due to increased risk of recurrent ICH, particularly after lobar ICH caused by underlying Cerebral Amyloid Angiopathy (CAA). Apolipoprotein E ( APOE ) ε2/ε4 alleles are risk factors for recurrent CAA-related ICH. Hypothesis: APOE genotype predicts lobar ICH recurrence after OAT-ICH. Methods: We enrolled survivors of lobar OAT-ICH in a prospective single-center study to determine whether APOE ε2/ε4: 1) are associated with ICH recurrence following OAT-ICH, using time-to-event analyses; 2) improved prediction of ICH recurrence when added to MRI-based CAA markers (cerebral microbleeds [CMBs], white matter hyperintensities [WMH], expanded peri-vascular spaces [EPVS], and cortical superficial siderosis [CSS]), using Harrell’s C-statistic; 3) could be incorporated in a classification scheme to predict ICH recurrence, as defined by recursive partitioning analysis (RPA). Results: We followed 110 lobar OAT-ICH survivors for a median time of 52.2 months (IQR: 33.5-61.7). We observed 26 recurrent ICH events, corresponding to an annual recurrence rate of 5.7%. APOE ε2/ε4 variants were associated with ICH recurrence following OAT-ICH (ε2: HR 2.14, 95% CI 1.20-3.82; ε4: HR 1.50, 95% CI 1.21-3.47). These associations remained significant after adjusting for anticoagulation status, antiplatelet use, CMBs, WMH, EPVS, and CSS. Inclusion of APOE genotype alongside MRI data resulted in improved predictive ability for ICH recurrence (Harrell’s C: 0.76 vs. 0.68, p=0.034). RPA revealed that APOE ε2/ε4 stratified likelihood of ICH recurrence among otherwise low risk individuals based on MRI data alone (Figure). Conclusions: APOE genotype predicts lCH recurrence following lobar OAT-ICH, and improves predictive performance when added to established neuroimaging markers. APOE-based lobar ICH recurrence prediction warrants further investigation and may affect clinical practice.

Introduction: Perihematomal edema (PHE) expansion rate may be an independent predictor of poor functional outcome following spontaneous intracerebral hemorrhage (ICH). We examined whether this association varies by ICH location. Hypothesis: The effect size of PHE expansion rate on mortality and poor functional outcome will be greater for deep ICH compared to lobar ICH. Methods: Subjects (n=139) were retrospectively identified from a prospective ICH cohort enrolled from 2000-2013. Inclusion criteria: ≥18 years of age, spontaneous supratentorial ICH, and known time of onset. Exclusion criteria: infratentorial or primary intraventricular hemorrhage, subsequent surgery, trauma, or warfarin-related ICH. ICH, PHE, and intraventricular hemorrhage (IVH) volumes were measured from CT scans. PHE expansion rates were calculated from serial PHE volume measurements. Logistic regression assessed the association between PHE expansion rate and mortality or poor functional outcome (modified Rankin Scale >2) at 90 days. Odds ratios are per 0.04 mL/h. Results: PHE expansion rate from baseline to 24 hours (PHE24) predicts mortality for deep (p=0.03, OR 1.13[1.02-1.26]) and lobar ICH (p=0.02, OR 1.03[1.00-1.06]) in unadjusted regression, and in models adjusted for age (Deep: p=0.02; Lobar: p=0.03), blood pressure (Deep: p=0.02; Lobar: p=0.04), IVH volume (Deep: p=0.02; Lobar: p=0.05), Glasgow Coma Scale (Deep: p=0.03; Lobar: p=0.02), or time to baseline CT (Deep: p=0.05; Lobar: p=0.05). PHE24 also predicts mortality for lobar ICH adjusting for ICH volume (p=0.05, OR 1.03[1-1.06]). A significant interaction exists between ICH location and PHE expansion rate from baseline to 72 hours (PHE72) in models predicting mRS>2 (p=0.04). PHE72 predicts mRS>2 for deep but not lobar ICH (p-values not shown) in models that are unadjusted (p=0.02, OR 4.04[1.25-13.04]) or adjusted for ICH volume (p=0.02, OR 4.3[1.25-14.98]), age (p=0.03, OR 5.4[1.21-24.11]), blood pressure (p=0.05, OR 3.28[1.02-10.57]), IVH volume (p=0.02, OR 4.59[1.28-16.41]), GCS (p=0.02, OR 4.19[1.2-14.55]), or time to first CT (p=0.03, OR 4.02[1.19-13.56]). Conclusion: PHE72 predicts poor functional outcomes exclusively after deep ICH, whereas PHE24 predicts mortality for deep and lobar ICH.

Background and Purpose: There have been conflicting reports regarding the association between peri-hematomal edema (PHE) in spontaneous intracerebral hemorrhage (ICH) and outcome. We hypothesized that PHE expansion rate from baseline to 24 hours predicts mortality and poor functional outcome after ICH. Methods: ICH, PHE and intraventricular hemorrhage volumes were measured for 139 subjects who presented with primary ICH and received head computed tomography scans at baseline and 24-hours post-ICH. Subjects were retrospectively identified from a prospective cohort study of ICH. Inclusion criteria were age over 18 years with primary spontaneous supratentorial ICH. Exclusion criteria were infratentorial hemorrhage, primary intraventricular hemorrhage, or any suspected cause of secondary ICH. Logistic regression was performed to evaluate the relationship between PHE expansion rate and 90-day mortality and functional outcome. Poor functional outcome was defined as a modified Rankin Scale (mRS) score > 2. Results: There was a strong association between PHE expansion rate and mortality (OR 1.42, p = 0.0025) and a trend in the correlation between PHE expansion rate and poor outcome (OR 1.50, p = 0.07). In a multivariable model accounting for hematoma volume and time from symptom onset to 24 hour scan, PHE expansion rate was a significant predictor of mortality (OR 1.07, p = 0.032). In a multivariable model accounting for hematoma volume, age, Glasgow Coma Scale score, presence of intraventricular hemorrhage and time from symptom onset to 24 hour scan, PHE expansion rate predicted poor functional outcome (OR 2.58, p = 0.05). Conclusions: PHE expansion rate predicts outcome in ICH and may represent a novel therapeutic target.