Risk factors for computed tomography angiography spot sign in deep and lobar intracerebral hemorrhage are shared.

BACKGROUND AND PURPOSE: Patients with intracerebral hemorrhage (ICH) who present with a spot sign on computed tomography angiography are at increased risk of hematoma expansion and poor outcome. Because primary ICH is the acute manifestation of chronic cerebral small vessel disease, we investigated whether different clinical or imaging characteristics predict spot sign presence, using ICH location as a surrogate for arteriolosclerosis- and cerebral amyloid angiopathy-related ICH. METHODS: Patients with primary ICH and available computed tomography angiography at presentation were included. Predictors of spot sign were assessed using uni- and multivariable regression, stratified by ICH location. RESULTS: Seven hundred forty-one patients were eligible, 335 (45%) deep and 406 (55%) lobar ICH. At least one spot sign was present in 76 (23%) deep and 102 (25%) lobar ICH patients. In multivariable regression, warfarin (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.01-5.71; P=0.04), baseline ICH volume (OR, 1.20; 95% CI, 1.09-1.33, per 10 mL increase; P<0.001), and time from symptom onset to computed tomography angiography (OR, 0.89; 95% CI, 0.80-0.96, per hour; P=0.009) were associated with the spot sign in deep ICH. Predictors of spot sign in lobar ICH were warfarin (OR, 3.95; 95% CI, 1.87-8.51; P<0.001) and baseline ICH volume (OR, 1.20; 95% CI, 1.10-1.31, per 10 mL increase; P<0.001). CONCLUSIONS: The most potent associations with spot sign are shared between deep and lobar ICH, suggesting that the acute bleeding process that arises in the setting of different chronic small vessel diseases shares commonalities.

Apolipoprotein E genotype is associated with CT angiography spot sign in lobar intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The CT angiography (CTA) spot sign predicts hematoma expansion and poor outcome in patients with primary intracerebral hemorrhage (ICH). The biological underpinnings of the spot sign remain poorly understood; it may be that the underlying vasculopathy influences its presence. Therefore, we conducted a study to identify genetic predictors of the spot sign. METHODS: In an ongoing prospective cohort study, we analyzed 371 patients with CTA and genetic data available. CTAs were reviewed for the spot sign by 2 experienced readers, blinded to clinical data, according to validated criteria. Analyses were stratified by ICH location. RESULTS: In multivariate analysis, patients on warfarin were more likely to have a spot sign regardless of ICH location (OR, 3.85; 95% CI, 1.33-11.13 in deep ICH and OR, 2.86; 95% CI, 1.33-6.13 in lobar ICH). Apolipoprotein E ε2, but not ε4, was associated with the presence of a spot sign in lobar ICH (OR, 2.09; 95% CI, 1.05-4.19). There was no effect for ε2 or ε4 in deep ICH. CONCLUSIONS: Patients with ICH on warfarin are more likely to present with a spot sign regardless of ICH location. Among patients with lobar ICH, those who possess the apolipoprotein E ε2 allele are more likely to have a spot sign. Given the established relationship between apolipoprotein E ε2 and vasculopathic changes in cerebral amyloid angiopathy, our findings suggest that both hemostatic factors and vessel pathology influence spot sign presence.

Confounding by indication in retrospective studies of intracerebral hemorrhage: antiepileptic treatment and mortality.

INTRODUCTION: Intracerebral hemorrhage (ICH) is a highly fatal disease with few proven treatments. Data to guide clinician decisions for therapies, including antiepileptic drugs (AED), are limited. Published studies on AED treatment in ICH have provided conflicting results. We investigated the effect of AED treatment on 90-day mortality after ICH in a large prospectively ascertained cohort. METHODS: We conducted a retrospective analysis of a prospectively assembled cohort of patients with ICH in the supratentorial regions, comparing 90-day mortality and modified Rankin Score among 543 patients treated with AED during hospitalization and 639 AED-free ICH. Supratentorial ICH location was categorized as lobar or deep hemispheric. RESULTS: Multivariate analysis demonstrated an association between AED treatment and reduced 90-day mortality in supratentorial ICH (OR = 0.62, 95 % CI 0.42-0.90, p = 0.01) and the subset of lobar ICH (OR = 0.49, 95 % CI 0.25-0.96, p = 0.04). When analyses were restricted to subjects surviving longer than 5 days from ICH, however, no association between AED treatment and a 90-day outcome, regardless of hemorrhage location (all p > 0.15), was detected, despite more than adequate power to detect the originally observed association. CONCLUSION: These results suggest that AED treatment in acute ICH is not associated with 90-day mortality or outcome and that any detected association could arise by confounding by indication, in which the most severely affected patients are those in whom AEDs are prescribed. They provide a cautionary example of the limitations of drawing conclusions about treatment effects from observational data.

CTA spot sign predicts hematoma expansion in patients with delayed presentation after intracerebral hemorrhage.

BACKGROUND: Hematoma expansion after acute intracerebral hemorrhage occurs most frequently in patients presenting within 3 h of symptom onset. However, the majority of patients present outside this window or with an unknown onset time. We investigated the prevalence of hematoma expansion in these patients and assessed the accuracy of the CT angiography (CTA) spot sign for identifying risk of hematoma expansion. METHODS: We analyzed 391 consecutive patients undergoing CTA and a followup CT. CTA spot sign readings were performed by two experienced readers and hematoma expansion was assessed by means of semi-automated software. RESULTS: Hematoma expansion occurred in 18 % of patients. When stratified by time from symptom onset to initial CT, hematoma expansion rates were: 39 % within 3 h; 11 % between 3 and 6 h, 11 % beyond 6 h (but with known onset), and 20 % in patients with unknown symptom onset. Of patients who developed hematoma expansion, only 38 % presented within 3 h. The accuracy of the spot sign in predicting hematoma expansion was 0.67 for patients presenting within 3 h, 0.83 between 3 and 6 h, 0.88 after 6 h, and 0.76 for patients presenting with an unknown onset time. CONCLUSIONS: A substantial number of patients destined to suffer from hematoma expansion present either late or with an unknown symptom onset time. The CTA spot sign accurately identifies patients destined to expand regardless of time from symptom onset, and may therefore open a path to offer clinical trials and novel therapies to the many patients who do not present acutely.

CT angiography spot sign in intracerebral hemorrhage predicts active bleeding during surgery.

OBJECTIVE: To determine whether the CT angiography (CTA) spot sign marks bleeding complications during and after surgery for spontaneous intracerebral hemorrhage (ICH). METHODS: In a 2-center study of consecutive spontaneous ICH patients who underwent CTA followed by surgical hematoma evacuation, 2 experienced readers (blinded to clinical and surgical data) reviewed CTAs for spot sign presence. Blinded raters assessed active intraoperative and postoperative bleeding. The association between spot sign and active intraoperative bleeding, postoperative rebleeding, and residual ICH volumes was evaluated using univariable and multivariable logistic regression. RESULTS: A total of 95 patients met inclusion criteria: 44 lobar, 17 deep, 33 cerebellar, and 1 brainstem ICH; ≥1 spot sign was identified in 32 patients (34%). The spot sign was the only independent marker of active bleeding during surgery (odds ratio [OR] 3.4; 95% confidence interval [CI] 1.3-9.0). Spot sign (OR 4.1; 95% CI 1.1-17), female sex (OR 6.9; 95% CI 1.7-37), and antiplatelet use (OR 4.6; 95% CI 1.2-21) were predictive of postoperative rebleeding. Larger residual hematomas and postoperative rebleeding were associated with higher discharge case fatality (OR 3.4; 95% CI 1.1-11) and a trend toward increased case fatality at 3 months (OR 2.9; 95% CI 0.9-8.8). CONCLUSIONS: The CTA spot sign is associated with more intraoperative bleeding, more postoperative rebleeding, and larger residual ICH volumes in patients undergoing hematoma evacuation for spontaneous ICH. The spot sign may therefore be useful to select patients for future surgical trials.

Predicting hematoma expansion after primary intracerebral hemorrhage.

IMPORTANCE: Many clinical trials focus on restricting hematoma expansion following acute intracerebral hemorrhage (ICH), but selecting those patients at highest risk of hematoma expansion is challenging. OBJECTIVE: To develop a prediction score for hematoma expansion in patients with primary ICH. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study at 2 urban academic medical centers among patients having primary ICH with available baseline and follow-up computed tomography for volumetric analysis (817 patients in the development cohort and 195 patients in the independent validation cohort). MAIN OUTCOMES AND MEASURES: Hematoma expansion was assessed using semiautomated software and was defined as more than 6 mL or 33% growth. Covariates were tested for association with hematoma expansion using univariate and multivariable logistic regression. A 9-point prediction score was derived based on the regression estimates and was subsequently tested in the independent validation cohort. RESULTS: Hematoma expansion occurred in 156 patients (19.1%). In multivariable analysis, predictors of expansion were as follows: warfarin sodium use, the computed tomography angiography spot sign, and shorter time to computed tomography (≤ 6 vs >6 hours) (P < .001 for all), as well as baseline ICH volume (<30 [reference], 30-60 [P = .03], and >60 [P = .005] mL). The incidence of hematoma expansion steadily increased with higher scores. In the independent validation cohort (n = 195), our prediction score performed well and showed strong association with hematoma expansion (odds ratio, 4.59; P < .001 for a high vs low score). The C statistics for the score were 0.72 for the development cohort and 0.77 for the independent validation cohort. CONCLUSIONS AND RELEVANCE: A 9-point prediction score for hematoma expansion was developed and independently validated. The results open a path for individualized treatment and trial design in ICH aimed at patients at highest risk of hematoma expansion with maximum potential for therapeutic benefit.