Computed Tomography Angiography Spot Sign Research Articles

The spot sign predicts hematoma expansion, outcome, and mortality in patients with primary intracerebral hemorrhage.

ObjectiveThe purpose of this study was to retrospectively review cases of intracerebral hemorrhage (ICH) medically treated at our institution to determine if the CT angiography (CTA) 'spot sign' predicts in-hospital mortality and clinical outcome at 3 months in patients with spontaneous ICH.MethodsWe conducted a retrospective review of all consecutive patients who were admitted to the department of neurosurgery. Clinical data of patients with ICH were collected by 2 neurosurgeons blinded to the radiological data and at the 90-day follow-up.ResultsMultivariate logistic regression analysis identified predictors of poor outcome; we found that hematoma location, spot sign, and intraventricular hemorrhage were independent predictors of poor outcome. In-hospital mortality was 57.4% (35 of 61) in the CTA spot-sign positive group versus 7.9% (10 of 126) in the CTA spot-sign negative group. In multivariate logistic analysis, we found that presence of spot sign and presence of volume expansion were independent predictors for the in-hospital mortality of ICH.ConclusionThe spot sign is a strong independent predictor of hematoma expansion, mortality, and poor clinical outcome in primary ICH. In this study, we emphasized the importance of hematoma expansion as a therapeutic target in both clinical practice and research.

Multicenter Accuracy and Interobserver Agreement of Spot Sign Identification in Acute Intracerebral Hemorrhage

Rapid, accurate, and reliable identification of the computed tomography angiography spot sign is required to identify patients with intracerebral hemorrhage for trials of acute hemostatic therapy. We sought to assess the accuracy and interobserver agreement for spot sign identification. A total of 131 neurology, emergency medicine, and neuroradiology staff and fellows underwent imaging certification for spot sign identification before enrolling patients in 3 trials targeting spot-positive intracerebral hemorrhage for hemostatic intervention (STOP-IT, SPOTLIGHT, STOP-AUST). Ten intracerebral hemorrhage cases (spot-positive/negative ratio, 1:1) were presented for evaluation of spot sign presence, number, and mimics. True spot positivity was determined by consensus of 2 experienced neuroradiologists. Diagnostic performance, agreement, and differences by training level were analyzed. Mean accuracy, sensitivity, and specificity for spot sign identification were 87%, 78%, and 96%, respectively. Overall sensitivity was lower than specificity (P<0.001) because of true spot signs incorrectly perceived as spot mimics. Interobserver agreement for spot sign presence was moderate (k=0.60). When true spots were correctly identified, 81% correctly identified the presence of single or multiple spots. Median time needed to evaluate the presence of a spot sign was 1.9 minutes (interquartile range, 1.2-3.1 minutes). Diagnostic performance, interobserver agreement, and time needed for spot sign evaluation were similar among staff physicians and fellows. Accuracy for spot identification is high with opportunity for improvement in spot interpretation sensitivity and interobserver agreement particularly through greater reliance on computed tomography angiography source data and awareness of limitations of multiplanar images. Further prospective study is needed.

Evolution of Computed Tomography Angiography Spot Sign Is Consistent With a Site of Active Hemorrhage in Acute Intracerebral Hemorrhage

CT angiography spot sign predicts hematoma expansion in patients with acute intracerebral hemorrhage (ICH). The spot sign may represent a site of active extravasation, a locus of arrested hemorrhage forming fibrin globes, or represent associated epiphenomena such as hypertensive microaneurysms. We sought to describe the evolution of spot signs over 60 seconds in acute ICH using dynamic CT angiography and determine whether they grow and diffuse into the hematoma as would be expected with active extravasation. We prospectively identified consecutive patients presenting with spontaneous ICH<6 hours from symptom onset that completed dynamic CT angiography imaging over a 60-second acquisition protocol. We determined spot positivity, quantified spot volumes, and then used repeated-measures ANOVA to assess changes in spot volume over time. We collected data on 35 patients; 13 of 35 (37%) patients were spot-positive. Spot-positive patients had larger median ICH volume compared with spot-negative patients (median 10.7 versus 49.2 mL; P=0.007). Maximal spot sign volumes ranged from 0.02 to 2.8 mL (median 0.17 mL). Spot sign volumes increased significantly with time (P<0.001) and seemed to disperse into the hematoma in all cases. Three of 13 (23%) spot-positive patients presented with 2 distinct spot signs, but the remaining patients either had only 1 spot sign or different contiguous components of an irregularly shaped spot sign. In this dynamic CT angiography study of ICH, spot signs evolve consistent with sites of active extravasation.

Computed Tomography Angiography Spot Sign Does Not Predict Case Fatality in Aneurysmal Subarachnoid Hemorrhage With Intraparenchymal Extension

Many patients with aneurysmal subarachnoid hemorrhage (SAH) with intraparenchymal extension develop early hematoma expansion, which is not explained by aneurysmal rerupture in half of cases. In patients with primary intracerebral hemorrhage, the computed tomography angiography (CTA) spot sign predicts hematoma expansion and poor outcome. We conducted a 2-center prospective cohort study to evaluate whether CTA spot sign predicts case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension. We studied consecutive patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Two experienced readers, blinded to clinical data, analyzed CTAs for spot sign presence. We assessed the proportion of patients with the CTA spot sign and tested its association with in-hospital and 90-day case fatality, using univariable and multivariable logistic regression. In 32 of 236 patients (14%), we found at least 1 spot sign. Acute surgical hematoma evacuation with aneurysm occlusion occurred in 120 patients (51%). The overall in-hospital case fatality rate was 37%. The CTA spot sign was not associated with in-hospital (multivariable odds ratio, 0.51 [95% confidence interval, 0.06-3.26]) or 90-day (multivariable odds ratio, 0.59 [0.21-1.65]) case fatality. The found frequency of CTA spot signs is lower after aneurysmal than primary intracerebral hemorrhage and is not associated with in-hospital or 90-day case fatality in patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension.

Abstract TMP84: A Prediction Score for Hematoma Expansion Following Acute Intracerebral Hemorrhage

Purpose: Hematoma expansion (HE) following acute intracerebral hemorrhage (ICH) is common and associated with poor outcome. Ongoing clinical trials therefore focus on restricting HE. In order to provide treatment options to the patients at highest risk of HE, we aimed to develop a prediction score for HE. Methods: We performed a prospective cohort study of consecutive primary ICH patients presenting to a single center over a 12-year period, with available baseline and follow-up CTs. HE was assessed using semi-automated software and defined as 6 mL or 33% growth. Our cohort was randomly divided in a 2/3 development and 1/3 validation cohort. Uni- and multivariate logistic regression was performed to assess clinical and neuroimaging covariates for relationship with HE. A prediction model was derived based on regression estimates, and this model was subsequently tested in the validation cohort. Results: 817 ICH patients were included: 544 in the development cohort and 273 in the validation cohort. Overall, HE occurred in 156 patients (19%). In multivariate analysis, warfarin use (OR 2.09 [95%CI 1.24-3.52], p = 0.006), shorter time to CT (≤6 vs. &gt;6 hours; OR 2.14 [95%CI 1.18-3.90], p = 0.013), baseline ICH volume (&lt;30, 30-60, &gt;60 mL; OR 1.90 [95%CI 1.01-3.55], p = 0.045), and the CT angiography spot sign (OR 3.59 [95%CI 1.77-7.29], p = 0.0004) were predictive of HE. The derived prediction score (0-9) showed a linear relation with the probability of HE and mortality (at discharge and 90 days), in both the development and the validation cohorts. The probability of HE in the validation cohort was 0%, 10%, 39%, and 54% for categorized scores 0, 1-3, 4-6, and 7-9, respectively. The c statistics were 0.69 for the development cohort and 0.78 for the validation cohort. Conclusion: Warfarin use, presentation within 6 hours after ICH, larger ICH volumes at baseline, and the CT angiography spot sign are independent predictors of HE and mortality. Based on these findings, we developed a prediction score for HE. Since no therapy has demonstrated benefit in a randomized trial, our results open a path for individualized treatment and trial design in ICH, aimed at patients at highest risk of HE.

Abstract WMP83: Prediction of Intracerebral Hematoma Expansion: Multicenter External Validation of the CTA Spot Sign Score

Background and Purpose: The spot sign score (SSS) stratifies hematoma expansion risk in patients with acute intracerebral hemorrhage (ICH) but is not externally validated. We sought to validate the SSS and assess prognostic spot characteristics associated with hematoma expansion in a prospective multicenter study. Methods: We studied 228 ICH patients presenting &lt; 6 hours post-onset enrolled in the PREDICT (PREdicting hematoma growth anD outcome in ICH using contrast bolus CT) study, a multicentre prospective observational cohort study of ICH patients evaluated with baseline non-contrast CT, CT angiography (CTA), and 24-hour follow-up CT. Primary outcome was significant hematoma expansion (&gt;6ml or &gt;33%). Secondary outcomes were absolute and relative expansion. Blinded CTA spot sign characterization (spot number, maximum axial size and attenuation, and relative attenuation compared to the ipsilateral internal carotid artery and superior sagittal sinus) and SSS calculation was performed independently by two neuroradiologists and a radiology resident. Multivariable regression for prediction of hematoma expansion was performed and diagnostic performance of the SSS and spot characteristics was examined with ROC analysis and tests for trend. Results: SSS independently predicted significant, absolute, and relative hematoma expansion (p-values of 0.001, &lt;0.001, and 0.009, respectively), adjusting for initial hematoma volume, INR, mean arterial pressure, and time from onset-to-baseline CT, and demonstrated near perfect interobserver agreement (κ = 0.82). Spot number and SSS demonstrated similar area under the curve (AUC 0.69 vs. 0.68, p=0.149) for hematoma expansion. Incremental risk of hematoma expansion was demonstrated with increasing SSS however a significant trend was not identified (p trend=0.720). Of all spot characteristics, only spot number was independently associated with expansion (p&lt;0.001) providing incremental risk stratification (p trend=0.050) and near perfect agreement (κ=0.85). Median absolute hematoma growth for 0, 1, 2 to 3, ≥4 spots was 0.4, 4, 12, 82 ml respectively. Conclusion: Spot number is the single best predictor of significant ICH expansion and appears to be as good as the total SSS in predicting expansion.

Abstract WP294: CT Angiography Spot Sign Predicts Perioperative Bleeding in Primary Intracerebral Hemorrhage

Purpose: While hematoma evacuation for intracerebral hemorrhage (ICH) showed no clinical benefit in one large randomized trial, meta-analyses have suggested an effect for certain subgroups. Knowledge of which patients will be found to show active bleeding may help guide surgical treatment. The spot sign, i.e. contrast extravasation following CT angiography (CTA), is thought to represent active bleeding. We therefore investigated whether spot sign presence predicts active bleeding during surgery for ICH. Methods: Consecutive primary ICH patients who underwent a CTA followed by surgical hematoma evacuation were included over a 10-year period. CTAs were reviewed for spot sign presence by an experienced reader, blinded to clinical and surgical data. Active bleeding and re-bleeding following surgery were assessed using 5-point rating scales. The association between the spot sign and active perioperative bleeding, postoperative re-bleeding, and postoperative change in hematoma volume was evaluated using univariate and multivariate logistic regression. Results: During the study period, 1082 ICH patients presented to our institution, of whom 75 met inclusion criteria. 34 (45%) were lobar, 13 (17%) deep, 26 (35%) cerebellar, 1 (1%) brainstem, and 1 (1%) primary intraventricular hemorrhage. At least one spot sign was identified in 29 patients (39%). In multivariate analysis, spot sign was the sole predictor of active bleeding during surgery (OR 2.86 [95%CI 1.05-8.17], p = 0.044). Presence of spot sign (OR 4.46 [95%CI 1.24-18.17], p = 0.027) and female sex (OR 6.71 [95%CI 1.79-33.28], p = 0.009) were predictive of re-bleeding and larger postoperative ICH volumes. A trend toward significance was found for the association of re-bleeding with both discharge mortality ( p = 0.055) and 90-day mortality ( p = 0.073). Conclusion: This is the first study to show that CTA spot sign marks ongoing bleeding in patients undergoing hematoma evacuation following acute ICH. Patients with this finding suffer more perioperative bleeding, more postoperative re-bleeding, and larger residual ICH volumes. Our results may contribute to the selection of which ICH patients may benefit from surgery.

Abstract 114: The Predictive Ability of the CTA Spot Sign for Hematoma Expansion is Dependent on Time Since ICH Onset: A Systematic Review and Patient-level Meta-analysis.

Background: Hematoma expansion (HE) occurs in up to 40% of patients with intracerebral hemorrhage (ICH), and predicts poor clinical outcome. Contrast extravasation following CT-angiography (CTA), termed “spot sign”, identifies patients at highest risk of HE. However, the prevalence and predictive values of the spot sign varies across studies, possibly due to differences in onset-to-CTA time. We therefore performed a patient-level meta-analysis to define the relationship between onset-to-CTA time and the prevalence &amp; predictive value of spot sign, and the size of HE. Methods: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Library Database of Systematic Reviews, MEDLINE and EMBASE for studies of CTA spot sign prevalence and HE. We pooled data on the prevalence and predictive values for significant HE (defined as either 6mL or 33% growth of ICH) for patients with ICH stratified by onset-to-CTA time: &lt;3hours, 3-6 hours, &gt;6hours. We used chi-square analysis to assess the spot sign in each time strata, and two-way ANOVA to compare across time strata. Results: We identified ICH spot sign databases derived from 7 countries and 14 centers (n=705). Prevalence of spot sign decreased with increasing onset-to-CTA time (Table; p&lt;0.001). The subset with follow-up scans used for HE analysis (n=582) revealed spot sign sensitivity and PPV were highest in the earliest time strata, whereas specificity and NPV were highest in the latest time strata (Table). Spot positive patients had greatest absolute HE in the earlier CTA time strata (median spot positive growth 6.8mL, 5.6mL, 5.2mL for 6hr respectively; p&lt;0.001; means in Table). Conclusion: Prevalence, predictive values and magnitude of effect of the spot sign are dependent on onset-to-CTA timing; these results are relevant to both ICH trial design and acute management.

Clinical Applications of the Computed Tomography Angiography Spot Sign in Acute Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (ICH) is the most fatal form of stroke, with 1-month morality rates often exceeding 40% and rates of death or severe disability exceeding 75%.1,2 Nearly 20 years ago, the first observational studies demonstrated that hematoma volume on presentation was among the most potent predictors of survival and functional outcome.3 Subsequent studies identified the frequent occurrence of hematoma expansion after the initial computed tomography (CT) scan.4 Occurring in ≤40% of patients, this expansion further contributes to poor outcome.5,6 These observations have made the arrest of expansion the most common target for acute clinical trials in ICH.7–9 Thus far, the specific targeting of hematoma expansion in clinical trials has yet to yield improvement in clinical outcome. This may be attributed to difficulty in identifying those individuals most likely to benefit from the intervention, those who will experience hematoma expansion. Risk factors for expansion include early presentation, baseline hematoma volume, and warfarin use.4,10,11 Even among patients presenting within 3 hours, however, expansion severe enough to cause clinical deterioration occurs in no more than 40%.4,6–8 The CT angiography (CTA) spot sign has emerged in recent years as a potent predictor of hematoma expansion, and a potential tool in guiding therapies in both research and clinical care. ### Definition First described in 1999,12 the CTA spot sign has evolved in its definition from the broader concept of contrast extravasation, comprising high-density material or contrast leakage within the hematoma,12–14 to encompass foci of enhancement within the hematoma on CTA source images.15 Although definitions of the spot sign used in individual studies continue to vary, all are variations on this standard (Table 1). In 2009, a spot sign score was …

CTA Spot Sign Predicts Hematoma Expansion in Patients with Delayed Presentation After Intracerebral Hemorrhage

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. 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. 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. 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.

Stroke: Highlights of Selected Articles

<i>Stroke:</i> Highlights of Selected Articles

Apolipoprotein E Genotype Is Associated With CT Angiography Spot Sign in Lobar Intracerebral Hemorrhage

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. 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. 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. 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.

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study

In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion. PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis. We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47–73) for the positive predictive value and 78% (71–84) for the negative predictive value, with 51% (39–63) sensitivity and 85% (78–90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002). These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH. Canadian Stroke Consortium and NovoNordisk Canada.

Abstract 104: APOE Genotype Is Associated With CT Angiography Spot Sign In Lobar Intracerebral Hemorrhage

Purpose: The presence of active contrast extravasation following CT angiography (CTA), the spot sign, predicts the development of hematoma expansion and poor clinical outcome in patients with primary intracerebral hemorrhage (ICH). The biological underpinnings of the spot sign remain poorly understood, and there are no established risk factors for its presence. We conducted a prospective cohort study to identify determinants of the CTA spot sign. Materials and Methods: We performed a prospective cohort study of consecutive patients presenting to a single center with primary ICH over an 11-year period. Patients were included in this analysis if they underwent CT and CTA at presentation and consented to participation in genetic studies. CTAs were reviewed by two experienced readers, blinded to clinical data, according to previously published validated criteria. Due to its established association with lobar ICH volume, APOE genotype, as well as common clinical covariates, were analyzed for association with spot sign presence. Analyses were stratified by deep, lobar and probable / definite cerebral amyloid angiopathy (CAA) related ICH (by Boston criteria). Results: Of 372 patients, 151 had deep, 198 had lobar and 23 had mixed ICH. We identified at least 1 spot sign in 96 of 372 patients (25.8%). 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, p-value 0.013) in deep ICH, OR 2.86 (95% CI 1.33-6.13, p-value 0.007) in lobar ICH and OR 6.65 (95% CI 1.34-32.99, p-value 0.020) in the subset meeting criteria for CAA-related ICH. APOE ε2, but not ε4, was associated with spot sign in lobar ICH (OR 2.09 [95% CI 1.05-4.19], p = 0.036) and CAA-related ICH (OR 2.07 [95% CI 1.24-3.46], p-value 0.005). There was no effect for ε2 or ε4 in deep ICH. ( Table 1 ) Conclusion: Patients on warfarin at the time of ICH are more likely to have a spot sign at presentation, regardless of the location of the ICH. Among patients with lobar ICH, those who possess the APOE ε2 allele are more likely to have a spot sign. Given the established relationship between APOE ε2 and vasculopathic changes in CAA, our findings suggest that both hemostatic factors and vessel pathology influence spot sign presence and risk of prolonged bleeding in ICH.

Intracerebral hemorrhage: toward physiological imaging of hemorrhage risk in acute and chronic bleeding.

Despite improvements in management and prevention of intracerebral hemorrhage (ICH), there has been little improvement in mortality over the last 30 years. Hematoma expansion, primarily during the first few hours is highly predictive of neurological deterioration, poor functional outcome, and mortality. For each 10% increase in ICH size, there is a 5% increase in mortality and an additional 16% chance of poorer functional outcome. As such, both the identification and prevention of hematoma expansion are attractive therapeutic targets in ICH. Previous studies suggest that contrast extravasation seen on CT Angiography (CTA), MRI, and digital subtraction angiography correlates with hematoma growth, indicating ongoing bleeding. Contrast extravasation on the arterial phase of a CTA has been coined the CTA Spot Sign. These easily identifiable foci of contrast enhancement have been identified as independent predictors of hematoma growth, mortality, and clinical outcome in primary ICH. The Spot Sign score, developed to stratify risk of hematoma expansion, has shown high inter-observer agreement. Post-contrast leakage or delayed CTA Spot Sign, on post contrast CT following CTA or delayed CTA respectively are seen in an additional ∼8% of patients and explain apparently false negative observations on early CTA imaging in patients subsequently undergoing hematoma expansion. CT perfusion provides an opportunity to acquire dynamic imaging and has been shown to quantify rates of contrast extravasation. Intravenous recombinant factor VIIa (rFVIIa) within 4 h of ICH onset has been shown to significantly reduce hematoma growth. However, clinical efficacy has yet to be proven. There is compelling evidence that cerebral amyloid angiopathy (CAA) may precede the radiographic evidence of vascular disease and as such contribute to microbleeding. The interplay between microbleeding, CAA, CTA Spot Sign and genetic composition (ApoE genotype) may be crucial in developing a risk model for ICH.

CT angiography spot sign predicts in-hospital mortality in patients with secondary intracerebral hemorrhage

Background and objectiveThe presence of active contrast extravasation during CT angiography, the spot sign, is a potent predictor of in-hospital mortality in patients with primary intracerebral hemorrhage (ICH). However, its...

Spotlight on the July 26 Issue

#### Notable in Neurology This issue features an article that investigates the association of ultraearly hematoma growth with the CT angiography spot sign, hematoma expansion, and clinical outcomes in patients with acute intracerebral hemorrhage and another that investigates tau pathology in Alzheimer disease and mild cognitive impairment using PET. A featured article presents formal consensus-based guidance for the management of myasthenia gravis. ### Advanced interatrial block and ischemic stroke: The Atherosclerosis Risk in Communities Study The authors examine the association between advanced interatrial block and ischemic stroke in 14,716 participants followed for 22 years using a time-to-event analysis. Their findings suggest that advanced interatrial block, a marker of atrial fibrosis and abnormal cardiac remodeling of …

The Spot Sign Is More Common in the Absence of Multiple Prior Microbleeds

Mural thickening and permeability changes in patients with amyloid angiopathy (CAA) and chronic hypertension are implicated in the pathophysiology of multiple, chronic subclinical microbleeds. The Spot sign, contrast extravasation on CT angiography, predicts hematoma expansion and is presumed to represent acute vessel damage. We hypothesize that the Spot sign is more common in patients without multiple prior chronic microbleeds. A retrospective study was conducted of 59 patients presenting within 6 hours of primary intracranial hemorrhage onset undergoing CT angiography and MRI. CT angiography spot sign presence was documented blinded to MRI. Hematoma expansion was defined as >6 mL or 30% enlargement. The Boston criteria were applied to microbleed interpretation dichotomizing subjects into probable and negative CAA. Basal ganglia, thalamic, and brain stem microbleed location were interpreted as chronic hypertensive pattern. Univariate logistic regression and ordinal logistic regression analysis identified significant predictive factors between spot-positive and -negative patients or microbleed pattern. The incidence of spot positivity was 42%, 22%, and 0% for CAA-negative, chronic hypertensive, and CAA-positive patients, respectively (P=0.01). CAA-negative patients had higher baseline National Institutes of Health Stroke Scale (P=0.039), larger follow-up hematoma volume (P=0.02), and poorer Rankin score (P=0.049) than chronic hypertensive or CAA-positive patients. After age adjustment, spot-positive (P=0.023), age-related white matter change (P=0.041), number of microbleeds (P<0.0001), and modified Rankin score (P=0.027) remained significantly different between groups. Boston criteria-defined CAA-negative status demonstrates the highest risk of spot positivity compared with patients with probable CAA and chronic hypertension.

Systematic characterization of the computed tomography angiography spot sign in primary intracerebral hemorrhage identifies patients at highest risk for hematoma expansion: the spot sign score.

The presence of active contrast extravasation (the spot sign) on computed tomography (CT) angiography has been recognized as a predictor of hematoma expansion in patients with intracerebral hemorrhage. We aim to systematically characterize the spot sign to identify features that are most predictive of hematoma expansion and construct a spot sign scoring system. We retrospectively reviewed CT angiograms performed in all patients who presented to our emergency department over a 9-year period with primary intracerebral hemorrhage and had a follow-up noncontrast head CT within 48 hours of the baseline CT angiogram. Three neuroradiologists reviewed the CT angiograms and determined the presence and characteristics of spot signs according to strict radiological criteria. Baseline and follow-up intracerebral hemorrhage volumes were determined by computer-assisted volumetric analysis. We identified spot signs in 71 of 367 CT angiograms (19%), 6 of which were delayed spot signs (8%). The presence of any spot sign increased the risk of significant hematoma expansion (69%, OR=92, P<0.0001). Among the spot sign characteristics examined, the presence of > or =3 spot signs, a maximum axial dimension > or =5 mm, and maximum attenuation > or =180 Hounsfield units were independent predictors of significant hematoma expansion, and these were subsequently used to construct the spot sign score. In multivariate analysis, the spot sign score was the strongest predictor of significant hematoma expansion, independent of time from ictus to CT angiogram evaluation. The spot sign score predicts significant hematoma expansion in primary intracerebral hemorrhage. If validated in other data sets, it could be used to select patients for early hemostatic therapy.

Acute Stroke Triage to Intravenous Thrombolysis and Other Therapies with Advanced CT or MR Imaging: Pro CT

Max Wintermark, MD Howard A. Rowley, MD Michael H. Lev, MD A s outlined by Kohrmann and Schellinger in their pro magnetic resonance (MR) imaging article, the two primary goals of acute stroke imaging are to distinguish ischemic stroke from intracranial hemorrhage (ICH) and to select ischemic stroke patients for reperfusion therapies. In this article, we too will focus on ischemic stroke imaging. Although our focus remains on nonhemorrhagic stroke with respect to the advantages of advanced computed tomography (CT) over advanced MR imaging in stroke evaluation in all comers, we wish to underscore that CT angiography is becoming increasingly important in the evaluation of patients with ICH, as it has the ability to depict underlying vascular malformations, such as aneurysms, that could warrant immediate surgery. Moreover, the detection of active contrast material extravasation at CT angiography (the recently described spot sign) also has predictive value with regard to both hematoma growth (1,2) and mortality (3). This spot sign has the potential, in future clinical trials, to be used to select patients with ICH who are eligible for factor VIIa therapy. To our knowledge, there is no MR counterpart for the CT angiography spot sign. Also, MR studies can be difficult to perform in patients with ICH, as they are often critically ill and require mechanical support and intensive monitoring; furthermore, there is a need for extremely rapid assessment and triage, given the potential risks of herniation, intracranial hypertension, and death. CT remains an available, affordable, and— for stroke triage—accurate modality.