Computed Tomographic Blend Sign Is Associated With Computed Tomographic Angiography Spot Sign and Predicts Secondary Neurological Deterioration After Intracerebral Hemorrhage
Background and Purpose—Significant early hematoma growth in patients with intracerebral hemorrhage is an independent predictor of poor functional outcome. Recently, the novel blend sign (BS) has been introduced as a new imaging sign for predicting hematoma growth in noncontrast computed tomography. Another parameter predicting increasing hematoma size is the well-established spot sign (SS) visible in computed tomographic angiography. We, therefore, aimed to clarify the association between established SS and novel BS and their values predicting a secondary neurological deterioration.
Methods—Retrospective study inclusion criteria were (1) spontaneous intracerebral hemorrhage confirmed on noncontrast computed tomography and (2) noncontrast computed tomography and computed tomographic angiography performed on admission within 6 hours after onset of symptoms. We defined a binary outcome (secondary neurological deterioration versus no secondary deterioration). As secondary neurological deterioration, we defined (1) early hemicraniectomy under standardized criteria or (2) secondary decrease of Glasgow Coma Scale of >3 points, both within the first 48 hours after symptom onset.
Results—Of 182 patients with spontaneous intracerebral hemorrhage, 37 (20.3%) presented with BS and 39 (21.4%) with SS. Of the 81 patients with secondary deterioration, 31 (38.3%) had BS and SS on admission. Multivariable logistic regression analysis identified hematoma volume (odds ratio, 1.07 per mL; P≤0.001), intraventricular hemorrhage (odds ratio, 3.08; P=0.008), and the presence of BS (odds ratio, 11.47; P≤0.001) as independent predictors of neurological deterioration.
Conclusions—The BS, which is obtainable in noncontrast computed tomography, shows a high correlation with the computed tomographic angiography SS and is a reliable predictor of secondary neurological deterioration after spontaneous intracerebral hemorrhage.
Significant early hematoma growth in patients with intracerebral hemorrhage (ICH) occurs in approximately one third of the cases.1 Hematoma growth is in line with initial hematoma volume and hematoma location an independent predictor of poor functional outcome,2–5 but in contrast to them, it is potentially modifiable if detected early enough.
Recently, the novel blend sign (BS) for predicting hematoma growth in noncontrast computed tomography (NCCT) has been introduced as a highly specific new imaging sign.6 Another parameter predicting increasing hematoma size is the well-established spot sign (SS) visible in computed tomographic angiography (CTA).7,8 The major advantage of the BS is the visibility in NCCT which offers a greater availability in clinical routine and a much faster and cheaper assessment. In addition, allergic reactions to contrast medium and renal dysfunction present possible contraindications for contrast application.
We, therefore, conducted a research that aimed to clarify the association between established SS and novel BS and their values predicting a secondary neurological deterioration.
We retrospectively studied our database for patients with ICH aged >18 years between January 2010 and August 2015. As inclusion criteria, we defined (1) spontaneous ICH confirmed on NCCT and (2) NCCT and CTA performed on admission within 6 hours after onset of symptoms. Patients were excluded if they had head trauma, brain tumor, or secondary ICH from hemorrhagic transformation of ischemic infarction. As secondary neurological deterioration, we defined (1) early hemicraniectomy within the first 48 hours after symptom onset under standardized criteria according to our in-house guidelines or (2) secondary decrease of Glasgow Come Scale of >3 points within the first 48 hours. In addition, we obtained vascular risk factors (hypertension and diabetes mellitus) from patients’ clinical records.
The study was approved by the Ethics Committee of the University Muenster and the Westfalian Chamber of Physicians, Muenster, Germany. All study protocols and procedures were conducted in accordance with the Declaration of Helsinki.
The computed tomography (CT) scans were performed using standard clinical parameters with axial 5-mm section thickness. The images were obtained and stored for further evaluation. The location of the hematoma was assessed and documented. The hemorrhage locations were classified as basal ganglia, lobe, brain stem, and cerebellum. Two experienced readers independently evaluated first the presence of BS in all patients’ NCCT and after a week the presence of SS in the corresponding CTA. Both readers were blinded to all clinical information and the other scans at the time of the ratings. Discrepancies about the occurrence of BS and SS were settled by joint discussion of the 2 readers. The hematoma BS was defined as recently published.6 In brief, it represents a hematoma with a hyperdense and a hypodense area, which show a well-defined margin that is easily recognized by the naked eye. There should be a difference of at least 18 HU between the 2 regions, and the hypodense area should not be encapsulated by the hyperdense part of the hematoma (Figure 1).
The ICH volumes of the baseline CT were segmented using Analyze (Analyze 10.0; AnalyzeDirect Inc, Overland Park, KS). We, therefore, extracted the DICOM data of CT scans and implemented them into Analyze. Here, the hematoma volume was segmented slice by slice.
Univariable distribution of metric variables is described by median and interquartile range. For categorical data, absolute and relative frequencies are given. Mann–Whitney U test or χ2 test was used to compare 2 independent samples on a metric or categorical outcome, respectively. McNemar test was used to assess differences between paired portions.
Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of BS and SS are given with exact 95% confidence interval. The underlying goldstandard is neurological deterioration (yes or no) as defined above in the Patients section. Discrepancies about the occurrence of BS and SS were settled by joint discussion of the 2 readers. McNemar test was used to compare sensitivity and specificity of BS and SS. To compare PPV and NPV of BS and SS, the test of Leisenring et al9 was used. Cohen κ was used to measure inter-rater agreement about the occurrence of BS and SS.
Logistic regression analysis was performed to assess the association between the clinical and radiological parameters and neurological deterioration. Multivariable model building was performed using a stepwise variable selection procedure: in a first step, all factors were fitted together by a stepwise forward selection (inclusion: P value of the score test ≤0.05 and exclusion: P value of the likelihood ratio test >0.1). Then, the factors of the model from step 1 were fitted together with all pairwise interactions in a second block using stepwise forward selection (inclusion: P value of the score test ≤0.05 and exclusion: P value of the likelihood ratio test >0.1). Given for selected variables are odds ratios with 95% confidence interval and P value of likelihood ratio test. For nonselected variables, P value of score test is displayed. Odds were calculated as ratio of the probability for secondary deterioration to the probability for no deterioration.
No adjustment for multiple testing was performed, and analyses are regarded as explorative. Local, unadjusted P values <0.05 were considered as statistically noticeable.
Statistical analyses were performed in SPSS version 23 (IBM Corporation, Armonk, NY) and in SAS 9.4 (SAS Institute, Cary, NC).
A total of 182 patients fulfilled the inclusion criteria; no patients had to be excluded from the analysis. The median age of the patients was 68 years (interquartile range, 54–79). A total of 83 (45.6%) were female, and 99 (54.4%) were male. Secondary neurological deterioration was observed in 81 patients (44.5%) with ICH. The median hematoma volume was 22.4 mL and differed noticeably between patients with secondary deterioration (median 38.85 mL) and no deterioration (median 11.25 mL; P≤0.001). The hematoma was mostly located in the basal ganglia (47.8%), followed by cerebral lobes (44.5%), brain stem (3.3%), and cerebellum (4.4%). Moreover, we obtained risk factors such as hypertension and diabetes mellitus. Analyses revealed statistically noticeable impact of intraventricular hemorrhage (P≤0.001) and hematoma volume (P≤0.001) on distribution of secondary neurological deterioration (Table 1). Additional analyses showed that in the current patient collective 151 of 182 patients had received primary imaging at our center, and 31 patients were transferred to our tertiary stroke center secondarily.
Secondary Neurological Deterioration of Patients With BS and SS and Interobserver Agreement
Of the 182 patients, 81 (44.5%) showed a secondary neurological deterioration within 48 hours. In 31 (38.3%) out of 81 patients with secondary deterioration, BS could be detected on NCCT, and in 31 (38.3%) patients, SS could be detected in CTA.
Of 182 patients with spontaneous ICH, 37 (20.3%) presented with BS and 39 (21.4%) with SS on initial imaging. Twenty-nine patients showed both BS and SS. Of these 29 patients, 25 (86.2%) had a secondary deterioration. In contrast, only 44 of 135 patients (32.6%) without initial SS or BS showed a secondary deterioration within 48 hours (Figure 2).
Inter-rater agreement for identifying BS and SS was very high between the 2 readers (BS: κ=0.984; SS: κ=0.965). Discrepancies between the 2 readers on SS (BS) were present in 1(2) patient(s).10
The sensitivity, specificity, PPV, and NPV of BS for predicting secondary deterioration were 38.3%, 94.1%, 83.3%, and 65.5% and for SS 38.3%, 92.1%, 79.5%, and 65.0% (Table 2). BS and SS both appeared in 29.7% of the ICH that later on had a secondary deterioration. BS showed slightly higher specificity, PPV, and NPV in the basal ganglia (96.0%, 84.6%, and 64.9%) compared with SS (92.0%, 73.3%, and 63.9%). However, differences between BS and SS on sensitivity, specificity, PPV, and NPV were not statistically noticeable (Table 2).
Logistic regression analysis was performed to assess the association between various clinical and radiological parameters and secondary neurological deterioration. In univariable logistic regression, higher baseline hematoma volume (P≤0.001), intraventricular hemorrhage (P=0.002), and the presence of BS and SS (both P≤0.001) on admission CT scan were associated with secondary deterioration (Table 3). The multivariable logistic regression analysis confirmed higher baseline hematoma volume (odds ratio, 1.07 per mL; P≤0.001), intraventricular hemorrhage (odds ratio, 3.08; P=0.008), and the presence of BS on baseline CT (odds ratio, 11.47; P≤0.001) scan as independent predictors of secondary deterioration (Table 4). SS on baseline CT was not selected as independent predictor for secondary deterioration in multivariable analysis (P=0.346) in view of high correlation between the deterioration predictions based on BS and SS. Prediction was discrepant between BS and SS for 18 out of 182 patients (P=0.815). This supports good performance of both BS and SS in prediction of secondary neurological deterioration (Table 4).
Our results show that the novel CT BS is a promising new imaging parameter for prediction of a secondary neurological deterioration in patients with ICH. Prevalence of BS in our study was 20.3% and comparable to other studies6 and the prevalence of SS was 21.4%.7 Best independent predictors of secondary neurological deterioration detection rates were baseline hematoma volume, intraventricular hemorrhage, and the presence of BS on baseline CT.
Especially, in a setting where CTA is not readily available or with strong contraindications for contrast application (distinct allergy and far progressed renal dysfunction), sole acquisition of NCCT and evaluation of BS are reliable options for the detection of hematoma growth associated with secondary neurological deterioration. The high inter-rater reliability suggests that BS is an easy-to-use new imaging parameter.
Limitations of our study are because of its retrospective nature and single-center design. Moreover, in studies investigating on emergencies such as hemorrhagic stroke, standardized diagnostic and therapeutic procedures are difficult to establish. Because of that neurological deterioration measurements may have been more or less objective in some cases. Long-term follow-up, including more standard outcome measures such as modified Rankin scale, might offer additional information but was not available for this study.
However, the large patient population and the similar results compared with previous studies investigating on the predictive values of BS and SS suggest a high reliability and importance of these imaging parameters for prediction of secondary neurological deterioration in patients with ICH.
The CT BS, which is obtainable in NCCT shows a very high association with the CTA SS and is a reliable predictor of secondary neurological deterioration after spontaneous ICH. In a setting, where CTA is not readily available, it offers a reliable alternative to the well-established SS.
The final decision for this article was made by Ralph L. Sacco, MD.
- Received May 20, 2016.
- Revision received October 4, 2016.
- Accepted October 19, 2016.
- © 2016 American Heart Association, Inc.
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