Intracerebral hemorrhage (ICH) causes a significant amount of stroke-related morbidity and mortality. Of the various prognostic factors in ICH, hematoma expansion (HE) is one of the few potentially modifiable ones and as such has been a topic of increasing research. Unfortunately, large-scale randomized controlled trials aimed at preventing hematoma expansion have not shown robust results, possibly owing to the limited ability of clinicians to predict which patients are at greatest risk. The “spot sign,” a radiographic sign representing the leakage of contrast with a hematoma on CT scan has recently become a topic of extensive study with respect to its ability to predict hematoma expansion. As described previously, a recently published meta-analysis suggested that the sensitivity and positive predictive value of the spot sign was related to the time from ictus to scan acquisition and may not adequately predict HE when it is detected. Additionally, other studies have shown that using CT perfusion (CTP) improves the detection rate of the spot sign. Wang et al. sought to explore the relationship between spot sign characteristics on CTP (including number, timing, and maximum density) to evaluate the relationship between these characteristics and the risk of HE as well as clinical outcome.
The authors’ retrospectively reviewed a total of 83 patients from a prospectively collected database of consecutive patients with supratentorial SICH. Patients receiving surgical evacuation of their hematoma were excluded from the outcome analysis, and additionally were excluded from HE analysis if the intervention took place prior to the 24 h follow-up CT scan. Patients who died prior to the 24 h follow-up CT scan were excluded from the HE analysis.  Patients with secondary causes of ICH were also excluded. A total of eleven patients (6 with positive spot sign) were excluded from the HE analysis, and twelve patients (7 with positive spot sign) were excluded from outcome analysis due to receiving surgical evaluation. Excluded patients had higher SBP and DBP, over a three-fold greater median hematoma volume (52.30 mL vs 15.80 mL, P=0.029) and a nearly two-fold higher median NIHSS (21 vs 11, P=0.004). 

Baseline clinical variables included patient demographics, medical history, medications, onset to imaging time (OIT), baseline National Institute of Health Stroke Scale (NIHSS), and laboratory results. The clinical outcomes assessed were NIHSS at 24 h, in-hospital mortality, and modified Rankin Scale (mRS) including death at 3 months follow-up. Spot sign was assessed with CTP and the timing of occurrence (time from the start of scan to first detection of spot sign), total number of spots, maximum spot attenuation, and axial dimensions were recorded. The median time of onset to CP was 180 (120 to 240) minutes. Hematoma expansion was defined as an absolute ICH growth ≥ 6 mL or relative growth ≥ 33% as recorded on 24 h follow-up CT scan. 

The rate of spot sign was higher in patients with HE than those without (62.5% vs 12.5%, P<0.001). The presence of spot sign was independently associated with HE after correcting for APTT, glucose, NIHSS, baseline hematoma volume, and antiplatelet use. There was a trend for an association between the presence of spot sign and 3-month mortality (32% vs 8%, OR=5.649; 95% CI 0.913-34.954; P=0.063) after multivariate analysis. Spot sign was detected much earlier in patients with HE than those without (18.75 s vs 26.87 s, P=0.007). The timing of spot sign was significantly correlated with both absolute and relative ICH volume growth, and there was no association between the other spot sign characteristics and HE. The authors defined a subset of spot sign patients as having an “early occurring spot sign (EOSS),” defined as detection of the spot sign before 23.13 seconds. EOSS was found to have 0.67 sensitivity and 0.90 specificity for HE. On multivariate analysis, EOSS was an independent predictor of HE (OR=28.835; 95% CI, 6.960-119.458; P<0.001) and 3-month mortality (OR=22.377, 95% CI, 1.773-282.334; P=0.016). EOSS maintained a higher specificity for HE compared to spot sign (91% vs 74%).

In this single-center cohort of SICH patients, spot sign as assessed by CTP was associated with HE. The authors also found that early detection of the spot sign was the most important characteristic with respect to predicting HE and significantly correlated with ICH growth. The primary limitations of the study were related to the retrospective nature of the study, the relatively small sample size, and the use of a single center for recruitment and determining imaging parameters. External validation with a larger sample size and standardized imaging parameters will be necessary. In addition, the high rate of excluded surgical evacuation patients with positive spot sign may have led to an underestimation of the spot sign’s PPV with respect to mortality. It is also important to note that the predictive value and associations with spot sign on CTP in this study should not be applied patients evaluated with single-phase CT angiography. However, replicating this study with multi-phase CTA could be feasible and represents a potential future avenue of research.