Andrea Morotti, MD
Intracerebral Hemorrhage (ICH) is a dynamic disease, with up to half of the patients experiencing active bleeding in the acute phase. Hematoma growth represents a potential therapeutic target to improve patients’ outcome. Rapid identification of subjects at high risk of hematoma growth is, therefore, crucial in clinical practice and in the setting of clinical trials testing anti-expansion treatments. The CT angiography (CTA) spot sign is a robust marker of ICH expansion. However, CTA is not available in many institutions, and a large proportion of ICH patients do not receive a CTA as part of their diagnostic workup 1. This highlights the need for novel markers of hematoma growth that do not require a CTA.
Using a well-characterized cohort including 252 ICH patients, Qi Li and colleagues described the island sign, a novel marker of hematoma growth that can be evaluated on baseline non-contrast CT (NCCT). The island sign was defined as presence of at least 3 scattered small hematomas all separate from the main hemorrhage or at least 4 small hematomas, some or all of which may be connected with the main hemorrhage. An illustrative example of the island sign is provided in Figure 1. ICH expansion was defined as hematoma growth > 6mL or > 33% from baseline hematoma volume.
The prevalence of this marker was 16.3% in the entire study population, and its frequency was significantly higher in patients experiencing ICH expansion (44.7% vs 1.8%, p<0.001). After adjustment for known predictors of hematoma growth, the presence of NCCT island sign remained independently associated with a high risk of hematoma expansion (odds ratio 31.98, p<0.001). The island sign showed excellent specificity for ICH growth (98.2%) but suboptimal sensitivity (44.7%), meaning that more than half of the patients experiencing hemorrhage growth do not have any evidence of this marker. This imaging marker was also independently associated with greater odds of poor functional outcome (odds ratio 3.51, p<0.001).
The results of this study may have relevant implications for future studies on ICH expansion because it seems possible to predict ICH expansion without a CTA. This may expand the pool of patients eligible for clinical trials aiming at reducing hematoma growth. The island sign correlated with poor prognosis as well. Accurate estimation of ICH prognosis remains a daily challenge for stroke physicians and an easy-to-use and widely available NCCT marker may improve the ability to predict unfavorable prognosis.
Some limitations should be considered. First, the island sign was described in a single-center cohort with a relatively small sample size, without a validation population. Second, anticoagulant-associated hemorrhages were excluded. This may have influenced the results because warfarin-associated coagulopathy is a well-known predictor of hemorrhage growth. Third, there is significant overlap between different NCCT markers that have been recently described, suggesting the need for a consensus on the diagnostic criteria for the identification of these signs.2,3
In conclusion, this study described a novel imaging marker of hemorrhage growth that can be evaluated on NCCT. Prospective validation is required, along with integration and comparison with other NCCT and CTA-based markers of hemorrhage growth.
- Morotti A, Brouwers HB, Romero JM, et al. Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage. JAMA Neurol. 2017; 74:950-960.
- Boulouis G, Morotti A, Charidimou A, Dowlatshahi D, Goldstein JN. Noncontrast Computed Tomography Markers of Intracerebral Hemorrhage Expansion. Stroke. 2017;48:1120-1125.
- Barras CD, Tress BM, Christensen S, et al. Density and shape as CT predictors of intracerebral hemorrhage growth. Stroke. 2009;40:1325-1331.