Piyush Ojha, MBBS, MD, DM

Law ZK, Ali A, Krishnan K, Bischoff A, Appleton JP, Scutt P, et al. Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome, and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage. Stroke. 2020;51:121–128.

Spontaneous intracerebral hemorrhage (ICH) remains a major cause of morbidity and mortality worldwide. Hematoma expansion affects 30-40% of patients with acute ICH within the first few hours of onset; hence, its prevention is an important treatment target in acute ICH care to prevent neurological worsening and poor long-term outcome, thus necessitating more close neurological monitoring. Although the presence of spot sign in Computed Tomography (CT) angiography predicts hematoma expansion, only a minority of ICH patients receives contrast injection during the initial imaging. Since non-contrast CT (NCCT) is widely available and used, NCCT markers represent an important alternative for prediction of hematoma expansion. 

NCCT signs can be divided into density markers (swirl sign, blend sign, black hole sign, hypodensity and fluid level) and shape markers (irregular shape, island sign and satellite sign).

Various observational studies, RCT populations and meta-analyses have suggested that NCCT signs markers might be reliable predictors of hematoma expansion and poor outcome in ICH, but with different effect size and strength of association.

The Tranexamic acid for IntraCerebral Hemorrhage-2 (TICH-2) trial was a prospective randomized placebo-controlled trial testing the efficacy and safety of intravenous tranexamic acid in patients with acute spontaneous ICH presenting within 8 hours of symptom onset.

Zhe Kang Law et al. analyzed various NCCT signs in predicting hematoma expansion and functional outcome in acute ICH patients. They evaluated the baseline and 24-hour computed tomography scans of the enrolled patients. Hematoma expansion was defined as an increase in hematoma volume of >33% or >6 mL on 24-hour CT. Poor functional outcome was defined as modified Rankin Scale(mRS) of 4 to 6 at 3 months.

Out of all the 2077 patients with a valid baseline and 24-hour scans, 570 patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. NCCT signs were more common in patients with hematoma expansion compared to those without it. Among the various NCCT signs studied, hypodensities were present in approximately 30% of patients while black hole sign, blend sign and island sign were present in 18.2%, 16.1% and 8.8% of patients, respectively. All the NCCT signs had low sensitivity but high specificity for both hematoma expansion and poor functional outcome, with island sign being most specific for the hematoma expansion.

Participants with hematoma expansion had higher baseline NIHSS, lower GCS, larger baseline hematoma volumes, more lobar location, prior antiplatelet therapy, a shorter onset-to-CT time and less intraventricular component.

Blend sign, black hole sign and presence of hypodensities were independent predictors of hematoma expansion whereas black hole sign, hypodensities and island sign were significant predictors of poor functional outcome. A combination of 1 or more NCCT signs did not improve the predictive probability of either hematoma expansion or poor functional outcome. Although tranexamic acid reduced the risk of hematoma expansion (p=0.010), there was no significant interaction between the presence of these NCCT signs and benefit of tranexamic acid on hematoma expansion and functional outcomes.

The authors, hence, concluded that blend sign, black hole sign and hypodensities were independent predictors of hematoma expansion. Nevertheless, addition of these signs to more established predictors of onset-to-CT time, baseline hematoma volume, and prior antiplatelet therapy only marginally improved the area under the curve. NCCT signs did not predict a better response to tranexamic acid.

Since the NCCT signs which predicted hematoma expansion and poor functional outcome were not exactly alike, it was suggested that there are additional factors which contribute to poor functional outcome in addition to hematoma expansion. This observation is also reflected in the finding that, although tranexamic acid significantly reduced hematoma expansion, early death and serious adverse events, it did not improve long-term functional outcome. The observation that none of the NCCT signs reliably predicted clinical benefit of tranexamic acid again supports an additional pathological process contributing to poor outcome.

The strength of the study was the large sample size and varied baseline hematoma values in the patients enrolled similar to a real-life scenario.

The limitations of the study were moderate inter-rater agreement, probably due to different background of the raters and more than two raters, which is unlike many other studies. Another limitation could be a lack of standard definition for the standard signs.

Future studies prospectively evaluating the inter- and intra-rater reliability of NCCT markers would be useful. Also, studies using these NCCT signs to select patients more likely to benefit from hemostatic treatment or intensive blood pressure lowering measures would be interesting as a large number of patents can be enrolled compared to the studies using spot sign.