Danny R. Rose, Jr., MD

Dowlatshahi D, Brouwers HB, Demchuk AM, Hill MD, Aviv RI, Ufholz L-A, et al. Predicting Intracerebral Hemorrhage Growth With the Spot Sign: The Effect of Onset-to-Scan Time. Stroke. 2016

Intracerebral hemorrhage (ICH) causes a significant amount of stroke-related morbidity and mortality. Of the various prognostic factors in ICH, hematoma expansion 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. One of the more promising diagnostic features in identifying such patients is the “spot sign” of contrast extravasation in the hematoma bed of ICH patients undergoing CT angiography (CTA). However, the predictive value of the spot sign has differed widely across studies, which may reflect variability in delay between ictus and CTA acquisition. Dowlatshahi et al. sought to examine the predictive value of the spot sign in relationship to onset-to-CTA times in patients with acute ICH by conducting a systematic review and patient-level meta-analysis.

The authors found eight studies in which patient-level data was able to be obtained regarding spot sign status, baseline and follow-up hematoma volumes and time from onset to presentation and CTA. Onset-to-CTA time was categorized a priori into five strata: <120 minutes, 120-239 minutes, 240-359 minutes, 360-479 minutes, and >480 minutes.  Hematoma size was measured by computer-assisted planimetry in three studies and the ABC/2 in five studies. A total of 1343 patients were evaluated across the eight studies, with 1176 having baseline hematoma volumes, spot sign status and time-to-CTA, 1039 of whom had follow-up hematoma volume measurements. 
There was significant heterogeneity of spot sign frequency among the studies (I2 = 20.67, p=0.004), due to heterogeneity in the 0-2h (I2 = 15.5, p=0.016) and the 2-4h stratas (I2 = 16.5, p=0.011). There was no heterogeneity for the later time strata. The frequency of the spot sign was 26% for the group as a whole with a significant relationship with onset-to-CTA time strata (p<0.001), decreasing from 39% within two hours of onset to 13% after eight hours. There was no heterogeneity in hematoma expansion between studies (F=0.45, p=0.87) or time strata (F=0.75, p=0.56). Across all time intervals, the median volume of hematoma expansion was greater for spot positive as compared to spot negative patients, and there was no change in median hematoma expansion by time-strata in spot positive patients (F=1.28, p=0.14). Spot positivity and significant hematoma expansion (defined as 6mL or ≥33%) as onset-to-CTA time strata increased. Sensitivity and PPV of the spot sign for hematoma expansion was greatest in the earlier time strata, whereas the specificity and negative predictive value (NPV) of spot sign increased with time. 

This study suggests that the utility of spot sign assessment may be dichotomized depending on onset-to-CTA time. The earlier time strata had the highest sensitivity and PPV which both decreased with time, and the later time strata suggested a high specificity and NPV. Identifying patients at risk for hematoma expansion as well as patients who likely have stable hematomas are both of value to clinicians, and understanding this information in the context of CTA timing suggests clinically relevant information can be gleaned regardless of the time of onset-to-CTA. Even in the acute setting, however, the best sensitivity to detect hematoma expansion was only 60%. This suggests that the spot sign alone is insufficient to identify at-risk patients and should be incorporated into future studies designed to identify other potential predictive factors. As the authors were unable to include any studies published after 2013 due to the time needed to acquire regulatory approvals for patient-level data, analysis of more recent studies would be helpful to validate these results.