Background and Purpose: The spot sign score (SSS) stratifies hematoma expansion risk in patients with acute intracerebral hemorrhage (ICH) but is not externally validated. We sought to validate the SSS and assess prognostic spot characteristics associated with hematoma expansion in a prospective multicenter study. Methods: We studied 228 ICH patients presenting < 6 hours post-onset enrolled in the PREDICT (PREdicting hematoma growth anD outcome in ICH using contrast bolus CT) study, a multicentre prospective observational cohort study of ICH patients evaluated with baseline non-contrast CT, CT angiography (CTA), and 24-hour follow-up CT. Primary outcome was significant hematoma expansion (>6ml or >33%). Secondary outcomes were absolute and relative expansion. Blinded CTA spot sign characterization (spot number, maximum axial size and attenuation, and relative attenuation compared to the ipsilateral internal carotid artery and superior sagittal sinus) and SSS calculation was performed independently by two neuroradiologists and a radiology resident. Multivariable regression for prediction of hematoma expansion was performed and diagnostic performance of the SSS and spot characteristics was examined with ROC analysis and tests for trend. Results: SSS independently predicted significant, absolute, and relative hematoma expansion (p-values of 0.001, <0.001, and 0.009, respectively), adjusting for initial hematoma volume, INR, mean arterial pressure, and time from onset-to-baseline CT, and demonstrated near perfect interobserver agreement (κ = 0.82). Spot number and SSS demonstrated similar area under the curve (AUC 0.69 vs. 0.68, p=0.149) for hematoma expansion. Incremental risk of hematoma expansion was demonstrated with increasing SSS however a significant trend was not identified (p trend=0.720). Of all spot characteristics, only spot number was independently associated with expansion (p<0.001) providing incremental risk stratification (p trend=0.050) and near perfect agreement (κ=0.85). Median absolute hematoma growth for 0, 1, 2 to 3, ≥4 spots was 0.4, 4, 12, 82 ml respectively. Conclusion: Spot number is the single best predictor of significant ICH expansion and appears to be as good as the total SSS in predicting expansion.
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