Andrea Morotti, MD

Al-Shahi SR, Frantzias J, Lee RJ, Lyden PD, Battey TWK, Ayres AM, et al. Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data. Lancet Neurol. 2018;17:885–894.

Intracerebral Hemorrhage (ICH) expansion is common, independently associated with poor outcome and potentially preventable, representing, therefore, an appealing target for acute ICH treatment.

In this large (n = 5435) meta-analysis of individual patient data,1 the authors identified the following four independent predictors of ICH expansion: time from symptom onset to baseline non-contrast CT (NCCT) (odds ratio 0.50, p<0∙0001), baseline hematoma volume (odds ratio 7.18, p<0∙0001), antiplatelet treatment (odds ratio 1.68, p=0∙026), and anticoagulant use (3.48, p<0∙0001). These predictors had a good discrimination for hematoma expansion (c statistic 0.78). A small proportion (around 16%) of the included patients had CT angiography (CTA) images available for spot sign detection. In this subgroup, the presence of spot sign provided a small but significant additional diagnostic value compared to a model based only on the four predictors described above (c statistic 0.83).

Another very interesting result is the non linear association of ICH volume and NCCT timing with the odds of hematoma expansion. In particular, the risk of hemorrhage growth peaked at baseline hematoma volume around 75 mL, and the predicted probability of hemorrhage growth declined steeply in the first 3 hours after symptom onset.

The results of this paper may have important implications for future clinical trials testing therapeutic strategies to limit hematoma expansion. Less than one in five ICH patients usually receives a CTA,2,3 and a prediction model based on four easily available variables showed a good diagnostic performance in the stratification of hematoma expansion risk.

Hematoma expansion is a very early event in the natural history of acute ICH, leaving a narrow window for the administration of treatments directed at limiting active bleeding. Several ICH trials (ATACH-2, INTERACT-2, TICH) delivered anti-expansion treatments with an average time beyond 3 hours from onset,3–5 highlighting the need to reduce the time from symptom onset to ICH diagnosis and management.

Some limitations should be considered. First, different definitions of CTA spot sign have been described, with different prevalence and test characteristics. Second, the CTA acquisition protocol for spot sign detection may influence the diagnostic performance of this imaging marker.6 Third, more than half of the eligible cohorts declined to provide individual patient data for this study, raising the possibility of selection bias. Finally, several NCCT markers of ICH expansion have been described and may represent a reliable alternative to the CTA spot sign for detection of subjects at high risk of hemorrhage growth.7

In conclusion, four easily available variables allow an accurate stratification of ICH expansion risk. If CTA is available, spot sign detection provides a small but relevant additional diagnostic value. More research is needed to test whether NCCT markers of ICH expansion can improve the currently available models.


  1. Al-Shahi Salman R, Frantzias J, Lee RJ, et al. Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data. Lancet Neurol. 2018;17(10):885–894.
  2. Morotti A, Brouwers HB, Romero JM, et al. Intensive blood pressure reduction and spot sign in intracerebral hemorrhage: A secondary analysis of a randomized clinical trial. JAMA Neurol. 2017;74(8):950-960.
  3. Sprigg N, Flaherty K, Appleton JP, et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet. 2018;391(10135):2107-2115.
  4. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016;375(11):1033-43.
  5. Anderson C, Heeley E, Huang Y, et al. Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage. N Engl J Med. 2013;368(25):2355–2365.
  6. Morotti A, Romero JM, Jessel MJ, et al. Effect of CTA Tube Current on Spot Sign Detection and Accuracy for Prediction of Intracerebral Hemorrhage Expansion. AJNR Am J Neuroradiol. 2016;37(10):1781-1786.
  7. Boulouis G, Morotti A, Charidimou A, et al. Noncontrast Computed Tomography Markers of Intracerebral Hemorrhage Expansion. Stroke 2017;48(4):1120–1125.