Supplementary Material for: Accuracy of the Spot Sign on Computed Tomography Angiography as a Predictor of Haematoma Enlargement after Acute Spontaneous Intracerebral Haemorrhage: A Systematic Review

<b><i>Background:</i></b> A common early complication of intracerebral haemorrhage (ICH) is haematoma enlargement (HE), a strong independent predictor of a poor outcome. Therapeutic options to limit haematoma progression are currently scarce. Haemostatic therapy may be effective in patients with ICH, but it carries the risk of thromboembolic events in unselected patients. Accurate patient selection would, therefore, be of key importance for delivering potentially successful therapeutic strategies. Currently, there is no gold standard to accurately predict HE. The presence of contrast extravasation within the haematoma on computed tomography angiography (CTA), the ‘spot sign', has been reported in several studies and seems a particularly promising marker but lacks a standardised evaluation so far. <b><i>Summary:</i></b> We conducted a systematic review of published data to address the research question: In adults with acute spontaneous ICH, how accurately does the spot sign predict HE on follow-up imaging and thus poor functional outcome or mortality? We searched PubMed and Embase databases (from 1980 to May 2012), using a highly sensitive search strategy and including all studies involving adult patients with spontaneous ICH evaluated with CTA and follow-up CT scans, reporting any measure of clinical outcome, and reporting or allowing calculation of accuracy measures of the spot sign in predicting HE and clinical outcome. Baseline characteristics, accuracy measures and effect measures, as well as bias assessment, were reported according to PRISMA recommendations. The quality of the studies was appraised using an adapted version of the REMARK reporting recommendations. From 259 potentially relevant studies, we finally selected 6 studies (1 of them was a multicentre cohort study) covering a total of 709 patients. Studies varied substantially in terms of size, methodological quality, definitions of terms, outcomes selected and results. In particular, definition of the spot sign was not consistent in all studies. Furthermore, the only outcome measure consistently available was HE, while definitions and analyses of clinical outcomes seemed not adequate. Lastly, the choice of candidate variables for univariate and multivariate analyses did not include all determinants of HE and poor functional outcome. High heterogeneity was demonstrated (I<sup>2</sup>: 94% for HE) with substantial potential of bias. <b><i>Key Messages:</i></b> Studies of the spot sign are diverse and therefore complex to interpret. Our research question could not be answered due to heterogeneity and potential of bias in the selected studies. Further appropriately powered studies using standardised definitions and taking all predictors of HE and poor clinical outcome into account are required for a proper clinical implementation.