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Introduction: Oedema extension distance is a derived parameter that may reduce sample size requirements to demonstrate reduction in perihaematomal oedema in early phase acute intracerebral haemorrhage trials. We aimed to identify baseline predictors of oedema extension distance and its association with clinical outcomes. Patients and methods: Using Virtual International Stroke Trials Archive-Intracerebral Haemorrhage, first Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial, and Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation II datasets, we calculated oedema extension distance at baseline and at 72 h measured using computed tomography. Using linear regression, we tested for associations between baseline characteristics and oedema extension distance at 72 h. Ordinal regression (underlying assumptions validated) was used to test for associations between oedema extension distance at baseline and 72 h and oedema extension distance change between baseline and 72 h, and modified Rankin scale scores at 90 days, adjusted for baseline and 72 h prognostic factors. Results: There were 1028 intracerebral haemorrhage cases with outcome data for analyses. Mean (standard deviation, SD) oedema extension distance at 72 h was 0.54 (0.26) cm, and mean oedema extension distance difference from baseline (EED72-0) was 0.24 (0.18) cm. Oedema extension distance at 72 h was greater with increasing baseline haematoma volume and baseline oedema extension distance. Increasing age, lobar haemorrhage, and intraventricular haemorrhage were independently associated with EED72-0. In multifactorial ordinal regression analysis, EED72-0 was associated with worse modified Rankin scale scores at 90 days (odds ratio 1.96, 95% confidence interval 1.00-3.82). Discussion: Increase in oedema extension distance over 72 h is independently associated with decreasing functional outcome at 90 days. Oedema extension distance may be a useful surrogate outcome measure in early phase trials of anti-oedema or anti-inflammatory treatments in intracerebral haemorrhage.

Original publication




Journal article


Eur Stroke J

Publication Date





263 - 270


Intracerebral haemorrhage, inflammation, oedema, surrogate markers