Perihaematomal oedema (PHO) is an important pathophysiological marker of secondary injury in intracerebral haemorrhage (ICH). In this Review, we describe a novel method to conceptualize PHO formation within the framework of Starling's principle of movement of fluid across a capillary wall. We consider progression of PHO through three stages, characterized by ionic oedema (stage 1) and progressive vasogenic oedema (stages 2 and 3). In this context, possible modifiers of PHO volume and their value in identifying patients who would benefit from therapies that target secondary injury are discussed; the practicalities of using neuroimaging to measure PHO volume are also considered. We examine whether PHO can be used as a predictor of neurological outcome following ICH, and we provide an overview of emerging therapies. Our discussion emphasizes that PHO has clinical relevance both as a therapeutic target, owing to its augmentation of the mass effect of a haemorrhage, and as a surrogate marker for novel interventions that target secondary injury.

Objective Intracerebral hemorrhage (ICH) is a devastating disorder with no current treatment. Whether peri-hematomal edema (PHE) is an independent predictor of neurologic outcome is controversial. We sought to determine whether PHE expansion rate predicts outcome after ICH. Design Retrospective cohort study Setting Tertiary medical center Patients 139 consecutive supratentorial spontaneous ICH patients >18 years admitted between 2000–2013. Interventions None Measurements and Main Results ICH, intraventricular hemorrhage (IVH), and PHE volumes were measured from computed tomography (CT) scans obtained at presentation, 24 hours, and 72 hours post-ICH. PHE expansion rate was the difference between initial and follow-up PHE volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) PHE expansion rate at 24 hours and 90-day mortality and 2) PHE expansion rate at 24 hours and 90-day modified Rankin Scale score (mRS). PHE expansion rate between admission and 24-hours post-ICH was a significant predictor of 90-day mortality (OR 2.97, 95%CI 1.48–5.99, p=0.002). This association persisted after adjusting for all components of the ICH score (OR 2.21, 95% CI 1.05–4.64, p=0.04). Similarly, higher 24-hour PHE expansion rate was associated with poorer mRS in an ordinal shift analysis (OR 2.40, 95% CI 1.37–4.21, p=.002), even after adjustment for all ICH score components (OR 2.07, 95% CI 1.12–3.83, p=0.02). Conclusions Faster PHE expansion rate 24 hours post-ICH is associated with worse outcome. PHE may represent an attractive translational target for secondary injury after ICH.

Background Perihaematomal oedema (PHE) expansion rate may be a predictor of outcome after intracerebral haemorrhage (ICH). We determined whether PHE expansion rate in the first 72 hours after ICH predicts outcome, and how it compares against other PHE measures. Methods We included patients from the Virtual International Stroke Trials Archive. We calculated PHE expansion rate using the equation: (PHE at 72 hours- PHE at baseline)/(Time to 72 hour computerized tomography scan – Time to baseline computerized tomography scan). Outcomes of interest were mortality and poor 90-day outcome (modified Rankin Scale score of ≥ 3). Logistic regression was used to assess relationships with outcome. Results A total of 596 patients with ICH were included. At baseline, median haematoma volume was 15.0 mL (IQR: 7.9–29.2) with median PHE volume of 8.7 mL (IQR: 4.5–15.5). Median PHE expansion rate was 0.31 mL/hr (IQR: 0.12–0.55). The odds of mortality were greater with increasing PHE expansion rate (OR: 2.63, CI: 1.10–6.25), while the odds of poor outcome also increased with greater PHE growth (OR: 1.67, CI: 1.28–2.39). Female sex had an inverse relationship with PHE growth, but baseline hematoma volume had a direct correlation. Among other PHE measures, only interval increase in PHE correlated with poor outcome. There was no significant difference between the two measures of PHE volume expansion. Conclusions Rate of PHE growth over 72 hours was an independent predictor of mortality and poor functional outcomes following intracerebral haemorrhage. Baseline haematoma volume and gender appear to influence PHE growth.

Background and Purpose Peri-hematomal edema (PHE) is a marker of secondary injury in intracerebral hemorrhage (ICH). PHE measurement on computed tomography (CT) is challenging and the principles used to detect PHE have not been described fully. We developed a systematic approach for CT-based measurement of PHE. Methods Two independent raters measured PHE volumes on baseline and 24-hour post-ICH CT scans of twenty primary supratentorial ICH subjects. Boundaries were outlined with an edge-detection tool and adjusted after inspection of the three orthogonal planes. PHE was delineated with the additional principle that it should be (a) more hypodense than the corresponding area in the contralateral hemisphere and (b) most hypodense immediately surrounding the hemorrhage. We examined intra- and interrater reliability using intraclass correlation coefficients (ICCs) and Bland-Altman plots for interrater consistency. CT-based PHE was also compared using MRI-based PHE detection for eighteen subjects. Results Median PHE volumes were 22.7 cc at baseline and 20.4 cc at 24-hours post-ICH. There were no statistically significant differences in PHE measurements between raters. Interrater and intrarater reliability for PHE were excellent. At baseline and 24-hours, interrater ICCs were 0.98 (0.96–1.00) and 0.98 (0.97–1.00); intrarater ICCs were 0.99 (0.99–1.00) and 0.99 (0.98–1.00). Bland-Altman analysis showed the bias for PHE measurements at baseline and 24 hours, −0.5 cc (SD, 5.4) and −3.2 cc (SD, 5.0), was acceptably small. PHE volumes determined by CT and MRI were similar (23.9 ± 16.9 cc vs. 23.9 ± 16.0 cc, R2 = 0.98, p < 0.0001). Conclusions Our method measures PHE with excellent reliability at baseline and 24-hours post-ICH.