Edema Extension Distance

Perihematomal edema (PHE) complicates acute spontaneous intracerebral hemorrhage (ICH) and can increase mass effect, contributing to early neurological deterioration and poor outcome.1,2 The innate immune response within the brain is a key driver of PHE and is characterized by the activation of resident microglia by damage-associated molecular patterns, infiltration of peripheral immune cells, and the production of inflammatory mediators, all of which increase tissue damage and promote blood–brain barrier breakdown.3 Following the well-documented failure to translate treatments for ischemic stroke from experimental studies to clinical use, early-phase clinical trials to demonstrate proof-of-concept in clinical stroke have been recommended before definitive phase III trials.4 Edema has been widely used as the main outcome to test interventions in preclinical ICH,5 so has considerable appeal as an outcome measure for such early-phase clinical trials. PHE can be reliably and objectively measured using noncontrast computed tomography,6,7 so can be collected easily and cheaply from almost all patients with ICH. However, ICH and PHE volumes are closely correlated,2,6,8 so variation in hematoma volume introduces variation in PHE volume. Unlike experimental ICH (where hematoma volume is tightly controlled by the investigator), hematoma volumes in clinical ICH are highly variable, introducing variability in PHE volumes and increasing the sample size required to demonstrate a given treatment effect. The use of relative PHE volume (PHE volume÷ICH volume) has been suggested as a solution to this, but tends to be disproportionately high for smaller hematomas and has thus been advised against.6 Here, we present a solution to this problem that will allow researchers to demonstrate a reduction in PHE with a much smaller sample size, thus potentially accelerating translational ICH research with reduced costs.As the factors driving edema (eg, damage-associated molecular patterns) are …