OBJECTIVE: To investigatethe prevalence, predictors and prognostic impact of hematoma expansion (HE) inintracerebral hemorrhage (ICH) patients with unclear symptom onset (USO).
METHODS: Retrospective analysis of patients with primary spontaneous ICH admitted at 5 academic medical centers in USA and Italy.HE (volume increase >6 mL and/or >33% from baseline to follow-up non-contrast CT [NCCT]) and mortality at 30 days were the outcomes of interest. Baseline NCCT was also analyzed for presence of hypodensities (any hypodense region within the hematoma margins). Predictors of HE and mortality were explored with multivariable logistic regression.
RESULTS: We enrolled 2,165 subjects, 1,022 in the development cohort and 1,143 in the replication cohort, of whom 352 (34.4%) and 407 (35.6%) had ICH with USO respectively. When compared with subjects having a clear symptom onset, USO patients had a similar frequency of HE (25.0% vs 21.9%, p = 0.269 and 29.9% vs 31.5%, p = 0.423). Among USO patients, HE was independently associated with mortality after adjustment for confounders (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.43-4.89, p = 0.002). This finding wassimilar in the replication cohort (OR 3.46, 95% CI 1.86-6.44, p < 0.001). The presence of NCCT hypodensities in USO subjects was an independent predictor of HE in the development (OR 2.59, 95% CI 1.27-5.28, p = 0.009) and replication (OR 2.43, 95% CI 1.42-4.17, p = 0.001) population.
CONCLUSION: HE is common in USO patients and independently associated with worse outcome. These findings suggest that USO patients may be enrolled in clinical trials on medical treatments targeting HE.