Abstract Background and aims Perihematomal hypoperfusion has been considered a benign oligoemic state; however, emerging evidence suggests that it may represent an ischemic penumbra with potential progression to irreversible injury. This evolution may result from the combined effects of perfusion abnormalities and neuroinflammatory mediators of secondary brain injury. This study aims to characterize the pathophysiology of perihematomal hypoperfusion. The primary objective is to assess the association between acute-phase perfusion parameters and the development of ischemic lesions in the subacute phase. Secondary objectives are to evaluate the role of plasmatic mediators—including NADPH oxidase, an oxidative stress –related enzyme, and vasoactive molecules (endothelin-1 and nitric oxide)—in the development of perihematomal hypoperfusion and ischemic damage, and to assess their associations with hematoma and edema evolution and clinical outcomes. Imaging and plasmatic biomarkers may identify patients at increased risk of secondary injury. Methods We will enroll 124 patients with spontaneous ICH presenting to the Emergency Department of Umberto I Hospital, Rome, within 12 hours of symptom onset. CT perfusion/angiography will be performed, together with blood sampling for biomarkers analysis. Conventional (Tmax, rCBF/rCBV), microvascular and metabolic (OEF, CMRO2) perfusion parameters will be quantified in the perihematomal hypoperfusion area using Cercare Medical Neurosuite® software. A non-contrast CT at 24 hours will assess hematoma and edema volume evolution. MRI at 7 days will be performed to detect secondary ischemic lesions. Clinical outcome will be assessed by mRS at 3 months. Results The project is under review by the local ethics committee and will be initiated upon approval. Conflict of interest Paolo Amisano: recipient of the HippOnion–ISA AII 2025 Grant. Svetlana Lorenzano: nothing to disclose. Ettore Nicolini: advisory board member for CERCARE Medical and speaker honoraria from Boehringer Ingelheim. Antonio Ciacciarelli: speaker honoraria from the Angels Initiative. Marta Iacobucci: nothing to disclose. Danilo Toni: advisory board participation and speaker’s honoraria from Alexion, AstraZeneca, Boehringer Ingelheim, Medtronic, and Pfizer. Manuela De Michele: nothing to disclose.
Amisano et al. (Fri,) studied this question.
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