Abstract Body: BACKGROUND: Acute ischemic stroke is a leading cause of death and disability in the U.S. Mechanical thrombectomy (MT) has transformed care for patients with small or moderate core infarcts and recently expanded to include those with large infarcts, demonstrating both functional and survival benefits. Despite this, many patients undergoing MT still experience significant disability or death. The discovery of novel adjuvant pharmacotherapies is increasingly critical as MT indications broaden. This study aimed to identify proteomic expression patterns in large core infarct patients undergoing MT to inform potential pharmacological intervention targets.

METHODS: The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) tissue registry was reviewed for anterior circulation MT patients treated between June 2017-December 2023. Patients with an initial Alberta Stroke Program Early CT Score (ASPECTS) > 6 were compared to those with ASPECTS < 6. The primary outcome was the development of malignant cerebral edema (MCE), defined as edema with any degree of midline shift secondary to a completed infarct in the intracranial internal carotid or middle cerebral artery territories.

RESULTS: One hundred and thirty patients were eligible for out study of which 15 (11.5%) had ASPECTS <6. Patients with ASPECTS <6 were younger (60.5 vs 67.5 years, p=0.04) and more likely to have history of myocardial infarction (27% vs 4%, p=0.01), higher NIHSS on admission (26 vs 17, p<0.0001) and discharge (25 vs 7, p<0.0001) when compared to patients with ASPECTS>6. Other baseline demographics were comparable. Ten patients (66.6%) with ASPECTS<6 developed MCE versus 11 patients (9.5%) with ASPECTS>6 (p<0.0001). In MCE patients those with ASPECTS<6 had significantly higher expression of FGF 21, DPP4 and NT-3 (p=0.02, 0.04 and 0.04, respectively) and lower expression of IGFBP6 and TWEAK (P=0.006 and 0.03, respectively).

CONCLUSION: Patients with large core infarcts (ASPECTS <6) undergoing MT are at a significantly higher risk of developing malignant cerebral edema. The differential expression of proteomic markers such as FGF 21, DPP4, NT-3, IGFBP6, and TWEAK in these patients suggests potential targets for pharmacological intervention. These findings highlight the need for further research into neuroprotective strategies to improve outcomes in this high-risk population.