Supplementary Material for: Pre-Stroke Frailty Negatively Affects Leptomeningeal Collateral Flow in Proximal Middle Cerebral Artery Occlusion

Introduction: The adequacy of blood flow from the leptomeningeal collaterals is considered one of the most important factors determining the rate of infarct progression and response to acute stroke treatments in the setting of large vessel occlusions. Several patient-related variables, including age, vascular risk factors, and laboratory parameters, have been proposed to explain the interindividual variability of collateral flow among stroke patients. This study aimed to assess how pre-stroke frailty, an aging-related syndrome characterized by a loss in the physiologic reserve of numerous body functions, affected the degree of leptomeningeal collateral flow in the setting of acute ischemic stroke. Methods: A consecutive series of patients presenting with proximal middle cerebral artery occlusion were enrolled in this prospective, multi-center observational study. Collateral flow was determined by the Regional Leptomeningeal Collateral (rLMC) Score on admission computed tomography angiography images. Pre-stroke frailty was assessed by the Edmonton Frailty Scale (EFS), based on the information obtained from patients or their next of kin. The relationship between collateral flow and frailty was evaluated by bivariate and multivariate analyses taking into consideration the demographic, clinical and imaging characteristics of the patients. Results: The study population was comprised of 116 patients (median (IQR) age 78 (71-84) years; 60% female). The EFS scores were negatively correlated with the rLMC score (r=-0.264; p=0.004). A vulnerable or frail (EFS≥6) status before stroke, higher blood pressure levels at admission, having imaging studies performed at an earlier phase after contrast injection, and presenting with thrombi extending to the proximal half of the M1 portion of the middle cerebral artery were significantly related to poor collateral circulation (rLMC score ≤10). After adjustment for potential confounders in multivariable analyses, a vulnerable/frail status was independently associated with poor leptomeningeal collateral flow [OR 2.97 (95%CI 1.15-7.69); p=0.025]. Conclusion: Our findings highlight that the leptomeningeal collateral flow is also compromised as part of the diminished physiologic reserve characterizing the frailty status in patients with acute ischemic stroke. Future studies are needed to understand how this interplay contributes to the unfavorable clinical outcomes observed in frail patients after stroke.