Impact of Brain Frailty on Clinical Presentation and Neurologic Recovery in Acute Ischemic Stroke Patients Undergoing Thrombectomy

Brain frailty impairs the ability to compensate for brain dysfunction and is linked to worse outcomes after stroke. Stroke severity at presentation is a key determinant of outcomes in acute ischemic stroke. This study aimed to examine the impact of brain frailty on initial stroke severity and recovery in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT). We conducted a post hoc analysis of the ESCAPE-NA1 randomized-controlled trial that investigated the efficacy and safety of the neuroprotectant nerinetide in patients with AIS who received EVT. Brain frailty markers (cortical atrophy, subcortical atrophy, white matter hyperintensities, chronic infarcts) were visually assessed from baseline noncontrast CT scans. We explored the association between these markers and admission stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) using multivariable quantile regression. We also assessed the NIHSS trajectory over 90 days using repeated-measures analysis. Models were adjusted for relevant covariates. Among 1,102 participants (mean age 69.5 years; 49.7% female), NIHSS scores at baseline were higher in patients with cortical atrophy and those with chronic infarcts compared with patients having no cortical atrophy or chronic infarcts after adjusting for confounders (adjusted difference for GCA1 vs GCA0 = 1.25 points [95% CI 0.18-2.31], p = 0.021; adjusted difference for presence of chronic infarcts = 1.27 points [95% CI 0.007-2.53, p = 0.049]). Subcortical atrophy, white matter hyperintensity burden, lacunes, and overall brain frailty were not associated with NIHSS scores at presentation. A repeated-measures analysis showed consistent higher NIHSS scores in individuals with brain frailty compared with those without, after the acute phase throughout the 90-day follow-up period (NIHSS score at 30 days, adjusted difference for total brain frailty score 1 vs 0 = 1.16 points [95% CI 0.35-1.96], p = 0.01; brain frailty score 2/3 vs 0 = 0.98 [95% CI 0.08-1.88], p = 0.03; NIHSS score at 90 days (adjusted difference for brain frailty score 1 vs 0 = 0.97 [95% CI 0.19-1.75], p = 0.01; brain frailty score 2/3 vs 0 = 0.85 [95% CI -0.01 to -1.71], p = 0.05). This study highlights the association of brain frailty with the clinical presentation and recovery trajectory of patients with AIS undergoing EVT. Specifically, cortical atrophy was independently associated with baseline stroke severity, and the total burden of brain frailty was independently associated with NIHSS recovery trajectories. The results emphasize the importance of considering brain frailty in acute stroke management and prognostication.