Association of Brain Atrophy With Functional Outcome and Recovery Trajectories After Thrombectomy: Post-Hoc Analysis of the ESCAPE-NA1 Trial

BACKGROUND AND OBJECTIVES: Brain frailty may impair the ability of acute stroke patients to cope with the injury, irrespective of their chronological age, resulting in impaired recovery. We aim to investigate the impact of brain atrophy on functional outcome assessed at different time points after EVT. METHODS: In this retrospective post-hoc analysis of the ESCAPE-NA1-trial, we analyzed CT-imaging data for cortical atrophy by using the GCA-scale, including region-specific scales, and subcortical atrophy by using the intercaudate-distance-to-inner-table-width (CC/IT)- ratio. The primary outcome was 90-day-mRS (ordinal-shift-analysis) and the secondary outcome was the mRS-score over time. Adjustments were made for age, sex, baseline-NIHSS, final infarct volume, stroke laterality, total Fazekas score and nerinetide-alteplase interaction. Sensitivity analyses were additionally performed in only those patients for whom MRI-data were available. RESULTS: Out of 1,102 participants (mean age of 69.5±13.7 years;554 men), 818 (74%) had GCA=0, 220 (20%) had GCA=1 and 64 (6%) GCA=2/3. The median CC/IT-ratio was 0.12(IQR0.10-0.15). Cortical atrophy(GCA=1 vs GCA-0) was associated with worse 90-day-mRS (acOR=1.62[95%CI:1.22-2.16]; p=001), lower rates of 90-day-mRS0-2 (aOR=0.65[95%CI:0.45-0.94]; p=0.022) and higher mortality (aOR=2.12[95%CI:1.28-3.5]; p=0.003), regardless of the region assessed. Subcortical atrophy was associated with worse 90-day-mRS(acOR[per 0.01 increase in CC/IT-ratio]=1.07[95%CI:1.04-1.11]; p<0.001) and lower rates of 90-day mRS0-2(aOR=0.92[95%CI:0.88-0.97]; p=0.001). Furthermore, with various degrees of atrophy, we observed heterogeneity in mRS-measurements during follow-up: worse mRS scores for higher atrophy grades(p<0.001). Compared to participants with GCA=0, the mRS for participants with GCA=1 was higher at 30-days (adjusted-difference=0.41[95%CI:0.18-0.65]) and remained worse at 90-days (adjusted-difference=0.72[95%CI:0.49-0.95]). Similar effects were seen for participants with worse cortical atrophy, regardless of the region assessed, and worse subcortical atrophy. Furthermore, 26/63(41%) and 124/274(45%) of patients with severe cortical/subcortical atrophy (GCA-2/-3 and highest CC/IT-ratio quartile, respectively) achieved good functional outcome(mRS0-2), compared to 539/812(66.4%) with no cortical atrophy and 209/274(76%) in the lowest CC/IT-ratio quartile. DISCUSSION: In this large RCT-derived population, participants with brain atrophy, as visually assessed on acute NCCT-imaging, showed less favorable stroke recovery after EVT and worse 90-day functional outcomes compared to participants without brain atrophy. This may support physicians with recovery expectations when planning post-EVT care with patients and their families.