Department of Neurology, University of Texas Health Science Center at Houston (A.S., D.P.).
Departments of Neurology and Neurological Sciences (M. Mlynash, J.H., M.L., G.W.A.).
Stroke. 2021 Mar;52(3):838-849. doi: 10.1161/STROKEAHA.120.031147. Epub 2021 Feb 10.
DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) infarct volumes at 24 hours did not significantly differ in the endovascular thrombectomy (EVT) versus medical management (MM) only groups. We hypothesized that this was due to underestimation of the final infarct volume among patients with persistent penumbral tissue 24 hours after randomization that subsequently progressed to infarction. We sought to assess the clinical outcomes in patients with persistent penumbral profile >24 hours from last known well and identify them based on the Persistent Penumbra Index (PPI, time-to-maximum of the residue function >6 s perfusion lesion divided by diffusion-weighted magnetic resonance imaging lesion volume on 24-hour postrandomization imaging).
Patients were stratified into those with a 24-hour postrandomization penumbral (PPI>1) versus a nonpenumbral (PPI≤1) profile. The primary outcome was 90-day-modified Rankin Scale.
One hundred eighty-two patients were randomized (EVT: 92, MM: 90). Twenty-four-hour postrandomization time-to-maximum of the residue function and infarct volumes were assessable for 144 (EVT: 75, MM: 69). Infarct volumes did not differ between EVT and MM (median [interquartile range] mL: 35.0 [17.6-81.6] versus 41.0 [25.4-106.2], =0.185). Thirty-two patients had persistent penumbral profile (PPI>1), of these 29 (91%) received MM. PPI was 0 (0-0.07) for EVT, and 0.77 (0.23-1.79) for MM, <0.001. Patients with clinical-imaging mismatch (more severe strokes and smaller infarct volumes) were more likely to have persistent penumbral profile (PPI>1; adjusted odds ratio, 1.20 [1.11-1.30] for every 1-point National Institutes of Health Stroke Scale-increment and adjusted odds ratio, 0.977 [0.964-0.990] for every 10 cc smaller infarct volume, <0.001). Patients with nonpenumbral profile (PPI≤1) had higher odds of achieving functional independence (39% versus 9%; adjusted odds ratio, 9.9[95% CI, 2.3-42.8], =0.002), a trend towards lower mortality (12% versus 34%, =0.002; adjusted odds ratio, 0.34 [95% CI, 0.11-1.03], =0.057) and early clinical improvement (24-hour National Institutes of Health Stroke Scale-decrease ≥8 points or 0-1): 29% vs 9%, =0.034) which persisted at discharge and 90-day follow-up. For a given volume, patients with PPI≤1 had significantly higher likelihood of functional independence as compared to those with PPI>1.
Patients with persistent penumbral profile who have salvageable tissue beyond 24 hours from last known well can be identified by PPI and clinical-imaging mismatch. They have a poor prognosis and may benefit from very late window reperfusion therapies. Clinical trials in these patients are warranted. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.
DEFUSE 3 试验（缺血性脑卒中血管内治疗后影像学评估 3）结果显示，血管内治疗组（EVT）与单纯药物治疗组（MM）在 24 小时时的梗死体积没有显著差异。我们推测，这是由于随机分组后 24 小时仍存在持续性半暗带组织的患者的最终梗死体积被低估，随后进展为梗死。我们旨在评估在最后一次已知状态后 24 小时仍存在持续性半暗带影像的患者的临床结局，并根据持续半暗带指数（PPI，最大残差功能时间至 6 s 灌注损伤除以 24 小时后随机化的弥散加权磁共振成像损伤体积）来识别这些患者。
患者被分为 24 小时后存在半暗带（PPI＞1）和非半暗带（PPI≤1）的患者。主要结局是 90 天改良 Rankin 量表评分。
182 名患者被随机分配（EVT：92 例，MM：90 例）。144 例患者（EVT：75 例，MM：69 例）可评估 24 小时后最大残差功能时间和梗死体积。EVT 和 MM 之间的梗死体积没有差异（中位数[四分位数范围]，mL：35.0[17.6-81.6]与 41.0[25.4-106.2]，=0.185）。32 例患者存在持续性半暗带影像（PPI＞1），其中 29 例（91%）接受了 MM 治疗。EVT 的 PPI 为 0（0-0.07），MM 的 PPI 为 0.77（0.23-1.79），<0.001。具有临床-影像不匹配（更严重的脑卒中且梗死体积更小）的患者更可能存在持续性半暗带影像（PPI＞1；每增加 1 分 NIHSS 评分，调整后的优势比为 1.20[1.11-1.30]；每减少 10cc 梗死体积，调整后的优势比为 0.977[0.964-0.990]，均<0.001）。具有非半暗带影像（PPI≤1）的患者更有可能实现功能独立（39%比 9%；调整后的优势比为 9.9[95%CI，2.3-42.8]，=0.002），死亡率较低的趋势（12%比 34%，=0.002；调整后的优势比为 0.34[95%CI，0.11-1.03]，=0.057），以及早期临床改善（24 小时 NIHSS 评分降低≥8 分或 0-1：29%比 9%，=0.034），这些结果在出院和 90 天随访时仍然存在。对于给定的体积，PPI≤1 的患者比 PPI＞1 的患者更有可能实现功能独立。
在最后一次已知状态后 24 小时仍存在可挽救组织的持续性半暗带影像患者，可以通过 PPI 和临床-影像不匹配来识别。他们的预后较差，可能受益于非常晚期的再灌注治疗。这些患者的临床试验是必要的。注册：网址：https://www.clinicaltrials.gov。唯一标识符：NCT02586415。
