在动脉瘤栓塞治疗试验中评估神经保护作用时医源性梗死与临床及认知结局的关联
Association of Iatrogenic Infarcts With Clinical and Cognitive Outcomes in the Evaluating Neuroprotection in Aneurysm Coiling Therapy Trial.
作者信息
Ganesh Aravind, Goyal Mayank, Wilson Alexis T, Ospel Johanna Maria, Demchuk Andrew M, Mikulis David, Poublanc Julien, Krings Timo, Anderson Roberta, Tymianski Michael, Hill Michael D
机构信息
From the Calgary Stroke Program, Department of Clinical Neurosciences (A.G., M.G., A.T.W., J.M.O., A.M.D., M.D.H.), Department of Community Health Sciences (A.G., M.D.H.), Hotchkiss Brain Institute (A.G., M.G., A.M.D., M.D.H.), and Department of Radiology (M.G., A.M.D., M.D.H.), University of Calgary, Canada; Department of Radiology (J.M.O.), University Hospital Basel, University of Basel, Switzerland; Department of Medical Imaging (D.M., J.P.) and Division of Neuroradiology (T.K.), Toronto Western Hospital, University Health Network and University of Toronto; NoNO Inc. (R.A., M.T.), Toronto; Division of Neurosurgery and Neurovascular Therapeutics Program (M.T.), University Health Network, Toronto; Departments of Surgery and Physiology (M.T.), University of Toronto; Toronto Western Hospital Research Institute (M.T.); and Department of Medicine (M.D.H.), University of Calgary Cumming School of Medicine, Canada.
出版信息
Neurology. 2022 Apr 5;98(14):e1446-e1458. doi: 10.1212/WNL.0000000000200111. Epub 2022 Feb 15.
BACKGROUND AND OBJECTIVES
Small iatrogenic brain infarcts are often seen on diffusion-weighted MRI (DWI) following surgical or endovascular procedures, but there are few data on their clinical effects. We examined the association of iatrogenic infarcts with outcomes in the ENACT (Evaluating Neuroprotection in Aneurysm Coiling Therapy) randomized controlled trial of nerinetide in patients undergoing endovascular repair of intracranial aneurysms.
METHODS
In this post hoc analysis, we used multivariable models to evaluate the association of the presence and number of iatrogenic infarcts on DWI with neurologic impairment (NIH Stroke Scale [NIHSS]), functional status (modified Rankin Scale [mRS]), and cognitive and neuropsychiatric outcomes (30-minute test battery) at 1-4 days and 30 days postprocedure. We also related infarct number to a score-derived composite outcome score using quantile regression.
RESULTS
Among 184 patients (median age 56 years [interquartile range (IQR) 50-64]), 124 (67.4%) had postprocedural DWI lesions (median 4, IQR 2-10.5). Nerinetide treatment was associated with fewer iatrogenic infarcts but no overall significant clinical treatment effects. Patients with infarcts had lower Mini-Mental State Examination (MMSE) scores at 2-4 days (median 28 vs 29, adjusted coefficient [acoef] -1.11, 95% CI -1.88 to -0.34, = 0.005). Higher lesion counts were associated with worse day 1 NIHSS (adjusted odds ratio for NIHSS ≥1: 1.07, 1.02-1.12, = 0.009), day 2-4 mRS (adjusted common odds ratio [acOR] 1.05, 1.01-1.09, = 0.005), and day 2-4 MMSE (acoef -0.07, -0.13 to -0.003, = 0.040) scores. At 30 days, infarct number remained associated with worse mRS (acOR 1.04, 1.01-1.07, = 0.016) and Hopkins Verbal Learning Test (HVLT) delayed recall scores (acoef -0.21, -0.39 to -0.03, = 0.020). Patients with infarcts trended towards lower 30-day Digit Symbol Substitution Test (DSST) scores (acoef -3.73, -7.36 to -0.10, = 0.044). Higher lesion count was associated with worse composite outcome scores at both 1-4 days and 30 days (30-day acoef -0.12, 95% CI -0.21 to -0.03, = 0.008). Among those with infarcts, day 1 NIHSS and day 2-4 mRS correlated with 30-day NIHSS, DSST, HVLT, and mRS scores, whereas day 2-4 MMSE correlated with 30-day NIHSS and DSST scores (Spearman ρ 0.47, = 0.001).
DISCUSSION
Iatrogenic brain infarcts were associated with subtle differences in postprocedural (1-4 days) and 30-day outcomes on different measures in this middle-aged cohort, with earlier dysfunction correlating with later differences.
TRIAL REGISTRATION INFORMATION
Clinical trials registration NCT00728182.
背景与目的
在外科手术或血管内介入治疗后，扩散加权磁共振成像（DWI）上常可见到小的医源性脑梗死，但关于其临床影响的数据较少。我们在ENACT（颅内动脉瘤血管内修复术中神经保护评估）随机对照试验中，研究了医源性梗死与接受颅内动脉瘤血管内修复术患者结局之间的关联，该试验使用了神经肽。
方法
在这项事后分析中，我们使用多变量模型来评估DWI上医源性梗死的存在和数量与术后1 - 4天及30天时的神经功能缺损（美国国立卫生研究院卒中量表[NIHSS]）、功能状态（改良Rankin量表[mRS]）以及认知和神经精神结局（30分钟测试组）之间的关联。我们还使用分位数回归将梗死数量与一个得分衍生的综合结局评分相关联。
结果
在184例患者（中位年龄56岁[四分位间距（IQR）50 - 64]）中，124例（67.4%）术后DWI出现病变（中位4个，IQR 2 - 10.5）。神经肽治疗与医源性梗死较少相关，但总体上无显著的临床治疗效果。有梗死的患者在术后2 - 4天的简易精神状态检查表（MMSE）评分较低（中位28分对29分，调整系数[acoef] -1.11，95%置信区间 -1.88至 -0.34，P = 0.005）。更高的病变数量与术后第1天更差的NIHSS（NIHSS≥1的调整优势比：1.07，1.02 - 1.12，P = 0.009）、术后第2 - 4天更差的mRS（调整共同优势比[acOR] 1.05，1.01 - 1.09，P = 0.005）以及术后第2 - 4天更差的MMSE（acoef -0.07， -0.13至 -0.003，P = 0.040）评分相关。在30天时，梗死数量仍与更差的mRS（acOR 1.04，1.01 - 1.07，P = 0.016）和霍普金斯言语学习测验（HVLT）延迟回忆评分（acoef -0.
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