BACKGROUND 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 multi-variable models to evaluate the association of the presence and number of iatrogenic infarcts on DWI with neurological impairment (National Institutes of Health Stroke Scale[NIHSS]), functional status (modified Rankin Scale[mRS]), cognitive and neuropsychiatric outcomes (30-minute test battery) at 1-4 days and 30-days post-procedure. We also related infarct number to a Z-score-derived composite outcome score using quantile regression. RESULTS Among 184 patients (median age 56,IQR 50-64), 124 (67.4%) had post-procedural 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 Exam(MMSE) scores at 2-4 days (median 28 vs 29, adjusted-coefficient[acoef]: -1.11, 95%CI -1.88 to -0.34,p=0.005). Higher lesion counts were associated with worse day-1 NIHSS (aOR for NIHSS≥1:1.07, 1.02-1.12,p=0.009), day 2-4 mRS (adjusted common odds-ratio[aOR]: 1.05,1.01-1.09,p=0.005), and day 2-4 MMSE (acoef:-0.07,-0.13 to -0.003,p=0.040) scores. At 30-days, infarct number remained associated with worse mRS (aOR:1.04,1.01-1.07,p=0.016) and Hopkins Verbal Learning Test(HVLT) delayed-recall scores (acoef:-0.21,-0.39 to -0.03,p=0.020). Patients with infarcts trended towards lower 30-day Digit Symbol Substitution Test(DSST) scores (acoef:-3.73,-7.36 to -0.10,p=0.044). Higher lesion count was associated with worse composite outcome scores at both 1-4 days and 30-days (30-days acoef:-0.12,95%CI -0.21 to -0.03,p=0.008). Among those with infarcts, day-1 NIHSS and day 2-4 mRS correlated with 30-day NIHSS, DSST, HVLT, and mRS scores, whilst day 2-4 MMSE correlated with 30-day NIHSS and DSST scores (Spearman-Rho:0.47,p=0.001). CONCLUSIONS Iatrogenic brain infarcts were associated with subtle differences in post-procedural (1-4 days) and 30-day outcomes on different measures in this middle-aged cohort, with earlier dysfunction correlating with later differences. CLINICAL TRIALS REGISTRATION ClinicalTrials.gov, number NCT00728182.
Association of Iatrogenic Infarcts With Clinical and Cognitive Outcomes in the Evaluating Neuroprotection in Aneurysm Coiling Therapy Trial.