Abstract
Background and ObjectivesSmall 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.MethodsIn 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 z score-derived composite outcome score using quantile regression.ResultsAmong 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, p = 0.005). Higher lesion counts were associated with worse day 1 NIHSS (adjusted odds ratio for NIHSS ≥1: 1.07, 1.02-1.12, p = 0.009), day 2-4 mRS (adjusted common odds ratio [acOR] 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 (acOR 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-day 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, whereas day 2-4 MMSE correlated with 30-day NIHSS and DSST scores (Spearman ρ 0.47, p = 0.001).DiscussionIatrogenic 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 InformationClinical trials registration NCT00728182.
| Original language | English |
|---|---|
| Pages (from-to) | E1446-E1458 |
| Journal | Neurology |
| Volume | 98 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - Apr 5 2022 |
Bibliographical note
Funding Information:A. Ganesh reports funding from the Wellcome Trust, Canadian Institutes of Health Research, Canadian Cardiovascular Society, Campus Alberta Neuroscience, and Alberta Innovates; consultation fees from Atheneum, MD Analytics, MyMedicalPanel, Creative Research Designs, and DeepBench; and stock options from SnapDx, TheRounds.com , and Advanced Health Analytics (AHA Health Ltd). M. Goyal reports personal fees from Medtronic, Stryker, Microvention, and Mentice during the conduct of the study; unrestricted research grants to University of Calgary from NoNO, Stryker, and Medtronic; patents for a system of acute stroke diagnosis, with royalties paid to GE Healthcare, and a system of simulation for acute neurointervention, with royalties paid to Mentice; and ownership interest in Circle Neurovascular. A.T. Wilson and J.M. Ospel report no disclosures. A.M. Demchuk reports grants from NoNO Inc., a patent to Circle NVI, issued; and honoraria for CME events from Medtronic. D. Mikulis reports shares in NoNO Inc., and, outside this work, multiple imaging patents and grant support from The Centre for Aging and Brain Health Innovation, GE Healthcare, The American Society of Neuroradiology, and the Holt-Hornsby and Andreae Vascular Dementia Research Unit at the University Health Network. J. Poublanc and T. Krings report no disclosures. R. Anderson was the VP of Clinical Development at NoNO during the time this study was conducted and is now a salaried employee of Syneos Health. M. Tymianski is the CEO of NoNO and is the inventor of patents owned by NoNO. M.D. Hill reports grants from Canadian Institutes for Health Research, Alberta Innovates, and NoNO, for the conduct of the study; personal fees from Merck; nonfinancial support from Hoffmann-La Roche Canada; grants from Covidien (Medtronic), Boehringer-Ingelheim, Stryker, and Medtronic, outside the submitted work; a patent for systems and methods for assisting in decision-making and triaging for patients with acute stroke, issued to US patent office number 62/086,077; owns stock in Calgary Scientific; is a director of the Canadian Federation of Neurological Sciences and Circle NeuroVascular; and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart & Stroke Foundation of Canada, and the National Institutes of Neurological Disorders and Stroke. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© American Academy of Neurology.
ASJC Scopus Subject Areas
- Clinical Neurology
PubMed: MeSH publication types
- Journal Article
- Randomized Controlled Trial