Severity of leukoaraiosis determines clinical phenotype after brain infarction

Abstract

Objective: To determine whether the extent of leukoaraiosis, a composite marker of baseline brain integrity, differed between patients with TIA with diffusion-weighted imaging (DWI) evidence of infarction (transient symptoms with infarction [TSI]) and patients with ischemic stroke.Methods: Leukoaraiosis volume on MRI was quantified in a consecutive series of 153 TSI and 354 ischemic stroke patients with comparable infarct volumes on DWI. We explored the relationship between leukoaraiosis volume and clinical phenotype (TIA or ischemic stroke) using a logistic regression model. Results:Patients with TSI tended to be younger (median age 66 vs 69 years, p ϭ 0.062) and had smaller median normalized leukoaraiosis volume (1.2 mL, interquartile range [IQR] 0.2-4.7 mL vs 3.5 mL, IQR 1.2-8.6 mL, p Ͻ 0.001). In multivariable analysis controlling for age, stroke risk factors, etiologic stroke mechanism, infarct volume, and infarct location, increasing leukoaraiosis volume remained associated with ischemic stroke (odds ratio 1.05 per mL, 95% confidence interval 1.02-1.09, p ϭ 0.004), along with infarct volume and infarct location. Conclusion:The probability of ischemic stroke rather than TSI increases with increasing leukoaraiosis volume, independent of infarct size and location. Our findings support the concept that the integrity of white matter tracts connecting different parts of the brain could contribute to whether or not patients develop TSI or ischemic stroke in an event of brain infarction. Neurology Approximately one-third of traditionally defined TIAs present with imaging evidence consistent with acute infarction (now termed transient symptoms with infarction [TSI]).1 Rapid and complete clinical recovery in TSI suggests that the brain has the ability to quickly compensate for the neurologic dysfunction caused by underlying infarcts. One of the most characteristic features of TSI-related infarcts is that they are invariably very small 2 ; 96% of all infarcts in TSI are smaller than 1 mL. While small infarcts are frequent in TSI, they are not specific; such small infarcts also occur in patients with clinical deficits lasting for more than 24 hours (traditionally defined ischemic stroke).2 Furthermore, small infarcts in TSI do not occur solely in so-called silent brain regions but can also involve the same brain structures that are often infarcted in ischemic stroke.2 Hence, it is not known how neurologic symptoms rapidly recover in some patients, but do not in others, despite the evidence of cerebral infarction of similar size and in similar location.Functional recovery after brain injury is a complex process which involves recruitment and reorganization of structures that are functionally similar but anatomically distinct from those that are infarcted. [3][4][5] Prior observations suggest that the integrity of the white matter as quanti-*These authors contributed equally to this work.From the A.A.

Extensive Leukoaraiosis Is Associated With High Early Risk of Recurrence After Ischemic Stroke

“…However, the association between leukoaraiosis and recurrent stroke risk cannot be explained solely on the basis of shared risk factors because the present study and previously published studies clearly indicate that leukoaraiosis is a predictor of stroke risk even after controlling for by guest on May 9, 2018 http://stroke.ahajournals.org/ Downloaded from vascular risk factors. 2,13,15,23 Of note, none of the conventional factors except for hypertension that confer an increased risk in the long-term predicted stroke recurrence in the short-term in the present study, consistent with the notion that leukoaraiosis influences short-term risk of recurrent stroke through other mechanisms. Prior studies have suggested that the extent of leukoaraiosis can negatively affect the brain's capacity to tolerate an ischemic insult; among patients with cerebral ischemia, those with extensive leukoaraiosis are more likely to develop completed cerebral infarction, 6 and among patients with acute infarction, those with extensive leukoaraiosis are more likely to develop severe and persistent clinical deficits.…”

“…Prior studies have suggested that the extent of leukoaraiosis can negatively affect the brain's capacity to tolerate an ischemic insult; among patients with cerebral ischemia, those with extensive leukoaraiosis are more likely to develop completed cerebral infarction, 6 and among patients with acute infarction, those with extensive leukoaraiosis are more likely to develop severe and persistent clinical deficits. 1,2 Given that asymptomatic new infarcts are substantially more common, as much as 17× more common-than symptomatic infarcts during the first few days after an ischemic stroke, 24 impaired ability of the brain to tolerate ischemia and its reduced capacity to compensate for the lost function in the presence of extensive leukoaraiosis could potentially facilitate conversion of asymptomatic infarcts into symptomatic infarcts. In support of this view, procedures that are associated with high risk of embolism to the brain, such as carotid artery stenting, 25,26 carotid endarterectomy, 26,27 and total aortic arch replacement, 28 confer a higher perioperative risk of symptomatic stroke in patients with extensive leukoaraiosis when compared with those with less severe leukoaraiosis.…”

“…1,2 An earlier study has shown that, in an event of acute brain infarction, the odds of developing severe and persistent symptoms when compared with mild and transient symptoms increases with increasing volume of leukoaraiosis. 2 A shift toward more severe strokes by increasing leukoaraiosis severity suggests that acute infarcts otherwise destined to remain inconspicuous would be more clinically apparent in the presence of leukoaraiosis. In other words, the presence of leukoaraiosis may facilitate detection of new ischemic events occurring after an initial ischemic stroke by making them more clinically noticeable.…”

Severity of leukoaraiosis, leptomeningeal collaterals, and clinical outcomes after intra-arterial therapy in patients with acute ischemic stroke

“…Severity of LA was assessed using a previously published semi-automated volumetric analysis method with high inter-rater reliability 13. MRI were acquired on 1.5 T Signa scanners (GE Medical Systems, Milwaukee, Wisconsin, USA), and all scans were converted to analyze format using MRIcro software (University of Nottingham School of Psychology, Nottingham, UK, http://www.mricro.com).…”

“…MRI were acquired on 1.5 T Signa scanners (GE Medical Systems, Milwaukee, Wisconsin, USA), and all scans were converted to analyze format using MRIcro software (University of Nottingham School of Psychology, Nottingham, UK, http://www.mricro.com). Computer assisted determination of LA volume (LAv) included: (a) creating LA maps using axial T2 fluid attenuated inversion recovery sequences, (b) aligning these maps with the corresponding diffusion weighted imaging (DWI) sequences for exclusion of acute ischemia, edema, and chronic territorial infarcts, and (c) calculating the total LAv by doubling the LAv in the hemisphere unaffected by the stroke and adjusted for head size, as previously described 13. All images in this study were assessed by two investigators (NSR and KF) prospectively, with the sample intraclass correlation coefficient for LAv of 0.97, and blinded to patient CTA characteristics, recanalization status, and clinical outcomes.…”