Leukoaraiosis Predicts Poor 90-Day Outcome after Acute Large Cerebral Artery Occlusion

Abstract

Background: To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. Methods: We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007–2010) at a single academic institution. The final study cohort included 87 patients with acute ILAO subjected to multimodal CT imaging within 24 h of symptom onset. LA severity was assessed using the van Swieten scale on non-contrast CT. Leptomeningeal collaterals were graded using CT angiogram source images. Hemorrhagic transformation (HT) was determined on follow-up CT. Multivariate logistic regression controlling for HT, treatment modality, demographic, as well as baseline clinical and imaging characteristics was used to identify independent predictors of a poor outcome (90-day mRS >2). Results: The median National Institutes of Health Stroke Scale (NIHSS) at baseline was 15 (interquartile range 9–21). Twenty-four percent of the studied patients had severe LA. They were more likely to have hypertension (p = 0.028), coronary artery disease (p = 0.015), poor collaterals (p < 0.001), higher baseline NIHSS (p = 0.003), higher mRS at 90 days (p < 0.001), and were older (p = 0.002). Patients with severe LA had a uniformly poor outcome (p < 0.001) irrespective of treatment modality. Poor outcome was independently associated with higher baseline NIHSS (p < 0.001), worse LA (graded and dichotomized, p < 0.001), reduced leptomeningeal collaterals (graded and dichotomized, p < 0.001), presence of HT (p < 0.001), presence of parenchymal hemorrhages (p = 0.01), baseline mRS (p = 0.002), and older age (p = 0.043). The association between severe LA (p = 0.0056; OR 13.86; 95% CI 1.94–∞) and baseline NIHSS (p = 0.0001; OR 5.11; 95% CI 2.07–14.49 for each 10-point increase) with poor outcome maintained after adjustment for confounders in the final regression model. In this model, there was no significant association between presence of HT and poor outcome (p = 0.0572). Conclusion: Coexisting LA may predict poor functional outcome in patients with acute anterior circulation ILAO independent of other known important outcome predictors such as comorbid state, admission functional deficit, collateral status, hemorrhagic conversion, and treatment modality.

Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke

“…36 Global WM integrity may also play a role in compensatory mechanisms of early and long-term poststroke recovery, as has been suggested by studies on overt WMH burden. 4,23,37 In line with this hypothesis, our findings of reduced FA in the contralateral NAWM being associated with functional recovery implicate a contribution from WM integrity to poststroke recovery. Supporting our findings, in patients in the chronic state of recovery from left hemisphere ischemic stroke, FA values in specific regions of interest in the contralateral hemisphere (middle temporal gyrus, precentral gyrus, and pars opercularis) were predictive of speech fluency.…”

“…22 In addition, WMH burden deleteriously affects functional outcomes at 1 to 12 months after ischemic stroke and is associated with greater likelihood of long-term disability. [3][4][5][23][24][25] There is a growing body of evidence, however, that clinically significant WM injury may exist that is subthreshold of T2 FLAIR detection and that represents a form of microstructural injury. 6,7,21 DTI-based techniques, which are predicated on the quantification of the randomness of water molecule diffusion, are informative on the microstructural integrity of WM.…”

“…7,27,[29][30][31] Thus, it seems intuitive that WM integrity would influence poststroke recovery. 3,4,[32][33][34][35] The exact mechanisms by which prestroke WM integrity might influence poststroke functional recovery are yet to be determined; however, data that underscore the role of structural connectivity in functional performance in general populations point in the direction of potential underlying pathology. 7,21 Therefore, more severe total pre-AIS burden of WM disease (including overt WMH and microstructural injury in NAWM) may signify a degree of subclinical baseline cognitive and functional decline that predisposes these individuals for less favorable recovery after AIS.…”

“…[3][4][5] However, a growing body of evidence suggests that macrostructural white matter (WM) disease burden, quantified as WMH on T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI, may not adequately reflect the total extent of WM injury and that microstructural injury to normal-appearing WM (NAWM) can be associated with clinical phenotypes. 6,7 We hypothesized that, in patients with AIS, WM microstructural integrity can be assessed globally on diffusion tensor imaging (DTI) of NAWM in the hemisphere contralateral to the AIS (i.e., contralesional NAWM) and that the metrics of diffusivity will demonstrate association with acute ischemic tissue and long-term functional outcomes.…”

Leukoaraiosis Predicts a Poor 90-Day Outcome after Endovascular Stroke Therapy

“…[3][4][5] Yet, leukoaraiosis is frequently encountered in the elderly 6,7 and is well-known to contribute to worse outcomes after acute ischemic stroke. 7,8 Given the expected tripling of the number of persons aged 60 or older in developed nations by 2050 9 and the increasing prevalence of stroke with advancing age, 10,11 it is expected that an increasing number of patients with pre-existing leukoaraiosis will be treated with EST. 12 Accordingly, it is important to understand the potential contribution of leukoaraiosis to functional outcome after EST.…”