Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke

Background and Purpose The National Institutes of Health Stroke Scale (NIHSS) provides a reliable, quantitative measure of ischemic stroke severity and is predicted by the infarct size. We sought to determine whether leukoaraiosis severity affects the association between infarct size and NIHSS. Methods NIHSS and diffusion-weighted imaging-defined infarct volumes from 312 prospectively enrolled patients with supratentorial, ischemic strokes were analyzed. Leukoaraiosis severity was graded according to the Fazekas scale and conceptually defined as absent (0; n=44), mild (1-2; n=106), moderate (3-4; n=105), and severe (5-6; n=57). ANCOVA was used to describe the effect of leukoaraiosis on the association between infarct volume and NIHSS. Multivariable linear regression models were constructed to assess whether the association of leukoaraiosis and infarct volume on NIHSS was independent of other clinically relevant covariates. Results Overall, there was a significant correlation between the infarct volume and NIHSS (r=0.591; P<0.001). This correlation significantly attenuated with increasing leukoaraiosis severity from r=0.786 (P<0.001; absent leukoaraiosis) to r=0.498 (P<0.001; severe leukoaraiosis) and as shown by ANCOVA (P<0.001). Leukoaraiosis (coefficient, 0.107; 95% confidence interval, 0.036-0.179; P=0.016) and infarct volume (coefficient, 0.360; 95% confidence interval, 0.305-0.416; P<0.001) were independently associated with a greater NIHSS deficit in the fully adjusted multivariable model. Conclusions Leukoaraiosis significantly modulates the association between infarct volume and NIHSS. The clinical implications of these findings need further exploration in prospective studies but may be relevant to mitigate outcome differences in patients with stroke by aiding treatment decisions that rely on the NIHSS.