Neglect performance in acute stroke is related to severity of white matter hyperintensities

Background: Leukoaraiosis and its progression have longitudinally been associated with cognitive decline and dementia. Its role in acute cognitive function and response to acute cerebral ischemia is less well understood. We evaluated whether the presence and extent of leukoaraiosis, or white matter hyperintensities (WMH), had an impact on performance on tests of hemispatial neglect in acute ischemic stroke patients. Methods: A series of 206 acute ischemic right-hemispheric stroke patients at Johns Hopkins Hospital underwent brain MRI and cognitive assessment for hemispatial neglect within 5 days of symptom onset. Error rates on neglect tests were evaluated, as were dichotomized measures of neglect, including 'any', 'severe' or 'worst' neglect, based on Z scores of at least 2 on 1, 2 or 3 tests (respectively) within a neglect battery. Acute infarct volumes were measured on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery images were reviewed for WMH, using the Cardiovascular Health Study (CHS) rating scale (ranging from 0 to 9, with 9 being 'most extensive'). Linear regression was used to evaluate 'error rate on neglect test' as the dependent variable, as a measure of neglect severity, with 'WMH category' as the primary independent variable, including adjustment for age, sex, race and infarct volume (on DWI). Logistic regression was used to evaluate a binary definition of neglect (defined as above) relative to the same independent variable and covariates. Results: Each 1-point increase in CHS leukoaraiosis category was associated with 1.20-fold increased odds (95% CI: 1.00-1.43) of having any neglect, 1.23-fold increased odds (95% CI: 1.02-1.49) of having severe neglect and 1.33-fold increased odds of having worst neglect (95% CI: 1.01-1.76) after adjusting for infarct volume, age, sex and race. Increasing age and infarct size were also important predictors of neglect severity, with a 2.36% higher error rate (95% CI: 0.75-3.97%) on the line cancellation test associated with each category increase in CHS score; similar results were found for each of the neglect tests. Line cancellation neglect scores were worse in individuals with both severe WMH and large infarcts (p interaction, unadjusted = 0.03). Conclusions: More severe leukoaraiosis is associated with more hemispatial neglect after acute ischemic stroke, independent of infarct volume, age and sex. We found not only more frequent neglect but also more severe neglect, based on error rates on neglect tests, in individuals with increasing leukoaraiosis. This emphasizes the importance of preexisting brain microvascular disease in outcomes of stroke patients. Further studies of the possible mechanism behind this association are needed.