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NEUROLOGY 2009;72:1403-1410
© 2009 American Academy of Neurology

Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke

E. M. Arsava, MD, R. Rahman, PhD, J. Rosand, MD, MSc, J. Lu, MD, E. E. Smith, MD, N. S. Rost, MD, A. B. Singhal, MD, M. H. Lev, MD, K. L. Furie, MD, W. J. Koroshetz, MD, A. G. Sorensen, MD and H. Ay, MD

From AA Martinos Center for Biomedical Imaging, Department of Radiology (E.M.A., J.L., M.H.L., A.G.S., H.A.), and Stroke Service, Department of Neurology (R.R., J.R., E.E.S., N.S.R., A.B.S., K.L.F., H.A.) and Center for Human Genetic Research (R.R., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Program in Medical and Population Genetics (R.R., J.R., N.S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; and National Institute of Neurological Disorders and Stroke (W.J.K.), NIH, Bethesda, MD.

Address correspondence and reprint requests to Dr. Hakan Ay, AA Martinos Center for Biomedical Imaging and Stroke Service, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2301, Charlestown, MA 02129 hay{at}partners.org

Background: Leukoaraiosis (LA) is closely associated with aging, a major determinant of clinical outcome after ischemic stroke. In this study we sought to identify whether LA, independent of advancing age, affects outcome after acute ischemic stroke.

Methods: LA volume was quantified in 240 patients with ischemic stroke and MRI within 24 hours of symptom onset. We explored the relationship between LA volume at admission and clinical outcome at 6 months, as assessed by the modified Rankin Scale (mRS). An ordinal logistic regression model was developed to analyze the independent effect of LA volume on clinical outcome.

Results: Bivariate analyses showed a significant correlation between LA volume and mRS at 6 months (r = 0.19, p = 0.003). Mean mRS was 1.7 ± 1.8 among those in the lowest (≤1.2 mL) and 2.5 ± 1.9 in the highest (>9.9 mL) quartiles of LA volume (p = 0.01). The unfavorable prognostic effect of LA volume on clinical outcome was retained in the multivariable model (p = 0.002), which included age, gender, stroke risk factors (hypertension, diabetes mellitus, atrial fibrillation), previous history of brain infarction, admission plasma glucose level, admission NIH Stroke Scale score, IV rtPA treatment, and acute infarct volume on MRI as covariates.

Conclusions: The volume of leukoaraiosis is a predictor of clinical outcome after ischemic stroke and this relationship persists after adjustment for important prognostic factors including age, initial stroke severity, and infarct volume.

Abbreviations: CCS = Causative Classification of Stroke; CE = cardioaortic embolism; CI = confidence interval; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; IQR = interquartile range; LA = leukoaraiosis; LAA = large artery atherosclerosis; mRS = modified Rankin Scale; NIHSS = National Institute of Health Stroke Scale; OR = odds ratio; rtPA = recombinant tissue plasminogen activator; SAO = small artery occlusion; STOPStroke = Screening Technology and Outcome Project in Stroke Study; UND/UNC = undetermined/unclassified.

*These authors contributed equally and share first authorship.

Supported by NIH grants R01-NS059727 (J.R.), R01-NS051412 and P50-NS051343 (A.B.S.), P50-NS051343 (M.H.L.), R01-HS011392 and P50-NS051343 (K.L.F.), and R01-NS038477 (A.G.S.).

Disclosure: M.H.L.: GE Medical Services—research support, advisory board, and speaker fees; Bracco Diagnostics—advisory board and speaker fees; Coaxia—advisory board; K.L.F.: consultant for GE Healthcare; A.G.S.: full disclosures are listed in http://www.biomarkers.org/NewFiles/disclosures.html.

Received October 6, 2008. Accepted in final form January 20, 2009.






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