Leukoaraiosis Predicts Cortical Infarct Volume After Distal Middle Cerebral Artery Occlusion Nils Henninger, MD; Muhib A. Khan, MD; Jiaying Zhang, MD; Majaz Moonis, MD; Richard P. Goddeau Jr, DO Background and Purpose—Leukoaraiosis (LA) predominantly affects the subcortical white matter, but mounting evidence suggests an association with cortical microvascular dysfunction and potentially decreased cortical ischemic tolerance. Thus, we sought to assess whether preexisting LA is predictive of the cortical infarct volume after middle cerebral artery branch occlusion and whether it relates to a worse outcome. Methods—We analyzed data from 117 consecutive patients with middle cerebral artery branch occlusion as documented by admission computed tomography angiography. Baseline clinical, laboratory, and outcome data, as well as final cortical infarct volumes, were retrospectively analyzed from a prospectively collected database. LA severity was assessed on admission computed tomography using the van Swieten scale grading the supratentorial white matter hypoattenuation. Infarct volume predicting a favorable 90-day outcome (modified Rankin Scale score ≤2) was determined by receiver operating characteristic curves. Multivariable linear and logistic regression analyses were used to identify independent predictors of the final infarct volume and outcome. Results—Receiver operating characteristic curve analyses indicated that a final infarct volume of ≤27 mL best predicted a favorable 90-day outcome. Severe LA (odds ratio, 11.231; 95% confidence interval, 2.526–49.926; P=0.001) was independently associated with infarct volume >27 mL. Severe LA (odds ratio, 3.074; 95% confidence interval, 1.055– 8.961; P=0.040) and infarct volume >27 mL (odds ratio, 9.156; 95% confidence interval, 3.191–26.270; P27 mL Hemoglobin A1c Admission glucose, mg/dL Admission creatinine, mg/dL Admission white blood cells, 10³/µL LDL-C within 24 h of admission, mg/dL Triglycerides, mg/dL HDL-C, mg/dL Preadmission medications  Antiplatelets  Warfarin  Statin  Antiglycemic  Antihypertensive Preexisting risk factors  Hypertension  Dyslipidemia  Diabetes mellitus  Prior stroke or transient ischemic attack*  Atrial fibrillation  Coronary artery disease  Congestive heart failure  Peripheral vascular disease  Smoking  Alcohol abuse Final TOAST stroke mechanism  Large-artery atherosclerosis  Cardioembolic  Stroke of other or undetermined cause Leukoaraiosis grade (van Swieten score)  0  1  2  3  4 Pattern of leptomeningeal collaterals  Absent  Less than contralateral hemisphere  Equal to contralateral hemisphere  Greater than contralateral hemisphere  Exuberant Acute intervention  Conservative management  Intravenous rtPA  Endovascular intervention† 90-d mRS, median (IQR)

All Patients (n=117)

None to Moderate LA (VSS ≤2; n=84)

Severe LA (VSS ≥3; n=33)

P Value

67 (±16) 61 (52%) 8 (4–16) 24 (±30) 34 (29%) 6.2 (±1.1) 131 (±49) 1.06 (±0.43) 8.4 (±2.6) 93 (±40) 113 (±74) 46 (±15)

70 (±16) 38 (45%) 6 (4–10) 14 (±18) 13 (38%) 6.4 (±1.2) 132 (±55) 1.05 (±0.44) 8.3 (±2.7) 95 (±43) 120 (±77) 44 (±15)

81 (±9) 23 (70%) 17 (9–21) 49 (±40) 21 (62%) 5.9 (±0.6) 129 (±30) 1.07 (±0.40) 8.5 (±2.4) 89 (±31) 93 (±64) 51 (±13)