Quantitative Pupillometry Predicts Neurologic Deterioration in Patients with Large Middle Cerebral Artery Stroke.

OBJECTIVE

This study assesses whether longitudinal quantitative pupillometry predicts neurological deterioration after large middle cerebral artery (MCA) stroke and determines how early changes are detectable.

METHODS

This prospective, single-center observational cohort study included patients with large MCA stroke admitted to Boston Medical Center's intensive care unit (2019-2024). Associations between time-to-neurologic deterioration and quantitative pupillometry, including Neurological Pupil Index (NPi), were assessed using Cox proportional hazards models with time-dependent covariates adjusted for age, sex, and Alberta Stroke Program Early CT Score. Models using dilation velocity were compared with partial likelihood ratio tests. Pupillometric changes over 2-h intervals in the 12 h preceding deterioration were analyzed with linear mixed-effects modeling and Tukey's test. Matched referents (age, sex, stroke side, follow-up duration) were used for comparison. Optimal thresholds were identified using the Youden Index.

RESULTS

Among 71 patients (mean age 66.5 years; 59.2% women), 32 (45.1%) experienced deterioration. A 1-unit decrease in NPi was associated with a higher hazard of deterioration (hazard ratio 2.46; 95% confidence interval 1.68-3.61). Dilation velocity improved model performance compared to NPi alone. NPi was significantly lower at 0-2 h (3.81 vs. 4.38, p = 0.001) and 2-4 h (3.71 vs. 4.38, p < 0.001) before deterioration compared to 10-12 h prior. Optimal thresholds were 4.01 for NPi, 0.49 mm/s for dilation velocity, and -0.15 change in NPi over 12 h.

INTERPRETATION: Quantitative pupillometry predicts neurological deterioration in MCA stroke, with declines detectable up to 12 h prior. Dilation velocity shows promise as a novel biomarker. ANN NEUROL 2025;97:930-941.