{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:08:16Z","timestamp":1781276896022,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T00:00:00Z","timestamp":1737158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23NS11603"],"award-info":[{"award-number":["K23NS11603"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study assesses whether longitudinal quantitative pupillometry predicts neurological deterioration after large middle cerebral artery (MCA) stroke and determines how early changes are detectable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This prospective, single\u2010center observational cohort study included patients with large MCA stroke admitted to Boston Medical Center's intensive care unit (2019\u20132024). Associations between time\u2010to\u2010neurologic deterioration and quantitative pupillometry, including Neurological Pupil Index (NPi), were assessed using Cox proportional hazards models with time\u2010dependent 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\u2010h intervals in the 12\u2009h preceding deterioration were analyzed with linear mixed\u2010effects modeling and Tukey's test. Matched referents (age, sex, stroke side, follow\u2010up duration) were used for comparison. Optimal thresholds were identified using the Youden Index.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 71 patients (mean age 66.5\u2009years; 59.2% women), 32 (45.1%) experienced deterioration. A 1\u2010unit decrease in NPi was associated with a higher hazard of deterioration (hazard ratio 2.46; 95% confidence interval 1.68\u20133.61). Dilation velocity improved model performance compared to NPi alone. NPi was significantly lower at 0\u20132\u2009h (3.81 vs. 4.38, p\u2009=\u20090.001) and 2\u20134\u2009h (3.71 vs. 4.38, p\u2009&lt;\u20090.001) before deterioration compared to 10\u201312\u2009h prior. Optimal thresholds were 4.01 for NPi, 0.49\u2009mm\/s for dilation velocity, and\u2009\u22120.15 change in NPi over 12\u2009h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Quantitative pupillometry predicts neurological deterioration in MCA stroke, with declines detectable up to 12\u2009h prior. Dilation velocity shows promise as a novel biomarker. 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