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Background: Genetic association studies can reveal biology and treatment targets but have received limited attention for stroke recovery. STRONG (Stroke, Stress, Rehabilitation, and Genetics) was a prospective, longitudinal (1-year), genetic study in adults with stroke at 28 US stroke centers. The primary aim was to examine the association that candidate genetic variants have with (1) motor/functional outcomes and (2) stress-related outcomes., Methods: For motor/functional end points, 3 candidate gene variants (ApoE ε4, BDNF [brain-derived neurotrophic factor], and a dopamine polygenic score) were analyzed for associations with change in grip strength (3 months-baseline), function (3-month Stroke Impact Scale-Activities of Daily Living), mood (3-month Patient Health Questionnaire-8), and cognition (12-month telephone-Montreal Cognitive Assessment). For stress-related outcomes, 7 variants (serotonin transporter gene-linked promoter region, ACE [angiotensin-converting enzyme], oxytocin receptor, FKBP5 [FKBP prolyl isomerase 5], FAAH [fatty acid amide hydrolase], BDNF, and COMT [catechol-O-methyltransferase]) were assessed for associations with posttraumatic stress disorder ([PTSD]; PTSD Primary Care Scale) and depression (Patient Health Questionnaire-8) at 6 and 12 months; stress-related genes were examined as a function of poststroke stress level. Statistical models (linear, negative binomial, or Poisson regression) were based on response variable distribution; all included stroke severity, age, sex, and ancestry as covariates. Stroke subtype was explored secondarily. Data were Holm-Bonferroni corrected. A secondary replication analysis tested whether the rs1842681 polymorphism (identified in the GISCOME study [Genetics of Ischaemic Stroke Functional Outcome]) was related to 3-month modified Rankin Scale score in STRONG., Results: The 763 enrollees were 63.1±14.9 (mean±SD) years of age, with a median initial National Institutes of Health Stroke Scale score of 4 (interquartile range, 2-9); outcome data were available in n=515 at 3 months, n=500 at 6 months, and n=489 at 12 months. At 1 year poststroke, the rs6265 (BDNF) variant was associated with poorer cognition (0.9-point lower telephone-Montreal Cognitive Assessment score, P =1×10 -5 ). For stress-related outcomes, rs4291 (ACE) and rs324420 (FAAH) were risk factors linking increased poststroke stress with higher 1-year depression and PTSD symptoms ( P <0.05), while rs4680 (COMT) linked poststroke stress with lower 1-year depression and PTSD. Findings were unchanged when considering stroke subtype. STRONG replicated GISCOME: rs1842681 was associated with lower 3-month modified Rankin Scale score ( P =3.2×10 -5 )., Conclusions: This study identified genetic associations with cognitive function, depression, and PTSD 1 year poststroke. Genetic susceptibility to PTSD and depressive symptoms varied according to the amount of poststroke stress, underscoring the critical role of lived experiences in recovery. Together, the results suggest that genetic association studies provide insights into the biology of stroke recovery in humans., Competing Interests: Dr Cramer serves as a consultant for Constant Therapeutics, BrainQ, Myomo, MicroTransponder, Panaxium, Beren Therapeutics, Medtronic, Stream Biomedical, NeuroTrauma Sciences, and TRCare. Dr Rosand receives research support from the National Institutes of Health (NIH) and the American Heart Association. He receives consulting fees from the National Football League (NFL) and Eli Lilly; compensation from Elsevier Publishing for other services; and employment by Broad Institute of MIT and Harvard University. Dr Silver reports ownership of Magnapeutics, LLC; medicolegal expert review; Steering Committee for the Women’s Health Initiative; and consultant to Teladoc Health, Inc. Dr Griessenauer serves as a consultant for Medtronic, Stryker, Penumbra, and MicroVention. Dr Majersik is an Associate Editor at Stroke, editorial board member at Journal of Stroke and Cerebrovascular Disease, consultant at Woolsey Pharmaceuticals, provides peer review for UpToDate, and is funded by NIH/National Institute of Neurological Disorders and Stroke and NIH/National Center for Advancing Translational Sciences. Dr Braun reports grants from Eunice Kennedy Shriver National Institute of Child Health and Human Development. The other authors report no conflicts.

Background and Purpose: Clinical methods have incomplete diagnostic value for early diagnosis of acute stroke and large vessel occlusion (LVO). Electroencephalography is rapidly sensitive to brain ischemia. This study examined the diagnostic utility of electroencephalography for acute stroke/transient ischemic attack (TIA) and for LVO., Methods: Patients (n=100) with suspected acute stroke in an emergency department underwent clinical exam then electroencephalography using a dry-electrode system. Four models classified patients, first as acute stroke/TIA or not, then as acute stroke with LVO or not: (1) clinical data, (2) electroencephalography data, (3) clinical+electroencephalography data using logistic regression, and (4) clinical+electroencephalography data using a deep learning neural network. Each model used a training set of 60 randomly selected patients, then was validated in an independent cohort of 40 new patients., Results: Of 100 patients, 63 had a stroke (43 ischemic/7 hemorrhagic) or TIA (13). For classifying patients as stroke/TIA or not, the clinical data model had area under the curve=62.3, whereas clinical+electroencephalography using deep learning neural network model had area under the curve=87.8. Results were comparable for classifying patients as stroke with LVO or not., Conclusions: Adding electroencephalography data to clinical measures improves diagnosis of acute stroke/TIA and of acute stroke with LVO. Rapid acquisition of dry-lead electroencephalography is feasible in the emergency department and merits prehospital evaluation.