Plasma Brain-Derived Tau in Prognosis of Large Vessel Occlusion Ischemic Stroke

Author:

Varela Ricardo1ORCID,Gonzalez-Ortiz Fernando23ORCID,Dias Alexandre45ORCID,Knuth Nicoló Luca6ORCID,Fonte Joana1ORCID,Pinto Beatriz1,Yuksekel Idil13ORCID,Abreu Vasco1,Silva Isabel45ORCID,Igreja Liliana1,Lopes Joana1,Silva José1,Dias Rafael7ORCID,Filipe João Pedro1ORCID,Malaquias Maria João1,Moutinho Ana45ORCID,Gabriel Denis1ORCID,Aires Ana7ORCID,Antunes Rui1,Rocha José Pedro1,Felgueiras Rui1,Almendra Ricardo8ORCID,Castro Pedro7,Zetterberg Henrik1391011,Magalhães Rui5,Karikari Thomas K.112ORCID,Correia Manuel15ORCID,Blennow Kaj13ORCID,Maia Luís F.145ORCID

Affiliation:

1. Neuroscience Department, Centro Hospitalar Universitário de Santo António, Porto, Portugal (R.V., J.F., B.P., V.A., L.I., J.L., J.S., J.P.F., M.J.M., D.G., R. Antunes, J.P.R., R.F., M.C., L.F.M.).

2. Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden (F.G.-O., I.Y., H.Z., T.K.K., K.B.).

3. Sahlgrenska University Hospital, Mölndal, Sweden (F.G.-O., I.Y., H.Z., K.B.).

4. i3S–Instituto de Investigação e Inovação em Saúde (A.D., I.S., A.M., L.F.M.), Universidade do Porto, Portugal.

5. Instituto de Ciências Biomédicas Abel Salazar (A.D., I.S., A.M., R.M., M.C., L.F.M.), Universidade do Porto, Portugal.

6. Institute for Stroke and Dementia Research, LMU University Hospital, LMU Munich, Germany (N.L.K.).

7. Neurology Department, Centro Hospitalar Universitário de São João, Porto, Portugal (R.D., A.A., P.C.).

8. Neurology Department, Centro Hospitalar de Trás-os-Montes e Alto-Douro, Vila Real, Portugal (R. Almendra).

9. UCL Institute of Neurology, London, United Kingdom (H.Z.).

10. UK Dementia Research Institute at UCL, London, United Kingdom (H.Z.).

11. Hong Kong Center of Neurodegenerative Diseases, Clear Water Bay, China (H.Z.).

12. University of Pittsburgh, PA (T.K.K.).

Abstract

BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65–0.87]; P <0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82–0.97]; P <0.001). The score’s predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71–0.92]; P <0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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