Early plasma biomarker dynamic profiles are associated with acute ischemic stroke outcomes

Background Early outcome prediction after acute ischemic stroke (AIS) might be improved with blood‐based biomarkers. We investigated whether the longitudinal profile of a multi‐marker panel could predict the outcome of successfully recanalized AIS patients. Methods We used ultrasensitive single‐mole...

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Published inEuropean journal of neurology Vol. 29; no. 6; pp. 1630 - 1642
Main Authors Correia, Manuel, Silva, Isabel, Gabriel, Denis, Simrén, Joel, Carneiro, Angelo, Ribeiro, Sara, Dória, Hugo Mota, Varela, Ricardo, Aires, Ana, Minta, Karolina, Antunes, Rui, Felgueiras, Rui, Castro, Pedro, Blenow, Kaj, Magalhães, Rui, Zetterberg, Henrik, Maia, Luis F.
Format Journal Article
LanguageEnglish
Published England John Wiley & Sons, Inc 01.06.2022
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Summary:Background Early outcome prediction after acute ischemic stroke (AIS) might be improved with blood‐based biomarkers. We investigated whether the longitudinal profile of a multi‐marker panel could predict the outcome of successfully recanalized AIS patients. Methods We used ultrasensitive single‐molecule array (Simoa) to measure glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total‐tau (t‐tau) and ELISA for brevican in a prospective study of AIS patients with anterior circulation large vessel occlusion successfully submitted to thrombectomy. Plasma was obtained at admission, upon treatment, 24 h and 72 h after treatment. Clinical and neuroimaging outcomes were assessed independently. Results Thirty‐five patients (64.8%) had good early clinical or neuroimaging outcome. Baseline biomarker levels did not distinguish between outcomes. However, longitudinal intra‐individual biomarker changes followed different dynamic profiles with time and according to outcome. GFAP levels exhibited an early and prominent increase between admission and just after treatment. NfL increase was less pronounced between admission and up to 24 h. T‐tau increased between treatment and 24 h. Interestingly, GFAP rate‐of‐change (pg/ml/h) between admission and immediately after recanalization had a good discriminative capacity between clinical outcomes (AUC = 0.88, p < 0.001), which was higher than admission CT‐ASPECTS (AUC = 0.75, p < 0.01). T‐tau rate‐of‐change provided moderate discriminative capacity (AUC = 0.71, p < 0.05). Moreover, in AIS patients with admission CT‐ASPECTS <9 both GFAP and NfL rate‐of‐change were good outcome predictors (AUC = 0.82 and 0.77, p < 0.05). Conclusion Early GFAP, t‐tau and NfL rate‐of‐change in plasma can predict AIS clinical and neuroimaging outcome after successful recanalization. Such dynamic measures match and anticipate neuroimaging predictive capacity, potentially improving AIS patient stratification for treatment, and targeting individualized stroke care. Longitudinal biomarker panel profile in the acute phase of stroke patient care.
Bibliography:Funding information
Manuel Correia and Isabel Silva shared first co‐authorship.
This work was financed by FEDER ‐ Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 ‐ Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI‐01‐0145‐FEDER‐031674 (PTDC/MEC‐NEU/31674/2017) and by FEDER ‐ Fundo Europeu de Desenvolvimento Regional through the COMPETE 2020 ‐ Operacional Programme for Competitiveness and Internationalization (POCI) funds to the call NORTE2020 17/SI/2019 ‐ Sistema De Incentivos À Investigação E Desenvolvimento Tecnológico, within the scopus of the project No. 47043. H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018‐02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG‐720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809‐2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF‐21‐831376‐C, #ADSF‐21‐831381‐C and #ADSF‐21‐831377‐C), the Olav Thon Foundation, the Erling‐Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019‐0228), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No. 860197 (MIRIADE), and the UK Dementia Research Institute at UCL. K.B. is supported by the Swedish Research Council (#2017‐00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB‐201809‐2016615), the Swedish Alzheimer Foundation (#AF‐742881), Hjärnfonden, Sweden (#FO2017‐0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF‐agreement (#ALFGBG‐715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019‐466‐236) and the National Institutes of Health (NIH), USA (grant #1R01AG068398‐01). The funding agencies had no role in study design, data collection and analysis, decision to publish, or manuscript preparation.
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ISSN:1351-5101
1468-1331
DOI:10.1111/ene.15273