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. 2024 Sep;9(3):751-762.
doi: 10.1177/23969873241234436. Epub 2024 Feb 24.

Incremental value of serum neurofilament light chain and glial fibrillary acidic protein as blood-based biomarkers for predicting functional outcome in severe acute ischemic stroke

Christoph Vollmuth  1 , Cornelia Fiessler  2 , Felipe A Montellano  1   2 , Alexander M Kollikowski  3 , Fabian Essig  1 , Patrick Oeckl  4   5 , Lorenzo Barba  6 , Petra Steinacker  6 , Cara Schulz  1 , Kathrin Ungethüm  2 , Judith Wolf  1 , Mirko Pham  3 , Michael K Schuhmann  1 , Peter U Heuschmann  2   7   8 , Karl Georg Haeusler  1 , Guido Stoll  1 , Markus Otto  6 , Hermann Neugebauer  1
Affiliations

Incremental value of serum neurofilament light chain and glial fibrillary acidic protein as blood-based biomarkers for predicting functional outcome in severe acute ischemic stroke

Christoph Vollmuth et al. Eur Stroke J. 2024 Sep.

Abstract

Introduction: Blood-based biomarkers may improve prediction of functional outcome in patients with acute ischemic stroke. The role of neurofilament light chain (NfL) and glial fibrillary acidic (GFAP) as potential biomarkers especially in severe stroke patients is unknown.

Patients and methods: Prospective, monocenter, cohort study including consecutive patients with severe ischemic stroke in the anterior circulation on admission (NIHSS score ⩾ 6 points or indication for mechanical thrombectomy). Outcome was assessed 3 months after the index stroke by the modified Rankin Scale (mRS). Serum biomarkers levels of NfL and GFAP were determined by ultrasensitive ELISA. Univariate and multivariate logistic regression models were performed to determine the association of biomarker levels and functional disability. Discrimination, calibration, and overall performance were analyzed in different models via AUROC, calibration plots (with Emax and Eavg), Brier-score and R2 using variables, identified as important covariates for functional outcome in previous studies.

Results: Between 06/2020 and 08/2021, 213 patients were included [47% female, mean age 76 (SD ± 12) years, median NIHSS score 13 (interquartile range, IQR 9; 17)]. Biomarker serum levels were measured at a median of 1 [IQR, 1; 2] day after admission. Compared to patients with mRS 0-2 at 3 months, patients with mRS 3-6 had higher serum levels of NfL (median: 136 pg/ml vs 41 pg/ml; p < 0.0001) and GFAP (700 ng/ml vs 9.6 ng/ml; p < 0.0001). Both biomarkers were significantly associated with functional outcome [adjusted logistic regression, odds ratio (95% CI) for NfL: 2.63 (1.62; 4.56), GFAP: 2.16 (1.58; 3.09)]. In all models the addition of serum NfL led to a significant improvement in the AUROC, as did the addition of serum GFAP. Calibration plots showed high agreement between the predicted and observed outcomes and after addition of the two blood-based biomarkers there was an improvement of the overall performance.

Conclusion: Prediction of functional outcome after severe acute ischemic stroke was improved by the blood-based biomarkers serum NfL and GFAP, measured in the acute phase of stroke. These findings have to be replicated in independent external cohorts.Study registration: DRKS00022064.

Keywords: Blood-based biomarkers; GFAP; NfL; ischemic stroke; prediction; prognosis.

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Conflict of interest statement

Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KGH reports speaker’s honoraria, consulting fees, lecture honoraria and/or study grants from Abbott, Alexion, Amarin, AstraZeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Medronic, Novartis, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, and W.L. Gore and Associates. PUH reports grants from German Ministry of Research and Education, German Research Foundation, European Union, Federal Joint Committee (G-BA) within the Innovationfond, Charité–Universitätsmedizin Berlin, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, University Göttingen (within FIND-AF [A Prospective, Randomised, Controlled Study to Determine the Detection of Atrial Fibrillation by Prolonged and Enhanced Holter Monitoring as Compared to Usual Care in Stroke Patients] randomized, supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), University Hospital Heidelberg (within Registry of Acute Stroke Under Novel Oral Anticoagulants [RASUNOA]-prime, supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo), grants from Charité–Universitätsmedizin Berlin (within Mondafis, supported by an unrestricted research grant to the Charité from Bayer), outside the submitted work. MO served as scientific advisor for Axon, Biogen, Roche and Fujirebio. All other authors have nothing to declare.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Final study population selection process.
Figure 2.
Figure 2.
Serum biomarkers in patients with ischemic stroke. (a) Serum biomarkers according to 3-months mRS (mRS 0–2 vs mRS 3–6). (b) Serum biomarkers according the mRS at discharge (mRS 0–2 vs mRS 3–6). (c) Mortality at follow-up 3 months after index stroke. (d) mRS according to median biomarker levels (NfL: 96 pg/ml; GFAP: 5.7 ng/ml). (e) ROC-curve good versus poor outcome 3 months after index stroke. (f) Spearman’s correlations among biomarkers serum NfL ~ serum GFAP. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.
Figure 3.
Figure 3.
Calibration plots for model A and model B: Model A: mRS ~ age + NIHSS on admission. A1) (without biomarker). A2) + NfL. A3) + GFAP. Model B: mRS ~ age + NIHSS on admission + ASPECTS on admission (8–10 vs 0–7) + mechanical recanalization (yes/no). B1) (without biomarker). B2) + NfL. B3) + GFAP.
See this image and copyright information in PMC

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