Journal Article

DZNE-2024-00257

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.

Vollmuth, C. ; Fiessler, C. ; Montellano, F. A. ; Kollikowski, A. M. ; Essig, F. ; Oeckl, P.DZNE* ; Barba, L. ; Steinacker, P. ; Schulz, C. ; Ungethüm, K. ; Wolf, J. ; Pham, M. ; Schuhmann, M. K. ; Heuschmann, P. U. ; Haeusler, K. G. ; Stoll, G. ; Otto, M. ; Neugebauer, H.

2024
Sage Publishing London

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Please use a persistent id in citations: doi:10.1177/23969873241234436

Abstract: 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.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.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.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.

Keyword(s): Humans (MeSH) ; Glial Fibrillary Acidic Protein: blood (MeSH) ; Female (MeSH) ; Male (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Biomarkers: blood (MeSH) ; Aged (MeSH) ; Ischemic Stroke: blood (MeSH) ; Ischemic Stroke: diagnosis (MeSH) ; Ischemic Stroke: therapy (MeSH) ; Prospective Studies (MeSH) ; Aged, 80 and over (MeSH) ; Middle Aged (MeSH) ; Prognosis (MeSH) ; Severity of Illness Index (MeSH) ; Blood-based biomarkers ; GFAP ; NfL ; ischemic stroke ; prediction ; prognosis

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Contributing Institute(s):

1. Translational Mass Spectrometry and Biomarker Research (AG Öckl)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 5 ; JCR ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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