Abstract
OBJECTIVE: To determine the association of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) with the development of a malignant infarction in severe anterior circulation ischemic stroke. METHODS: In this prospective, single-center cohort study, patients with severe acute ischemic stroke due to large vessel occlusion (LVO) in the anterior circulation were included. Malignant infarction was defined by clinical and neuroradiological parameters. Serum biomarkers levels of NfL and GFAP were determined by ultrasensitive ELISA. Univariable and multivariable logistic regression models, along with receiver operating characteristics (ROC) characteristic analyses, were performed to assess the predictive value of sNfL and sGFAP. RESULTS: Between 06/2020 and 09/2022, 383 patients were included [54.6% female, median age 79 (interquartile range, (IQR) 69-84) years, median NIHSS Score on admission 14 (IQR 9-17)]. Biomarker serum levels were measured at a median of 36 [IQR 23-61] hours after symptom onset. Malignant infarction occurred in 83 patients (21.7%). Both sNfL and sGFAP levels were significantly elevated in patients with compared to those without malignant infarction (sNfL: 208 pg/ml vs. 96 pg/ml, p < 0.001; sGFAP: 36.6 ng/ml vs. 4.1 ng/ml, p < 0.001). After adjusting for clinical and radiological parameters, sNfL and sGFAP remained independent predictors for malignant infarction (sNfL: OR 2.91 [1.55-5.45], p < 0.001; sGFAP: 3.49 [1.80-6.75], p < 0.001). The inclusion of both biomarkers in prediction models significantly improved their predictive value. CONCLUSIONS: Serum NfL and GFAP independently predict malignant infarction in severe anterior circulation ischemic stroke, albeit with only a low effect size in models with established prognostic factors. Further studies investigating earlier and serial biomarker measurement are required to improve prognostic models supporting risk stratification and decision making. STUDY REGISTRATION: DRKS00022064.In severe anterior circulation ischemic stroke due to LVO, sNfL and sGFAP levels were significantly elevated in patients who developed malignant infarction. Both biomarkers independently predicted malignant infarction after adjustment for clinical and radiological factors. Nevertheless, the additional predictive value beyond established prognostic parameters was modest.