Quantification and prospective evaluation of serum NfL and GFAP as blood-derived biomarkers of outcome in acute ischemic stroke patients

Abstract

Identification of reliable and accessible biomarkers to characterize ischemic stroke patients’ prognosis remains a clinical challenge. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are markers of brain injury, detectable in blood by high-sensitive technologies. Our aim was to measure serum NfL and GFAP after stroke, and to evaluate their correlation with functional outcome and the scores in rehabilitation scales at 3-month follow-up. Stroke patients were prospectively enrolled in a longitudinal observational study within 24 hours from symptom onset (D1) and monitored after 7 (D7), 30 ± 3 (M1) and 90 ± 5 (M3) days. At each time-point serum NfL and GFAP levels were measured by Single Molecule Array and correlated with National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), Trunk Control Test (TCT), Functional Ambulation Classification (FAC) and Functional Independence Measure (FIM) scores. Serum NfL and GFAP showed different temporal profiles: NfL increased after stroke with a peak value at D7; GFAP showed an earlier peak at D1. NfL and GFAP concentrations correlated with clinical/rehabilitation outcomes both longitudinally and prospectively. Multivariate analysis revealed that NfL-D7 and GFAP-D1 were independent predictors of 3-month NIHSS, TCT, FAC and FIM scores, with NfL being the biomarker with the best predictive performance.

Blood-based protein biomarkers during the acute ischemic stroke treatment window: a systematic review

“…Six studies compared AIS patients with patients who experienced stroke albeit two studies investigated both healthy controls and stroke mimics. Half of the studies showed higher GFAP levels in AIS patients compared to controls ( p ≤ 0.05) ( 81 , 85 , 86 ). One study showed higher levels of GFAP in AIS patients compared to HC but statistical testing for differences was not performed (195.22 pg./mL, range: 52.77–1526.74 vs. 80.37 pg/mL, range: 56.43–132.86) ( 57 ).…”

Dynamic Changes and Clinical Significance of Plasma Galectin-3 in Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy

“…However, many biomarkers are often time dependent. Even if biomarkers related to AIS, such as Galectin-3, MMP-9, 31 NSE, 32 GFAP, 33 IncRNA H19, 34 and FSAP, 35 are identified, larger and more diverse samples are needed for repeated measurements at multiple time points to assess their clinical value.…”

GFAP as Astrocyte-Derived Extracellular Vesicle Cargo in Acute Ischemic Stroke Patients—A Pilot Study

“…After vessel occlusion, the gradual occurrence of astrocyte damage and BBB disintegration (usually not before 6 to 12 h after stroke onset) leads to a delayed release of GFAP into the plasma, not reaching peak concentrations before 48–96 h after symptoms onset [ 18 , 79 , 80 , 81 , 82 ]. However, a recent study related an earlier peak of GFAP at 24 h [ 83 ]. Wunderlich et al reported that serum GFAP concentrations remain increased at a lower level for at least 5 days after stroke onset [ 79 ].…”

“…Furthermore, GFAP concentrations in CSF (mean 8.7 h after stroke onset) [ 89 ] and serum (from 72 h on, with the highest correlation at 96 h after stroke onset) [ 79 ] correlate with IS long-term outcomes according to the mRS score at three months after the stroke onset. Similarly, an association was revealed between serum levels of GFAP and stroke patients’ independence in daily living activities over a three-month follow-up, measured through specific motor and disability scores on rehabilitation scales (trunk control test, functional ambulation classification, and functional independence measure scores) [ 83 ]. Elevated serum GFAP within 24 h predicts poor functional outcomes independently at one-year post-stroke follow-up [ 35 ].…”