Assessment of Brain-Specific and Neuroendocrine Biomarkers for Intracerebral Hemorrhage Diagnosis: A Prospective Cohort Study.

Abstract

Background and purpose: The timing of diagnosis is a critical factor that significantly impacts medical treatment and patient outcomes in individuals with intracerebral hemorrhage (ICH). The study primarily aimed to evaluate the diagnostic potential of four brain-specific biomarkers, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) to differentiate CT-confirmed ICH patients from healthy controls. Secondary aims included comparing results between younger (18-59 years) and older (≥60 years) ICH patients and exploring neuroendocrine hormone levels (adrenocorticotropic hormone [ACTH], agouti-related peptide [AgRP], ciliary neurotrophic factor [CNTF], and growth hormone [GH]) as potential diagnostic tools.

Methods: Serum samples were collected from consecutive adult patients with CT-confirmed ICH diagnoses on days 1 (first 24 hours), 2, 3, 7, and 14 for biomarker analyses in a pilot study. A total of 71 patients and 30 healthy controls were included in the analysis.

Results: Serum concentrations of four brain-specific biomarkers demonstrated significant differentiation between ICH patients and controls at all assessed time points (Days 1, 2, 3, 7, and 14; all p<0.05), with similar significant elevations observed for NfL, tau, and UCH-L1. Day 1 GFAP levels were markedly higher in ICH patients (median 9598 pg/mL compared with healthy controls (39.2 pg/mL; p<0.05). No significant differences were found between young and aged adult ICH subgroups. Neuroendocrine ACTH and AgRP levels were significantly higher in ICH patients compared to controls on both measured time points (Days 1 and 7).

Conclusions: The study's findings suggest that GFAP, NfL, tau, UCH-L1, ACTH, and AgRP exhibit potential as biomarkers for differentiating spontaneous ICH patients from healthy controls. However, given the limitations of the current study design, these findings should be interpreted with caution and cannot be expected to translate directly into clinical practice. Further research is needed to assess these biomarkers' roles in distinguishing stroke types and predicting ICH outcomes.