Biomarkers in Aneurysmatic and Spontaneous Subarachnoid Haemorrhage: A Clinical Prospective Multicentre Biomarker Panel Study of S100B, Claudin-5, Interleukin-10, TREM-1, TREM-2 and Neurofilament Light Chain As Well As Immunoglobulin G and M

Following aneurysmatic subarachnoid haemorrhage (SAH), complex pathophysiological processes take place which result in ischaemia, dysfunction of the blood-brain barrier and the clinical development of vasospasms and delayed cerebral ischaemia (DCI). The aim of this study was to present a biomarker panel that can be used for temporal assignment in the pathophysiological process after haemorrhage, a prediction of vasospasm, DCI or outcome. In a prospective multicentre approach, complex laboratory chemistry tests were used to determine the value of the biomarkers S100B, Claudin-5, Interleukin (IL) -10, Triggering receptor expresses on myeloid cells (TREM)-1 and TREM-2, and neurofilament light chain (NfL) as well as IgG and IgM in plasma and Cerebro-spinal-fluid (CSF) in SAH patients. The predictive power of mentioned biomarkers with regard to the occurrence of vasospasms, DCI and the outcome (Glasgow Outcome Scale) were defined by using sophisticated statistical methods with the level of significance at p ≤ 0.05. Mean age of the 12 patients included was 56 (SD:14) years with 67% female patients and that of the 11 control subjects was 74 (SD:3) years with 55% female subjects. S100B showed higher concentrations compared to the control patients on the first four days (p ≤ 0.0141). For IL-10, the CSF concentrations showed a continuous increase: day 2 (p = 0.0074), day 4 (p = 0.0012), and day 5 (p < 0.0001). Regarding the TREM1 and TREM2 balance, CSF concentrations of TREM1 increased until day eight (p ≤ 0.0055). TREM-2 plasma concentrations decreased below the levels of control patients and appeared unchanged for the further course. The greatest difference in the CSF concentration of NfL between the patients and the control group was seen on day 8 (p = 0.0104). The differentiation between patients with and without DCI showed different concentration curves of the TREM1 CSF-plasma index with increasing concentrations for patients with DCI. The TREM 2 CSF-plasma index showed higher concentrations for patients with DCI. Patients without DCI showed a decreasing concentration of the NfL CSF-plasma index compared to an increase when vasospasm was detected. NfL, TREM-1 and TREM-2 have the potential to be relevant biomarkers for SAH in the intermediate and delayed injury phase.