Circulating brain injury biomarkers increase after endoscopic surgery for pituitary tumors

Tobias Hallén,Daniel S Olsson,Casper Hammarstrand,Dan Farahmand,Ann-Charlotte Olofsson,Eva Jakobsson Ung,Sofie Jakobsson,Henrik Bergquist,Kaj Blennow,Henrik Zetterberg,Gudmundur Johannsson,Thomas Skoglund

doi:10.1016/j.jocn.2021.04.030

Abstract

Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS.

Highlights

Pituitary tumors account for approximately 15–20% of intracranial tumors [1,2]
The data was derived from the Gothenburg Pituitary Tumor (GoPT) study, a prospective study that is enrolling patients scheduled for pituitary surgery at Sahlgrenska University Hospital, which is the sole provider of neurosurgical services for 1.8 million people in the western region of Sweden
No correlations were found between the change in total MFI-20 score and the increase in glial fibrillary acidic protein (GFAP) at day 1 or with the increase in neurofilament light (NFL) at day 5 (Fig. 4). In this prospective exploratory study, we found that the plasma concentration of circulating brain injury biomarkers increased in patients who underwent endoscopic transsphenoidal surgery for pituitary tumors

Summary

Introduction

Pituitary tumors account for approximately 15–20% of intracranial tumors [1,2]. The majority of pituitary tumors are benign ade-⇑ Corresponding author at: Department of Neurosurgery, Sahlgrenska University nomas [3]. Pituitary tumors account for approximately 15–20% of intracranial tumors [1,2]. The majority of pituitary tumors are benign ade-. ⇑ Corresponding author at: Department of Neurosurgery, Sahlgrenska University nomas [3]. Pituitary tumors are usually histologically benign, they can cause severe symptoms due to multiple endocrine deficiencies or compression of adjacent sensitive structures such as the optic chiasm, the hypothalamus, and the frontal lobes, causing long-term neurological and cognitive consequences [3,6,7]. Patients with pituitary tumors have been reported to have excess morbidity and mortality [8,9].

Methods

Results

Discussion

Conclusion