Xiaoyu Wu,1 Heng He,1 Dapu Shen,1 Xiaohui Ye,2 Ziyin Chen,3,4 Shengdong Zou,3,4 Kechen Zhou,5 Xiufeng Ye,6 Zhixing Zhang,7 Huguang Li,1 Jin Liu1 

1Department of Neurosurgery, Lishui Hospital of Wenzhou Medical University, Lishui City People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 2Department of Nursing, Lishui Hospital of Wenzhou Medical University, Lishui City People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China; 5Jiangxi Medical College, Nanchang University, Nangchang, Jiangxi Province, People’s Republic of China; 6Department of Neurosurgery, Longquan City People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 7Department of Neurosurgery, Jinyun County Hospital of Traditional Chinese Medicine, Lishui, Zhejiang Province, People’s Republic of China

Correspondence: Jin Liu, Department of Neurosurgery, Lishui Hospital of Wenzhou Medical University, Lishui City People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China, Email liujin-614@163.com

Background: NADPH oxidase 4 (NOX4) may play a critical role for inducing oxidative stress and inflammation after spontaneous intracerebral hemorrhage (sICH). This study was performed to assess associations of serum NOX4 levels with sICH severity, early neurological deterioration (END) and neurological outcomes.
Methods: In this prospective cohort study, serum of 161 sICH patients and 161 controls were collected for quantifying NOX4 levels. END was defined as a decrease of ≥ 2 points in Glasgow coma scale (GCS) score within 24 hours of admission. Poor outcome was referred to as Glasgow Outcome Scale (GOS) scores of 1– 3 at 90 days post-stroke.
Results: As compared to controls, a significant increase in serum NOX4 levels was observed among patients. NOX4 levels were independently associated with GCS scores and hematoma volumes (all P< 0.05). The levels were significantly higher in patients with END than in those without, and in patients with poor outcome than in those with good outcome, as well as independently predicted both END (OR=3.166, 95% CI 1.237– 8.105, P=0.016) and 90-day poor prognosis (OR=3.031, 95% CI 1.111– 8.269, P=0.030). Serum NOX4 significantly differentiated patients at risk of END (area under ROC curve (AUC), 0.768; 95% confidence interval (CI), 0.695– 0.831) and poor prognosis (AUC, 0.777; 95% CI, 0.705– 0.839), which had similar prognostic ability, as compared to GCS scores and hematoma volumes (all P> 0.05).
Conclusion: Elevated serum NOX4 levels during the early period of sICH are closely related to stroke severity, END and poor neurological outcome. Hypothetically, serum NOX4 may serve as a potential prognostic biomarker in sICH.

Keywords: spontaneous intracerebral hemorrhage, NADPH oxidase 4, severity, early neurological deterioration, outcome, biomarkers