Usefulness of Serum NOX4 as a Potential Biomarker to Predict Early Neurological Deterioration and Poor Outcome of Spontaneous Intracerebral Hemorrhage: A Prospective Observational Study

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.