Ratio of Nitric Oxide Metabolite Levels in Cerebrospinal Fluid and Serum, and Their Correlation with Severity and Outcome in Patients with Subarachnoid Haemorrhage

BACKGROUND: Nitric oxide (NO) is involved in a multitude of physiological processes in the central nervous system (CNS). Given the ubiquitous nature of NO and its involvement in various vital processes, nitric oxide metabolite (NOx) has been investigated as a biomarker in CNS diseases. This study aims to investigate the ratio of NOx levels and serum in cerebrospinal fluid (CSF) in patients with spontaneous subarachnoid haemorrhage (SAH). The associations among these markers with clinical outcomes were also studied.

METHODS: A prospective cohort study was conducted over a 2-year period (May 2013-May 2015) to investigate the levels of NOx in the CSF and serum of patients with radiologically confirmed aneurysmal SAH. NOx samples and all relevant data were collected from the patients on admission and serially over 5 days. On admission, NOx levels were compared between the groups of patients, who were divided as per the World Federation Neurosurgeons Score (WFNS) grading scale, Fisher scale, occurrence of vasospasm on transcranial doppler (TCD), and Glasgow outcome scale (GOS) upon discharge and at 6 months follow-up. The ratios of CSF-to-serum were calculated and correlated with SAH severity and the outcome parameters listed above.

RESULTS: The patients (N = 40) had a mean (SD) age of 58.2 (11.8) years old. The majority (65%) had a higher severity of SAH (WFNS score 3-5). On evaluation of the CT scan findings, 74% had outcomes equivalent to 4 on the Fisher scale. Vasospasm was detected via TCD in nearly half (45%) of the cohort during the study period; 80% were noted to have a poor outcome (GOS 1-3) at discharge; this persisted at 6 months follow-up. Comparison of NOx levels in the CSF/serum ratio was based on the incidence of vasospasm and severity of outcome (GOS) for day-1 and day-4. Statistically significant results were evident for patients with better outcomes, high severity grading, and the presence of vasospasm (P-values: 0.031, 0.034 and 0.043, respectively).

CONCLUSION: Elevated NOx levels in CSF and serum and reductions in the ratio of NOx in CSF/serum were found to be associated with severity, occurrence of vasospasm and clinical outcome in aneurysmal SAH patients. This indicates the possible role of NOx as a biomarker to assess severity and prognosis in patients with SAH.