Elevated cerebrospinal fluid concentrations of N-acetylaspartate correlate with poor outcome in a pilot study of severe brain trauma

ABSTRACT

Primary objective: Examine the correlation between acute cerebrospinal fluid (CSF) levels of N-acetylaspartate (NAA) and injury severity upon admission in addition to long-term functional outcomes of severe traumatic brain injury (TBI).

Design and rationale: This exploratory study assessed CSF NAA levels in the first four days after severe TBI, and correlated these findings with Glasgow Coma Scale (GCS) score and long-term outcomes at 3, 6, 12, and 24 months post-injury.

Methods: CSF was collected after passive drainage via an indwelling ventriculostomy placed as standard of care in a total of 28 people with severe TBI. NAA levels were assayed using triple quadrupole mass spectrometry. Functional outcomes were assessed using the Glasgow Outcomes Scale (GOS) and Disability Rating Scale (DRS).

Results: In this pilot study, better functional outcomes, assessed using the GOS and DRS, were found in individuals with lower acute CSF NAA levels after TBI. Key findings were that average NAA level was associated with GCS (p = .02), and GOS at 3 (p = .01), 6 (p = .04), 12 (p = .007), and 24 months (p = .002).

Implications: The results of this study add to a growing body of neuroimaging evidence that raw NAA values are reduced and variable after TBI, potentially impacting patient outcomes, warranting additional exploration into this finding. This line of inquiry could lead to improved diagnosis and prognosis in patients with TBI.

KEYWORDS:

• Traumatic brain injury (TBI)
• brain trauma
• severe TBI
• N-acetylaspartate (NAA)
• biomarker

Acknowledgments

The authors would like to thank the persons with severe TBI and families who participated in this study, Sandra Deslouches for her laboratory technical assistance, as well as Michael D. Farmer and Marilyn K. Farmer for their editorial support.

Conflict of interest

The authors declare that they have no conflicts of interest to report.

Additional information

Funding

Funds in support of this study were provided by the National Institute of Nursing Research [R00NR013176 and R01NR01334] and the National Institute of Neurological Disorders and Stroke [P50NS30318].