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 longterm 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= 0.02), and GOS at 3-(p= 0.01), 6-(p= 0.04), 12-(p= 0.007), and 24-months (p=0.002). 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,

Raman Spectroscopy as a Neuromonitoring Tool in Traumatic Brain Injury: A Systematic Review and Clinical Perspectives

“…Rickard et al [ 64 ] developed an optofluidic device using SERS capable of detecting picomolar concentrations of N -acetylaspartate (NAA) [ 64 ]. NAA is an abundant molecule in the central nervous system (CNS) which is released following TBI and is believed to correlate with injury severity and poor prognosis [ 65 ]. The device was also able to detect and discriminate concentrations of S100B and GFAP, (glial fibrillary acidic protein) also recognised biomarkers of neurological injury burden [ 66 ].…”

“…A number of studies have utilised RS (or a variation thereof) in developing point-of-care applicable diagnostic devices for the recognition of biomarkers of TBI [ 64 , 65 , 66 , 67 , 68 , 69 ]. Point-of-care detection for TBI has the most relevance in mild TBI and particularly concussion.…”