Acute Changes in Cerebrospinal Fluid 5-Hydroxyindoleacetic Acid Levels Correlate with Early Clinical Exam Changes and Long-Term Motor Function in Humans with Traumatic Spinal Cord Injury

Acute traumatic spinal cord injury comprises a primary mechanical injury followed by a delayed secondary cellular injury cascade. No current monitoring modality directly detects ongoing cellular damage or its response to treatment. Essentially all spinal serotonin derives from descending raphe-spinal projections that travel alongside spinal motor and sensory pathways. Experimental spinal cord injury results in a robust release of serotonin into the surrounding interstitial tissue. We therefore asked whether cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), the stable metabolite of serotonin, tracks primary and secondary spinal cord injury in humans. In this prospective observational cohort study at a single level-one trauma center, cerebrospinal fluid was collected at 8-hour intervals for up to 5 days through indwelling lumbar drains from 11 participants with acute cervical or thoracic traumatic spinal cord injuries (American Spinal Injury Association Impairment Scale [AIS] grade A-C) and from 7 non-injured control participants. Cerebrospinal fluid 5-HIAA was quantified by high-performance liquid chromatography. Participants with acute traumatic spinal cord injury demonstrated a reproducible rise in cerebrospinal fluid 5-HIAA within 12 hours of injury that regressed toward control values. Two participants neurologically declined during the 5-day observation period, and in both a delayed secondary 5-HIAA elevation accompanied the decline; in one participant this elevation coincided with a documented episode of critical spinal cord hypoperfusion and resolved within 8 hours of its correction. Across the cohort, the 5 participants with a secondary 5-HIAA elevations above 400 nM more than 36 hours after index trauma were AIS A at 12 months regardless of initial injury severity, whereas all 6 participants without a secondary elevation in cerebrospinal fluid 5-HIAA levels were AIS C or better. In this small exploratory cohort, cerebrospinal fluid 5-HIAA was associated with the presence of acute traumatic spinal cord injury, with acute secondary neurological decline, and with long-term motor outcome. Unlike glial fibrillary acidic protein and neurofilament light chain, whose concentrations evolve over days to weeks, 5-HIAA rose and regresses within hours, a kinetic profile compatible with real-time detection of secondary injury and confirmation of treatment response. These findings are hypothesis-generating and require validation in larger, multicenter cohorts before clinical application.