Journal of Neurology, Neurosurgery & Neuropsychiatry | June 2, 2024

Olde Heuvel, F., Li, Z., Riedel, D., Halbgebauer, S., Oeckl, P., Mayer, B., Gotzman, N., Shultz, S., Semple, B., Tumani, H., Ludolph, A. C., Boeckers, T. M., Morganti-Kossmann, C., Otto, M., & Roselli, F.

Journal of neurology, neurosurgery, and psychiatry

https://doi.org/10.1136/jnnp-2024-333413

This study was performed using the Quanterix HD-1 Analyzer.

This study was performed using Simoa Homebrew assay(s).

Abstract

Background Biomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI, but biomarkers of synaptic damage in human patients have not been explored.

Methods Single-molecule array assays were used to measure synaptosomal-associated protein-25 (SNAP-25) and visinin-like protein 1 (VILIP-1) (along with neurofilament light chain (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillar acidic protein (GFAP), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in ventricular cerebrospinal fluid (CSF) samples longitudinally acquired during the intensive care unit (ICU) stay of 42 patients with severe TBI or 22 uninjured controls.

Results CSF levels of SNAP-25 and VILIP-1 are strongly elevated early after severe TBI and decline in the first few days. SNAP-25 and VILIP-1 correlate with inflammatory markers at two distinct timepoints (around D1 and then again at D5) in follow-up. SNAP-25 and VILIP-1 on the day-of-injury have better sensitivity and specificity for unfavourable outcome at 6 months than NFL, UCH-L1 or GFAP. Later elevation of SNAP-25 was associated with poorer outcome.

Conclusion Synaptic damage markers are acutely elevated in severe TBI and predict long-term outcomes, as well as, or better than, markers of neuroaxonal injury. Synaptic damage correlates with initial injury and with a later phase of secondary inflammatory injury.