To Örebro University

Objective: The study aims to examine alpha-synuclein in the CSF of patients with severe traumatic brain injury (TBI) and its relationship with clinical characteristics and long-term outcomes.

Methods: This prospective case-control study enrolled patients with severe TBI (Glasgow Coma Score <= 8) who underwent ventriculostomy. CSF samples were taken from each TBI patient at admission and daily for up to 8 days after injury and successively assessed by ELISA. Control CSF was collected for analysis from subjects receiving lumbar puncture for other medical reasons. We used trajectory analysis to identify distinct temporal profiles of CSF alpha-synuclein that were compared with clinical outcomes.

Results: CSF alpha-synuclein was elevated in TBI patients after injury as compared to controls (p = 0.0008). Overall, patients who died had higher concentrations (area under the curve) over 8 days of observation compared to those who survived at 6 months postinjury (p = 0.002). Two distinct temporal alpha-synuclein profiles were recognized over time. Subjects who died had consistently elevated alpha-synuclein levels compared to those who survived with alpha-synuclein levels near controls. High-risk trajectory was a strong and accurate predictor of death with 100% specificity and a very high sensitivity (83%).

Conclusions: Taken together, these data support the hypothesis that in severe TBI patients, substantial increase of CSF alpha-synuclein may indicate widespread neurodegeneration and reflect secondary neuropathologic events occurring after injury. The determination of CSF alpha-synuclein may be a valuable prognostic marker, adding to the clinical assessment and creating opportunities for medical intervention.