Neurology | January 4, 2023

Sophie Stukas, Jennifer Cooper, Jasmine Gill, Nader Fallah, Michael A Skinnider, Lise Belanger, Leanna Ritchie, Angela Tsang, Kevin Dong, Femke Streijger, John Street, Scott Paquette FRSCS, Tamir Ailon, Nicolas Dea, Raphaele Charest-Morin, Charles G Fisher, Christopher S Bailey, Sanjay Dhall, Jean-Marc Mac-Thiong, Jefferson R Wilson, Sean Christie, Marcel F Dvorak, Cheryl L Wellington, Brian K Kwon

Neurology Jan 2023, 10.1212/WNL.0000000000206744

https://doi.org/10.1212/WNL.0000000000206744

Abstract

Background and Objective: Traumatic spinal cord injury (SCI) is highly heterogenous and tools to better delineate pathophysiology and recovery are needed. Our objective was to profile the response of two biomarkers, neurofilament light (NF-L) and glial fibrillary acidic protein (GFAP), in the serum and CSF of acute SCI patients to evaluate their ability to objectively characterize injury severity and predict neurologic recovery.

Methods: Blood and CSF samples were obtained from prospectively enrolled acute SCI patients through days 1-4 post-injury, and the concentration of NF-L and GFAP was quantified using Simoa^TM technology. Neurologic assessments defined the ASIA Impairment Scale (AIS) grade and motor score (MS) at presentation and 6-months post-injury.

Results: 118 acute SCI patients (78 AIS A, 20 AIS B, 20 AIS C) were enrolled with 113 (96%) completing 6-month follow-up. NF-L and GFAP levels were strongly associated between paired serum and CSF specimens, increased with injury severity, and distinguished among baseline AIS grades. Serum NF-L and GFAP were significantly (P=0.02 to <0.0001) higher in AIS A patients who did not improve at 6-months, predicting AIS grade conversion with a sensitivity and specificity (95% confidence interval) of 76% (61, 87) and 77% (55, 92) using NF-L, and 72% (57, 84) and 77% (55, 92) using GFAP at 72h, respectively. Independent of clinical baseline assessment, a serum NF-L threshold of 170 pg/ml at 72h predicted those patients who would be classified as “motor complete” (AIS A/B) compared to “motor incomplete” (AIS C/D) at 6 months with a sensitivity of 87% (76, 94) and specificity of 84% (69, 94); a serum GFAP threshold of 13,180 pg/ml at 72h yielded a sensitivity of 90% (80, 96) and specificity of 84% (69, 94).

Discussion: The potential for NF-L and GFAP to classify injury severity and predict outcome after acute SCI will be useful for patient stratification and prognostication in clinical trials, and inform communication of prognosis.