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Association of CSF and Serum Neurofilament Light and Glial Fibrillary Acidic Protein, Injury Severity, and Outcome in Spinal Cord Injury

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, 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

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

Background and Objectives

Traumatic spinal cord injury (SCI) is highly heterogeneous, and tools to better delineate pathophysiology and recovery are needed. Our objective was to profile the response of 2 biomarkers, neurofilament light (NF-L) and glial fibrillary acidic protein (GFAP), in the serum and CSF of patients with acute SCI to evaluate their ability to objectively characterize injury severity and predict neurologic recovery.

Methods

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

Methods

Data were collected anonymously from an online survey between February and May 2020.

Results
One hundred eighteen patients with acute SCI (78 AIS A, 20 AIS B, and 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, were both 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% CI) of 76% (61, 87) and 77% (55, 92) using NF-L and 72% (57, 84) and 77% (55, 92) using GFAP at 72 hours, respectively. Independent of clinical baseline assessment, a serum NF-L threshold of 170 pg/mL at 72 hours predicted those patients who would be classified as motor complete (AIS A/B) compared with 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 72 hours yielded a sensitivity of 90% (80, 96) and specificity of 84% (69, 94).

Funding
The authors gratefully acknowledge clinical trial funding from the Praxis Spinal Cord Institute and grant support to conduct this biomarker analysis from the Paralyzed Veterans of America and the Blusson Integrated Cures Program seed grants program.

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