Cerebrospinal fluid biomarkers of white matter injury and astrogliosis are associated with the severity and surgical outcome of degenerative cervical spondylotic myelopathy

Abstract

Background context: Degenerative cervical spondylotic myelopathy (DCM) is the commonest form of spinal cord injury in adults. However, a limited number of clinical reports have assessed the role of biomarkers in DCM.

Purpose: We evaluated cerebrospinal fluid (CSF) biomarkers in patients scheduled for DCM surgery and hypothesized that CSF biomarkers levels (1) would reflect the severity of preoperative neurological status; and (2) correlate with radiological appearance; and (3) correlate with clinical outcome.

Study design/setting: Prospective clinical and laboratory study.

Patient sample: Twenty-three DCM patients, aged 66.4±12.8 years and seven controls aged 45.4±5.3 years were included.

Outcome measures: The American Spinal Injury Association Impairment Scale, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire and EuroQol 5-dimensions were assessed preoperatively and at 3 months post-surgery.

Methods: We measured preoperative biomarkers (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], phosphorylated neurofilament-H [pNF-H] and Ubiquitin C-terminal hydrolase L1) in CSF samples collected from patients with progressive clinical DCM who underwent surgical treatment. Biomarker concentrations in DCM patients were compared with those of cervical radiculopathy controls.

Results: The median symptom duration was 10 (interquartile range 6) months. The levels of GFAP, NFL, pNF-H, Ubiquitin C-terminal hydrolase L1 were significantly higher in the DCM group compared to controls (p=.044, p=.002, p=.016, and p=.006, respectively). Higher pNF-H levels were found in patients with low signal on T1 Magnetic Resonance Imaging sequence compared to those without (p=.022, area under the receiver operating characteristic curve [AUC] 0.780, 95% Confidence Interval: 0.59-0.98). Clinical improvement following surgery correlated mainly with NFL and GFAP levels (p<.05).

Conclusions: Our results suggest that CSF biomarkers of white matter injury and astrogliosis may be a useful tool to assess myelopathy severity and predict outcome after surgery, while providing valuable information on the underlying pathophysiology.

Keywords: Astrogliosis; Biomarkers; Degenerative cervical myelopathy; Prognosis; Spinal cord injury; White matter injury.