Cerebrospinal fluid biomarkers of glial and axonal injury in cervical spondylotic myelopathy

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  • 1 Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden;
  • 2 Department of Neurosurgery, Hippokratio General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece;
  • 3 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal;
  • 4 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden;
  • 5 Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London;
  • 6 UK Dementia Research Institute at University College of London, United Kingdom; and
  • 7 Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Neurosurgery, Lund, Sweden
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OBJECTIVE

Degenerative cervical spondylotic myelopathy (CSM) is a major cause of spinal cord dysfunction with an unpredictable prognosis. Βiomarkers reflecting pathophysiological processes in CSM have been insufficiently investigated. It was hypothesized that preoperative cerebrospinal fluid (CSF) biomarker levels are altered in patients with CSM and correlate with neurological status and outcome.

METHODS

CSF biomarkers from patients with CSM and controls were analyzed with immunoassays. Spinal cord changes were evaluated with MRI. The American Spinal Cord Injury Association Impairment Scale, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and the EQ-5D questionnaire were applied prior to and 3 months after surgery. A p value < 0.05 was considered statistically significant.

RESULTS

Twenty consecutive CSM patients with a mean age of 67.7 ± 13 years and 63 controls with a mean age of 65.2 ± 14.5 years (p > 0.05) were included in the study. In the CSM subjects, CSF neurofilament light subunit (NF-L) and glial fibrillary acidic protein (GFAP) concentrations were higher (p < 0.05), whereas fatty acid–binding protein 3 (FABP3), soluble amyloid precursor proteins (sAPPα and sAPPβ), and amyloid β (Aβ) peptide (Aβ38, Aβ40, and Aβ42) concentrations were lower than in controls (p < 0.05). Aβ peptide levels correlated positively with symptom duration. Preoperative JOACMEQ lower extremity function and CSF NF-L levels correlated positively, and the JOACMEQ bladder function correlated negatively with sAPPα and sAPPβ (p < 0.05). CSF NF-L and FABP3 levels were higher in patients with improved outcome (EQ-5D visual analog scale difference > 20).

CONCLUSIONS

CSF biomarkers of glial and axonal damage, inflammation, and synaptic changes are altered in symptomatic CSM patients, indicating that axonal injury, astroglial activation, and Aβ dysmetabolism may be present in these individuals. These findings reflect CSM pathophysiology and may aid in prognostication. However, future studies including larger patient cohorts, postoperative biomarker data and imaging, and longer follow-up times are required to validate the present findings.

ABBREVIATIONS Aβ = amyloid β; ACDF = anterior cervical discectomy and fusion; AIS = American Spinal Injury Association Impairment Scale; AUROC = area under the receiver operating characteristic curve; CNS = central nervous system; CSF = cerebrospinal fluid; CSM = cervical spondylotic myelopathy; EQ-VAS = EQ-5D visual analog scale; FABP3 = heart-type fatty acid–binding protein; GFAP = glial fibrillary acidic protein; JOACMEQ = Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire; NF-L = neurofilament light subunit; pNF-H = phosphorylated neurofilament heavy subunit; sAPP = soluble amyloid precursor protein; SCI = spinal cord injury; YKL-40 = chitinase-3-like protein 1.

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Contributor Notes

Correspondence Parmenion P. Tsitsopoulos: Hippokratio General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece. ptsitsopoulos@auth.gr.

INCLUDE WHEN CITING Published online January 29, 2021; DOI: 10.3171/2020.8.SPINE20965.

P.P.T. and U.H. contributed equally to this work.

Disclosures Dr. Blennow is a consultant for Abcam, Axon, Biogen, JOMDD/Shimadzu, Eli Lilly, MagQu, Roche Diagnostics, Fujirebio Europe, IBL International, Novartis, and Siemens Healthineers; receives support from Julius Clinical and Novartis for work unrelated to this study; and has ownership of Brain Biomarker Solutions. Dr. Zetterberg has ownership of Brain Biomarker Solutions; is a consultant for Denali, Wave, Roche Diagnostics, Samumed, and CogRx; and has received honoraria from Fujirebio, Biogen, and Alzecure. Dr. Marklund is a consultant for PolarCool Inc.

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