Parmenion P Tsitsopoulos1,2, Ulrika Holmström1, Kaj Blennow3,4, Henrik Zetterberg3,4,5,6, Niklas Marklund1,7. 1. 1Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden. 2. 2Department of Neurosurgery, Hippokratio General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece. 3. 3Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal. 4. 4Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 5. 5Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London. 6. 6UK Dementia Research Institute at University College of London, United Kingdom; and. 7. 7Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Neurosurgery, Lund, Sweden.
Abstract
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.
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.