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

Tsitsopoulos, Parmenion P. ; Holmström, Ulrika ; Blennow, Kaj LU ; Zetterberg, Henrik LU and Marklund, Niklas LU orcid (2021) In Journal of Neurosurgery: Spine 34(4). p.632-641
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... (More)

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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Axonal damage, Biomarkers, Cervical spondylotic myelopathy, Glial injury, Prognosis
in
Journal of Neurosurgery: Spine
volume
34
issue
4
pages
10 pages
publisher
American Association of Neurological Surgeons
external identifiers
  • scopus:85103439612
  • pmid:33513577
ISSN
1547-5654
DOI
10.3171/2020.8.SPINE20965
language
English
LU publication?
yes
id
3801a22f-f433-44fe-8129-f65ccb3381ea
date added to LUP
2021-04-12 09:53:32
date last changed
2024-06-15 09:39:54
@article{3801a22f-f433-44fe-8129-f65ccb3381ea,
  abstract     = {{<p>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 &lt; 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 &gt; 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 &lt; 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 &lt; 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 &lt; 0.05). CSF NF-L and FABP3 levels were higher in patients with improved outcome (EQ-5D visual analog scale difference &gt; 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.</p>}},
  author       = {{Tsitsopoulos, Parmenion P. and Holmström, Ulrika and Blennow, Kaj and Zetterberg, Henrik and Marklund, Niklas}},
  issn         = {{1547-5654}},
  keywords     = {{Axonal damage; Biomarkers; Cervical spondylotic myelopathy; Glial injury; Prognosis}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{632--641}},
  publisher    = {{American Association of Neurological Surgeons}},
  series       = {{Journal of Neurosurgery: Spine}},
  title        = {{Cerebrospinal fluid biomarkers of glial and axonal injury in cervical spondylotic myelopathy}},
  url          = {{http://dx.doi.org/10.3171/2020.8.SPINE20965}},
  doi          = {{10.3171/2020.8.SPINE20965}},
  volume       = {{34}},
  year         = {{2021}},
}