Richard Bostelmann1, Tamara Bostelmann2, Adrian Nasaca2, Hans Jakob Steiger2, Frank Zaucke3, Christoph Schleich4. 1. Department of Neurosurgery, University Hospital of Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany. Electronic address: richard.bostelmann@med.uni-duesseldorf.de. 2. Department of Neurosurgery, University Hospital of Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany. 3. Institute for Biochemistry II, Medical Faculty, University of Cologne, Joseph Stelzmann Str. 52, D-50931 Cologne, Germany; Dr. Rolf Schwiete Research Unit for Osteoarthritis Orthopedic University Hospital, Friedrichsheim gGmbH Marienburgstr. 2, 60528, Frankfurt/Main. 4. Department of Diagnostic and Interventional Radiology, University Hospital Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany.
Abstract
BACKGROUND CONTEXT: On a molecular level, maturation or degeneration of human intervertebral disc is among others expressed by the content of glycosaminoglycans (GAGs). According to the degenerative status, the disc content can differ in nucleus pulposus (NP) and annulus fibrosus (AF), respectively. Research in this area was conducted mostly on postmortem samples. Although several radiological classification systems exist, none includes biochemical features. Therefore, we focused our in vivo study on a widely spread and less expensive imaging technique for the cervical spine and the correlation of radiological patterns to biochemical equivalents in the intervertebral discs. PURPOSE: The aim of this pilot study was to (1) measure the GAG content in human cervical discs, (2) to investigate whether a topographic biochemical GAG pattern can be found, and (3) whether there is a correlation between imaging data (X-ray and magnetic resonance imaging [MRI] including delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] as a special imaging technique of cartilage) and the biochemical data. STUDY DESIGN/SAMPLE: We conducted a prospective experimental pilot study. PATIENT SAMPLE: Only non-responders to conservative therapy were included. All subjects were physically and neurologically examined, and they completed their questionnaires. OUTCOME MEASURES: Visual analogue scale neck and arm, Neck Disability Index score, radiological parameters (X-rays, MRI, dGEMRIC), and the content of GAG in the cervical disc were assessed. METHODS: After surgical removal of 12 discs, 96 fractions of AF and NP were biochemically analyzed for the GAG content using dimethylmethylene blue assay. RESULTS: A quantitative pattern of GAGs in the human cervical disc was identified. There were (1) significantly (p<.001) higher values of GAGs (µg GAG/mg tissue) in the NP (169.9 SD 37.3) compared with the AF (132.4 SD 42.2), and (2) significantly (p<.005) higher values of GAGs in the posterior (right/left: 149.9/160.2) compared with the anterior (right/left: 112.0/120.2) part of the AF. Third, we found in dGEMRIC imaging a significantly (p<.008) different distribution of GAGs in the cervical disc (NP 1083.3 ms [SD 248.6], AF 925.9 ms [SD 137.6]). Finally, we found that grading of disc degeneration in X-ray and MRI was significantly correlated with neither AF- nor NP-GAG content. CONCLUSIONS: The GAG content in human cervical discs can be detected in vivo and is subject to a significantly (p<.05) region-specific pattern (AF vs. NP; anterior vs. posterior in the AF). Up to the levels of AF and NP, this is reproducible in MRI in dGEMRIC technique, but not in X-ray or standard MRI sequences. Potentially, the MRI in dGEMRIC technique can be used as a non-invasive in vivo indicator for disc degeneration in the cervical spine.
BACKGROUND CONTEXT: On a molecular level, maturation or degeneration of human intervertebral disc is among others expressed by the content of glycosaminoglycans (GAGs). According to the degenerative status, the disc content can differ in nucleus pulposus (NP) and annulus fibrosus (AF), respectively. Research in this area was conducted mostly on postmortem samples. Although several radiological classification systems exist, none includes biochemical features. Therefore, we focused our in vivo study on a widely spread and less expensive imaging technique for the cervical spine and the correlation of radiological patterns to biochemical equivalents in the intervertebral discs. PURPOSE: The aim of this pilot study was to (1) measure the GAG content in human cervical discs, (2) to investigate whether a topographic biochemical GAG pattern can be found, and (3) whether there is a correlation between imaging data (X-ray and magnetic resonance imaging [MRI] including delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] as a special imaging technique of cartilage) and the biochemical data. STUDY DESIGN/SAMPLE: We conducted a prospective experimental pilot study. PATIENT SAMPLE: Only non-responders to conservative therapy were included. All subjects were physically and neurologically examined, and they completed their questionnaires. OUTCOME MEASURES: Visual analogue scale neck and arm, Neck Disability Index score, radiological parameters (X-rays, MRI, dGEMRIC), and the content of GAG in the cervical disc were assessed. METHODS: After surgical removal of 12 discs, 96 fractions of AF and NP were biochemically analyzed for the GAG content using dimethylmethylene blue assay. RESULTS: A quantitative pattern of GAGs in the human cervical disc was identified. There were (1) significantly (p<.001) higher values of GAGs (µg GAG/mg tissue) in the NP (169.9 SD 37.3) compared with the AF (132.4 SD 42.2), and (2) significantly (p<.005) higher values of GAGs in the posterior (right/left: 149.9/160.2) compared with the anterior (right/left: 112.0/120.2) part of the AF. Third, we found in dGEMRIC imaging a significantly (p<.008) different distribution of GAGs in the cervical disc (NP 1083.3 ms [SD 248.6], AF 925.9 ms [SD 137.6]). Finally, we found that grading of disc degeneration in X-ray and MRI was significantly correlated with neither AF- nor NP-GAG content. CONCLUSIONS: The GAG content in human cervical discs can be detected in vivo and is subject to a significantly (p<.05) region-specific pattern (AF vs. NP; anterior vs. posterior in the AF). Up to the levels of AF and NP, this is reproducible in MRI in dGEMRIC technique, but not in X-ray or standard MRI sequences. Potentially, the MRI in dGEMRIC technique can be used as a non-invasive in vivo indicator for disc degeneration in the cervical spine.
Authors: Cindy C Shu; Margaret M Smith; Susan M Smith; Andrew J Dart; Christopher B Little; James Melrose Journal: Int J Mol Sci Date: 2017-05-12 Impact factor: 5.923