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Zheng Z, Chen J, Xu J, Jiang B, Li L, Li Y, Dai Y, Wang B. Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy. Neural Regen Res 2025; 20:1764-1775. [PMID: 39104114 PMCID: PMC11688566 DOI: 10.4103/nrr.nrr-d-23-01069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 10/10/2023] [Accepted: 11/23/2023] [Indexed: 08/07/2024] Open
Abstract
JOURNAL/nrgr/04.03/01300535-202506000-00027/figure1/v/2024-08-05T133530Z/r/image-tiff Degenerative cervical myelopathy is a common cause of spinal cord injury, with longer symptom duration and higher myelopathy severity indicating a worse prognosis. While numerous studies have investigated serological biomarkers for acute spinal cord injury, few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy. This study involved 30 patients with degenerative cervical myelopathy (51.3 ± 7.3 years old, 12 women and 18 men), seven healthy controls (25.7 ± 1.7 years old, one woman and six men), and nine patients with cervical spondylotic radiculopathy (51.9 ± 8.6 years old, three women and six men). Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics. Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities. Using least absolute shrinkage and selection operator analysis, we constructed a five-gene model (TBCD, TPM2, PNKD, EIF4G2, and AP5Z1) to diagnose degenerative cervical myelopathy with an accuracy of 93.5%. One-gene models (TCAP and SDHA) identified mild and severe degenerative cervical myelopathy with accuracies of 83.3% and 76.7%, respectively. Signatures of two immune cell types (memory B cells and memory-activated CD4+ T cells) predicted levels of lesions in degenerative cervical myelopathy with 80% accuracy. Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
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Affiliation(s)
- Zhenzhong Zheng
- Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
| | - Jialin Chen
- Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
| | - Jinghong Xu
- Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
| | - Bin Jiang
- Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
| | - Lei Li
- Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
| | - Yawei Li
- Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
| | - Yuliang Dai
- Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
| | - Bing Wang
- Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
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Bédard S, Valošek J, Seif M, Curt A, Schading-Sassenhausen S, Pfender N, Freund P, Hupp M, Cohen-Adad J. Normalizing spinal cord compression measures in degenerative cervical myelopathy. Spine J 2025:S1529-9430(25)00159-7. [PMID: 40154634 DOI: 10.1016/j.spinee.2025.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 01/06/2025] [Accepted: 03/22/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND CONTEXT Accurate and automatic MRI measurements are relevant for assessing spinal cord compression severity in degenerative cervical myelopathy (DCM) and guiding treatment. The widely-used maximum spinal cord compression (MSCC) index has limitations. Firstly, it normalizes the anteroposterior cord diameter by that above and below the compression but does not account for cord size variation along the superior-inferior axis, making MSCC sensitive to compression level. Secondly, cord shape varies across individuals, making MSCC sensitive to this variability. Thirdly, MSCC is typically calculated by an expert-rater from a single sagittal slice, which is time-consuming and prone to variability. PURPOSE This study proposes a fully automatic pipeline to compute MSCC. DESIGN We developed a normalization strategy for traditional MSCC (anteroposterior diameter) using a healthy adults database (n = 203) to address cord anatomy variability across individuals and evaluated additional morphometrics (transverse diameter, area, eccentricity, and solidity). PATIENT SAMPLE DCM patient cohort of n = 120. OUTCOME MEASURES Receiver operating characteristic (ROC) and area under the curve (AUC) were used as evaluation metrics. METHODS We validated the method in a mild DCM patient cohort against manually derived morphometrics and predicted the therapeutic decision (operative/conservative) using a stepwise binary logistic regression incorporating demographics and clinical scores. RESULTS The automatic and normalized MSCC measures correlated significantly with clinical scores and predicted the therapeutic decision more accurately than manual MSCC. Significant predictors included upper extremity sensory dysfunction, T2w hyperintensity, and the proposed MRI-based measures. The model achieved an area under the curve of 0.80 in receiver operating characteristic analysis. CONCLUSION This study introduced an automatic method for computing normalized measures of cord compressions from MRIs, potentially improving therapeutic decisions in DCM patients. The method is open-source and available in Spinal Cord Toolbox v6.0 and above.
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Affiliation(s)
- Sandrine Bédard
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, 2500 Chem. de Polytechnique, Montréal, H3T 1J4, Québec, Canada
| | - Jan Valošek
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, 2500 Chem. de Polytechnique, Montréal, H3T 1J4, Québec, Canada; Mila - Quebec AI Institute, 6666 Rue Saint-Urbain, Montréal, H2S 3H1, Québec, Canada; Department of Neurosurgery, Faculty of Medicine and Dentistry, Palacký University Olomouc, 775 15, Hněvotínská 976/3, Nová Ulice, 779 00 Olomouc, Czechia; Department of Neurology, Faculty of Medicine and Dentistry, Palacký University Olomouc, 775 15, Hněvotínská 976/3, Nová Ulice, 779 00 Olomouc, Czechia
| | - Maryam Seif
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008 Zurich, Switzerland; Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany
| | - Armin Curt
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008 Zurich, Switzerland
| | - Simon Schading-Sassenhausen
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008 Zurich, Switzerland
| | - Nikolai Pfender
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008 Zurich, Switzerland
| | - Patrick Freund
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008 Zurich, Switzerland; Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany; Wellcome Trust Centre for Neuroimaging, Queen Square Institute of Neurology, University College London, 12 Queen Square, London WC1N 3AR, United Kingdom
| | - Markus Hupp
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008 Zurich, Switzerland
| | - Julien Cohen-Adad
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, 2500 Chem. de Polytechnique, Montréal, H3T 1J4, Québec, Canada; Mila - Quebec AI Institute, 6666 Rue Saint-Urbain, Montréal, H2S 3H1, Québec, Canada; Functional Neuroimaging Unit, CRIUGM, University of Montreal, 4545, Queen Mary Road, Montreal, H3W 1W4, Quebec, Canada; Centre de recherche du CHU Sainte-Justine, Université de Montréal, 4545 Chem. Queen Mary, Montréal, H3W 1W4, Quebec, Canada.
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Pfender N, Jutzeler CR, Hubli M, Scheuren PS, Pfyffer D, Zipser CM, Rosner J, Friedl S, Sutter R, Spirig JM, Betz M, Schubert M, Seif M, Freund P, Farshad M, Curt A, Hupp M. Potential thresholds of critically increased cardiac-related spinal cord motion in degenerative cervical myelopathy. Front Neurol 2024; 15:1411182. [PMID: 38978814 PMCID: PMC11228334 DOI: 10.3389/fneur.2024.1411182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 06/11/2024] [Indexed: 07/10/2024] Open
Abstract
Introduction New diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord. Methods Eighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI- (no T2w-hyperintense lesion). Cord motion (displacement assessed by phase-contrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis. Results MRI+ patients (N = 31; 36.9%) were more impaired compared to MRI- patients (N = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4-5); MRI-: 5 (5-5); p < 0.01} and lower extremity [MRI+: 6 (6-7); MRI-: 7 (6-7); p = 0.03] motor dysfunction and the monofilament score [MRI+: 21 (18-23); MRI-: 24 (22-24); p < 0.01]. Both patient groups showed similar extent of cord motion and stenosis. Only in the MRI- group displacement identified patients with pathologic assessments [trunk/lower extremity pin prick score (T/LEPP): AUC = 0.67, p = 0.03; CHEPs: AUC = 0.73, p = 0.01]. Cord motion thresholds: T/LEPP: 1.67 mm (sensitivity 84.6%, specificity 52.5%); CHEPs: 1.96 mm (sensitivity 83.3%, specificity 65.6%). The aSCOR failed to show any relation to the clinical assessments. Discussion These findings affirm cord motion measurements as a promising additional biomarker to improve the clinical workup and to enable timely surgical treatment particularly in MRI- DCM patients. Clinical trial registration www.clinicaltrials.gov, NCT02170155.
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Affiliation(s)
- Nikolai Pfender
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | | | - Michèle Hubli
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Paulina S Scheuren
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
- International Collaboration on Repair Discoveries (ICORD), Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Dario Pfyffer
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
- School of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA, United States
| | - Carl M Zipser
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Jan Rosner
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
- Department of Neurology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Susanne Friedl
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Reto Sutter
- Department of Radiology, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - José M Spirig
- University Spine Center Zurich, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Michael Betz
- University Spine Center Zurich, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Martin Schubert
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Maryam Seif
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Patrick Freund
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Mazda Farshad
- University Spine Center Zurich, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Armin Curt
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
- University Spine Center Zurich, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Markus Hupp
- Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
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Wang C, Han X, Ma X, Jiang W, Wang J, Li S, Guo H, Tian W, Chen H. Spinal cord perfusion is associated with microstructural damage in cervical spondylotic myelopathy patients who underwent cervical laminoplasty. Eur Radiol 2024; 34:1349-1357. [PMID: 37581664 DOI: 10.1007/s00330-023-10011-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 05/01/2023] [Accepted: 06/08/2023] [Indexed: 08/16/2023]
Abstract
OBJECTIVES To investigate the association between spinal cord perfusion and microstructural damage in CSM patients who underwent cervical laminoplasty using MR dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) techniques. METHODS A follow-up cohort study was conducted with 53 consecutively recruited CSM patients who had undergone cervical laminoplasty 12-14 months after the surgery from April 2016 to December 2016. Twenty-one aged-matched healthy volunteers were recruited as controls. For each patient, decompressed spinal cord levels were imaged on a 3.0-T MRI scanner by diffusion and DSC sequences to quantify the degrees of microstructural damage and perfusion conditions, respectively. The diffusion data were analyzed by DTI and NODDI models to produce diffusion metrics. Classic indicator dilution model was used to quantify the DSC metrics. Mann-Whitney U test was performed for comparison of diffusion metrics between patients and healthy controls. Pearson correlation was used to explore the associations between the metrics of spinal cord perfusion and microstructural damage. RESULTS DTI metrics, neurite density, and isotropic volume fraction had significant differences between postoperative patients and healthy controls. Pearson correlation test showed that SCBV was significantly positively correlated with RD, MD, and ODI, and negatively correlated with FA and NDI. SCBF was found to be significantly positively correlated with RD and MD, and negatively correlated with FA. CONCLUSIONS Increased spinal cord perfusion quantified by DSC is associated with microstructural damage assessed by diffusion MRI in CSM patients who underwent cervical laminoplasty. CLINICAL RELEVANCE STATEMENT This study found that the spinal cord perfusion is associated with microstructural damage in postoperative cervical spondylotic myelopathy patients, indicating that high perfusion may play a role in the pathophysiological process of cervical spondylotic myelopathy and deserves more attention. KEY POINTS • Spinal cord microstructural damage can be persistent despite the compression had been relieved 12-14 months after the cervical laminoplasty in cervical spondylotic myelopathy (CSM) patients. • Spinal cord perfusion is associated with microstructural damage in CSM patients after the cervical laminoplasty. • Inflammation in the decompressed spinal cord may be a cause of increased perfusion and is associated with microstructural damage during the recovery period of CSM.
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Affiliation(s)
- Chunyao Wang
- Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
| | - Xiao Han
- Department of Spine Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
- Beijing Research Institute of Traumatology and Orthopaedics, Beijing, China
| | - Xiaodong Ma
- Center for Magnetic Resonance Research, Radiology, Medical School of the University of Minnesota, Minnesota, USA
| | - Wen Jiang
- Department of Radiology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Jinchao Wang
- Department of Spine Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Sisi Li
- Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
| | - Hua Guo
- Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
| | - Wei Tian
- Department of Spine Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
| | - Huijun Chen
- Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.
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Song J, Li J, Zhao R, Chu X. Developing predictive models for surgical outcomes in patients with degenerative cervical myelopathy: a comparison of statistical and machine learning approaches. Spine J 2024; 24:57-67. [PMID: 37531977 DOI: 10.1016/j.spinee.2023.07.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/16/2023] [Accepted: 07/26/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND CONTEXT Machine learning (ML) is widely used to predict the prognosis of numerous diseases. PURPOSE This retrospective analysis aimed to develop a prognostic prediction model using ML algorithms and identify predictors associated with poor surgical outcomes in patients with degenerative cervical myelopathy (DCM). STUDY DESIGN A retrospective study. PATIENT SAMPLE A total of 406 symptomatic DCM patients who underwent surgical decompression were enrolled and analyzed from three independent medical centers. OUTCOME MEASURES We calculated the area under the curve (AUC), classification accuracy, sensitivity, and specificity of each model. METHODS The Japanese Orthopedic Association (JOA) score was obtained before and 1 year following decompression surgery, and patients were grouped into good and poor outcome groups based on a cut-off value of 60% based on a previous study. Two datasets were fused for training, 1 dataset was held out as an external validation set. Optimal feature-subset and hyperparameters for each model were adjusted based on a 2,000-resample bootstrap-based internal validation via exhaustive search and grid search. The performance of each model was then tested on the external validation set. RESULTS The Support Vector Machine (SVM) model showed the highest predictive accuracy compared to other methods, with an AUC of 0.82 and an accuracy of 75.7%. Age, sex, disease duration, and preoperative JOA score were identified as the most commonly selected features by both the ML and statistical models. Grid search optimization for hyperparameters successfully enhanced the predictive performance of each ML model, and the SVM model still had the best performance with an AUC of 0.93 and an accuracy of 86.4%. CONCLUSIONS Overall, the study demonstrated that ML classifiers such as SVM can effectively predict surgical outcomes for patients with DCM while identifying associated predictors in a multivariate manner.
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Affiliation(s)
- Jiajun Song
- Department of Orthopedic Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Jie Li
- Department of Minimally Invasive Spine Surgery, Tianjin Hospital, Tianjin 300211, China
| | - Rui Zhao
- Department of Orthopedic Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xu Chu
- Department of Orthopedic Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, China.
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Pfender N, Rosner J, Zipser CM, Friedl S, Schubert M, Sutter R, Klarhoefer M, Spirig JM, Betz M, Freund P, Farshad M, Curt A, Hupp M. Increased cranio-caudal spinal cord oscillations are the cardinal pathophysiological change in degenerative cervical myelopathy. Front Neurol 2023; 14:1217526. [PMID: 38020663 PMCID: PMC10663304 DOI: 10.3389/fneur.2023.1217526] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 10/16/2023] [Indexed: 12/01/2023] Open
Abstract
Introduction Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic incomplete spinal cord injury, but its pathophysiology is poorly understood. As spinal cord compression observed in standard MRI often fails to explain a patient's status, new diagnostic techniques to assess DCM are one of the research priorities. Minor cardiac-related cranio-caudal oscillations of the cervical spinal cord are observed by phase-contrast MRI (PC-MRI) in healthy controls (HCs), while they become pathologically increased in patients suffering from degenerative cervical myelopathy. Whether transversal oscillations (i.e., anterior-posterior and right-left) also change in DCM patients is not known. Methods We assessed spinal cord motion simultaneously in all three spatial directions (i.e., cranio-caudal, anterior-posterior, and right-left) using sagittal PC-MRI and compared physiological oscillations in 18 HCs to pathological changes in 72 DCM patients with spinal canal stenosis. The parameter of interest was the amplitude of the velocity signal (i.e., maximum positive to maximum negative peak) during the cardiac cycle. Results Most patients suffered from mild DCM (mJOA score 16 (14-18) points), and the majority (68.1%) presented with multisegmental stenosis. The spinal canal was considerably constricted in DCM patients in all segments compared to HCs. Under physiological conditions in HCs, the cervical spinal cord oscillates in the cranio-caudal and anterior-posterior directions, while right-left motion was marginal [e.g., segment C5 amplitudes: cranio-caudal: 0.40 (0.27-0.48) cm/s; anterior-posterior: 0.18 (0.16-0.29) cm/s; right-left: 0.10 (0.08-0.13) cm/s]. Compared to HCs, DCM patients presented with considerably increased cranio-caudal oscillations due to the cardinal pathophysiologic change in non-stenotic [e.g., segment C5 amplitudes: 0.79 (0.49-1.32) cm/s] and stenotic segments [.g., segment C5 amplitudes: 0.99 (0.69-1.42) cm/s]). In contrast, right-left [e.g., segment C5 amplitudes: non-stenotic segment: 0.20 (0.13-0.32) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] and anterior-posterior oscillations [e.g., segment C5 amplitudes: non-stenotic segment: 0.26 (0.15-0.45) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] remained on low magnitudes comparable to HCs. Conclusion Increased cranio-caudal oscillations of the cervical cord are the cardinal pathophysiologic change and can be quantified using PC-MRI in DCM patients. This study addresses spinal cord oscillations as a relevant biomarker reflecting dynamic mechanical cord stress in DCM patients, potentially contributing to a loss of function.
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Affiliation(s)
- Nikolai Pfender
- Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
- University Spine Center Zurich, Balgrist University Hospital, Zurich, Switzerland
| | - Jan Rosner
- Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
- Department of Neurology, University Hospital Bern, Inselspital, Bern, Switzerland
| | - Carl M. Zipser
- Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
- University Spine Center Zurich, Balgrist University Hospital, Zurich, Switzerland
| | - Susanne Friedl
- Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
- University Spine Center Zurich, Balgrist University Hospital, Zurich, Switzerland
| | - Martin Schubert
- Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
- University Spine Center Zurich, Balgrist University Hospital, Zurich, Switzerland
| | - Reto Sutter
- Radiology, Balgrist University Hospital, Zurich, Switzerland
| | | | - José M. Spirig
- University Spine Center Zurich, Balgrist University Hospital, Zurich, Switzerland
| | - Michael Betz
- University Spine Center Zurich, Balgrist University Hospital, Zurich, Switzerland
| | - Patrick Freund
- Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
| | - Mazda Farshad
- University Spine Center Zurich, Balgrist University Hospital, Zurich, Switzerland
| | - Armin Curt
- Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
- University Spine Center Zurich, Balgrist University Hospital, Zurich, Switzerland
| | - Markus Hupp
- Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland
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Schmidt TP, Jütten K, Bertram U, Brandenburg LO, Pufe T, Delev D, Gombert A, Mueller CA, Clusmann H, Blume C. Blood spinal cord barrier disruption recovers in patients with degenerative cervical myelopathy after surgical decompression: a prospective cohort study. Sci Rep 2023; 13:7389. [PMID: 37149638 PMCID: PMC10164176 DOI: 10.1038/s41598-023-34004-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 04/22/2023] [Indexed: 05/08/2023] Open
Abstract
The pathophysiology of degenerative cervical myelopathy (DCM) is characterized by chronic compression-induced damage to the spinal cord leading to secondary harm such as disruption of the blood spinal cord barrier (BSCB). It is therefore the purpose of this study to analyze BSCB disruption in pre- and postoperative DCM patients and to correlate those with the clinical status and postoperative outcome. This prospectively controlled cohort included 50 DCM patients (21 female; 29 male; mean age: 62.9 ± 11.2 years). As neurological healthy controls, 52 (17 female; 35 male; mean age 61.8 ± 17.3 years) patients with thoracic abdominal aortic aneurysm (TAAA) and indication for open surgery were included. All patients underwent a neurological examination and DCM-associated scores (Neck Disability Index, modified Japanese Orthopaedic Association Score) were assessed. To evaluate the BSCB status, blood and cerebrospinal fluid (CSF) samples (lumbar puncture or CSF drainage) were taken preoperatively and in 15 DCM patients postoperatively (4 female; 11 male; mean age: 64.7 ± 11.1 years). Regarding BSCB disruption, CSF and blood serum were examined for albumin, immunoglobulin (Ig) G, IgA and IgM. Quotients for CSF/serum were standardized and calculated according to Reiber diagnostic criteria. Significantly increased preoperative CSF/serum quotients were found in DCM patients as compared to control patients: AlbuminQ (p < .001), IgAQ (p < .001) and IgGQ (p < .001). IgMQ showed no significant difference (T = - 1.15, p = .255). After surgical decompression, neurological symptoms improved in DCM patients, as shown by a significantly higher postoperative mJOA compared to the preoperative score (p = .001). This neurological improvement was accompanied by a significant change in postoperative CSF/serum quotients for Albumin (p = .005) and IgG (p = .004) with a trend of a weak correlation between CSF markers and neurological recovery. This study further substantiates the previous findings, that a BSCB disruption in DCM patients is evident. Interestingly, surgical decompression appears to be accompanied by neurological improvement and a reduction of CSF/serum quotients, implying a BSCB recovery. We found a weak association between BSCB recovery and neurological improvement. A BSCB disruption might be a key pathomechanism in DCM patients, which could be relevant to treatment and clinical recovery.
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Affiliation(s)
- Tobias Philip Schmidt
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
| | - Kerstin Jütten
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Ulf Bertram
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Lars Ove Brandenburg
- Institute of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany
| | - Thomas Pufe
- Institute of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany
| | - Daniel Delev
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Alexander Gombert
- Department of Vascular Surgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | | | - Hans Clusmann
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Christian Blume
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
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Zhang JK, Jayasekera D, Song C, Greenberg JK, Javeed S, Dibble CF, Blum J, Sun P, Song SK, Ray WZ. Diffusion Basis Spectrum Imaging Provides Insights Into Cervical Spondylotic Myelopathy Pathology. Neurosurgery 2023; 92:102-109. [PMID: 36519861 PMCID: PMC10158908 DOI: 10.1227/neu.0000000000002183] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 08/11/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Diffusion basis spectrum imaging (DBSI) is a noninvasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments. OBJECTIVE To determine the utility of DBSI as a biomarker of CSM disease severity. METHODS A single-center prospective cohort study enrolled 50 patients with CSM and 20 controls from 2018 to 2020. All patients underwent clinical evaluation and diffusion-weighted MRI, followed by diffusion tensor imaging and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra-axonal changes by isotropic restricted and nonrestricted fraction. Including an intra-axonal diffusion compartment, DBSI improves estimations of axonal injury through intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using modified Japanese Orthopedic Association classifications. Imaging parameters were compared among patient groups using independent samples t tests and ANOVA. RESULTS Twenty controls, 27 mild (modified Japanese Orthopedic Association 15-17), 12 moderate (12-14), and 11 severe (0-11) patients with CSM were enrolled. Diffusion tensor imaging and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and patients with CSM ( P < .05). DBSI fiber fraction, restricted fraction, and nonrestricted fraction were significantly different between groups ( P < .01). DBSI intra-axonal axial diffusivity was lower in mild compared with moderate (mean difference [95% CI]: 1.1 [0.3-2.1], P < .01) and severe (1.9 [1.3-2.4], P < .001) CSM. CONCLUSION DBSI offers granular data on white matter tract integrity in CSM that provide novel insights into disease pathology, supporting its potential utility as a biomarker of CSM disease progression.
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Affiliation(s)
- Justin K. Zhang
- Department of Neurological Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Dinal Jayasekera
- Department of Biomedical Engineering, Washington University in St. Louis McKelvey School of Engineering, Saint Louis, Missouri, USA
| | - Chunyu Song
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Jacob K. Greenberg
- Department of Neurological Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Saad Javeed
- Department of Neurological Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Christopher F. Dibble
- Department of Neurological Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Jacob Blum
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Peng Sun
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Sheng-Kwei Song
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Wilson Z. Ray
- Department of Neurological Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA
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9
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Lee SY, Schmit BD, Kurpad SN, Budde MD. Acute Magnetic Resonance Imaging Predictors of Chronic Motor Function and Tissue Sparing in Rat Cervical Spinal Cord Injury. J Neurotrauma 2022; 39:1727-1740. [PMID: 35708112 PMCID: PMC9734017 DOI: 10.1089/neu.2022.0034] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Predicting functional outcomes from spinal cord injury (SCI) at the acute setting is important for patient management. This work investigated the relationship of early magnetic resonance imaging (MRI) biomarkers in a rat model of cervical contusion SCI with long-term functional outcome and tissue sparing. Forty rats with contusion injury at C5 at either the spinal cord midline (bilateral) or over the lateral cord (unilateral) were examined using in vivo multi-modal quantitative MRI at 1 day post-injury. The extent of T2-weighted hyperintensity reflecting edema was greater in the bilateral model compared with the unilateral injury. Diffusion tensor imaging (DTI) exhibited microscopic damage in similar regions of the cord as reductions in fractional anisotropy (FA) and mean diffusivity (MD), but DTI parameter maps were also confounded by the presence of vasogenic edema that locally increased FA and MD. In comparison, filtered diffusion-weighted imaging (fDWI) more clearly delineated the location of acute axonal damage without effects of vasogenic edema. Pairwise correlation analysis revealed that 28-day motor functional outcomes were most strongly associated with the extent of edema (R = -0.69). Principal component analysis identified close associations of motor functional score with tissue sparing, the extent of edema, lesion area, and injury type (unilateral or bilateral). Among the diffusion MRI parameters, lesion areas measured with fDWI had the strongest association with functional outcome (R = -0.41). Voxelwise correlation analysis identified a locus of white matter damage associated with function in the dorsal white matter, although this was likely driven by variance across the two injury patterns (unilateral and bilateral injury). Nonetheless, correlation with motor function within the damaged region found in the voxelwise analysis outperformed morphological lesion area measurement as a predictor of chronic function. Collectively, this study characterized anatomical and diffusion MRI signatures of acute SCI at cervical spine and their association with chronic functional outcomes and histological results.
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Affiliation(s)
- Seung-Yi Lee
- Neuroscience Doctoral Program, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Department of Biophysics Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Brian D. Schmit
- Department of Biomedical Engineering, Marquette University and Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Shekar N. Kurpad
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Matthew D. Budde
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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10
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Yang HE, Kim WT, Kim DH, Kim SW, Yoo WK. Utility of Diffusion and Magnetization Transfer MRI in Cervical Spondylotic Myelopathy: A Pilot Study. Diagnostics (Basel) 2022; 12:diagnostics12092090. [PMID: 36140491 PMCID: PMC9497906 DOI: 10.3390/diagnostics12092090] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/26/2022] [Accepted: 08/28/2022] [Indexed: 11/16/2022] Open
Abstract
Diffusion tensor imaging (DTI) and magnetization transfer (MT) magnetic resonance imaging (MRI) can help detect spinal cord pathology, and tract-specific analysis of their parameters, such as fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), radial diffusivity (RD) and MT ratio (MTR), can give microstructural information. We performed the tract-based acquisition of MR parameters of three major motor tracts: the lateral corticospinal (CS), rubrospinal (RuS) tract, and lateral reticulospinal (RS) tract as well as two major sensory tracts, i.e., the fasciculus cuneatus (FC) and spinal lemniscus, to detect pathologic change and find correlations with clinical items. MR parameters were extracted for each tract at three levels: the most compressed lesion level and above and below the lesion. We compared the MR parameters of eight cervical spondylotic myelopathy patients and 12 normal controls and analyzed the correlation between clinical evaluation items and MR parameters in patients. RuS and lateral RS showed worse DTI parameters at the lesion level in patients compared to the controls. Worse DTI parameters in those tracts were correlated with weaker power grasp at the lesion level. FC and lateral CS showed a correlation between higher RD and lower FA and MTR with a weaker lateral pinch below the lesion level.
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Affiliation(s)
- Hea-Eun Yang
- Department of Rehabilitation Medicine, VHS Medical Center, Seoul 05368, Korea
| | - Wan-Tae Kim
- Department of Radiology, VHS Medical Center, Seoul 05368, Korea
| | - Dae-Hyun Kim
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Seok-Woo Kim
- Department of Orthopaedic Surgery, Hallym University Sacred Heart Hospital, Anyang 14068, Korea
| | - Woo-Kyoung Yoo
- Department of Physical Medicine and Rehabilitation, Hallym University Sacred Heart Hospital, Anyang 14068, Korea
- Correspondence:
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11
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Pfender N, Rosner J, Zipser CM, Friedl S, Vallotton K, Sutter R, Klarhoefer M, Schubert M, Betz M, Spirig JM, Seif M, Hubli M, Freund P, Farshad M, Curt A, Hupp M. Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy. J Neuroimaging 2022; 32:1121-1133. [PMID: 35962464 PMCID: PMC9805009 DOI: 10.1111/jon.13035] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 07/27/2022] [Accepted: 07/27/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND AND PURPOSE The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup. METHODS Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p < .001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: -0.12 ± 0.30 cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23 cm/second at C2; maximum -0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results. CONCLUSIONS This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression).
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Affiliation(s)
- Nikolai Pfender
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Jan Rosner
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland,Department of NeurologyBern University HospitalInselspitalUniversity of BernBernSwitzerland
| | - Carl Moritz Zipser
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Susanne Friedl
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Kevin Vallotton
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Reto Sutter
- RadiologyBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | | | - Martin Schubert
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Michael Betz
- University Spine Centre ZurichBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - José Miguel Spirig
- University Spine Centre ZurichBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Maryam Seif
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland,Department of NeurophysicsMax Planck Institute for Human Cognitive and Brain SciencesLeipzigGermany
| | - Michèle Hubli
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Patrick Freund
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Mazda Farshad
- University Spine Centre ZurichBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Armin Curt
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland,University Spine Centre ZurichBalgrist University HospitalUniversity of ZurichZurichSwitzerland
| | - Markus Hupp
- Spinal Cord Injury CenterBalgrist University HospitalUniversity of ZurichZurichSwitzerland
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12
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Hupp M, Pfender N, Vallotton K, Rosner J, Friedl S, Zipser CM, Sutter R, Klarhöfer M, Spirig JM, Betz M, Schubert M, Freund P, Farshad M, Curt A. The Restless Spinal Cord in Degenerative Cervical Myelopathy. AJNR Am J Neuroradiol 2021; 42:597-609. [PMID: 33541903 DOI: 10.3174/ajnr.a6958] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 10/12/2020] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE The spinal cord is subject to a periodic, cardiac-related movement, which is increased at the level of a cervical stenosis. Increased oscillations may exert mechanical stress on spinal cord tissue causing intramedullary damage. Motion analysis thus holds promise as a biomarker related to disease progression in degenerative cervical myelopathy. Our aim was characterization of the cervical spinal cord motion in patients with degenerative cervical myelopathy. MATERIALS AND METHODS Phase-contrast MR imaging data were analyzed in 55 patients (37 men; mean age, 56.2 [SD,12.0] years; 36 multisegmental stenoses) and 18 controls (9 men, P = .368; mean age, 62.2 [SD, 6.5] years; P = .024). Parameters of interest included the displacement and motion pattern. Motion data were pooled on the segmental level for comparison between groups. RESULTS In patients, mean craniocaudal oscillations were increased manifold at any level of a cervical stenosis (eg, C5 displacement: controls [n = 18], 0.54 [SD, 0.16] mm; patients [n = 29], monosegmental stenosis [n = 10], 1.86 [SD, 0.92] mm; P < .001) and even in segments remote from the level of the stenosis (eg, C2 displacement: controls [n = 18], 0.36 [SD, 0.09] mm; patients [n = 52]; stenosis: C3, n = 21; C4, n = 11; C5, n = 18; C6, n = 2; 0.85 [SD, 0.46] mm; P < .001). Motion at C2 differed with the distance to the next stenotic segment and the number of stenotic segments. The motion pattern in most patients showed continuous spinal cord motion throughout the cardiac cycle. CONCLUSIONS Patients with degenerative cervical myelopathy show altered spinal cord motion with increased and ongoing oscillations at and also beyond the focal level of stenosis. Phase-contrast MR imaging has promise as a biomarker to reveal mechanical stress to the cord and may be applicable to predict disease progression and the impact of surgical interventions.
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Affiliation(s)
- M Hupp
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.)
| | - N Pfender
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.)
| | - K Vallotton
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.)
| | - J Rosner
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.).,Department of Neurology (J.R.), University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland
| | - S Friedl
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.)
| | - C M Zipser
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.)
| | | | - M Klarhöfer
- Siemens Healthcare AG (M.K.), Zurich, Switzerland
| | - J M Spirig
- University Spine Center Zurich (J.M.S., M.B., M.F., A.C.), Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - M Betz
- University Spine Center Zurich (J.M.S., M.B., M.F., A.C.), Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - M Schubert
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.)
| | - P Freund
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.)
| | - M Farshad
- University Spine Center Zurich (J.M.S., M.B., M.F., A.C.), Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - A Curt
- From the Spinal Cord Injury Center (M.H., N.P., K.V., J.R., S.F., C.M.Z., M.S., P.F., A.C.).,University Spine Center Zurich (J.M.S., M.B., M.F., A.C.), Balgrist University Hospital, University of Zurich, Zurich, Switzerland
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13
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Blume C, Geiger MF, Müller M, Clusmann H, Mainz V, Kalder J, Brandenburg LO, Mueller CA. Decreased angiogenesis as a possible pathomechanism in cervical degenerative myelopathy. Sci Rep 2021; 11:2497. [PMID: 33510227 PMCID: PMC7843718 DOI: 10.1038/s41598-021-81766-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 01/07/2021] [Indexed: 01/03/2023] Open
Abstract
Endogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.
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Affiliation(s)
- Christian Blume
- Department of Neurosurgery, RWTH Aachen University, Pauwelstrasse 30, 52074, Aachen, Germany.
| | - M F Geiger
- Department of Neurosurgery, RWTH Aachen University, Pauwelstrasse 30, 52074, Aachen, Germany
| | - M Müller
- Department of Neuroradiology, RWTH Aachen University, Pauwelstrasse 30, 52074, Aachen, Germany
| | - H Clusmann
- Department of Neurosurgery, RWTH Aachen University, Pauwelstrasse 30, 52074, Aachen, Germany
| | - V Mainz
- Department of Medical Psychology and Medical Sociology, RWTH Aachen University, Pauwelsstrasse 19, 52074, Aachen, Germany
| | - J Kalder
- Department of Vascular Surgery, Gießen University, Rudolf-Buchheim-str. 7, 35392, Gießen, Germany
| | - L O Brandenburg
- Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057, Rostock, Germany
| | - C A Mueller
- Department of Neurosurgery, RWTH Aachen University, Pauwelstrasse 30, 52074, Aachen, Germany
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14
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Shea GKH, Koljonen PA, Chan YS, Cheung KMC. Prospects of cell replacement therapy for the treatment of degenerative cervical myelopathy. Rev Neurosci 2020; 32:275-287. [PMID: 33661584 DOI: 10.1515/revneuro-2020-0075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 10/03/2020] [Indexed: 11/15/2022]
Abstract
Degenerative cervical myelopathy (DCM) presents insidiously during middle-age with deterioration in neurological function. It accounts for the most common cause of non-traumatic spinal cord injury in developed countries and disease prevalence is expected to rise with the aging population. Whilst surgery can prevent further deterioration, biological therapies may be required to restore neurological function in advanced disease. Cell replacement therapy has been inordinately focused on treatment of traumatic spinal cord injury yet holds immense promise in DCM. We build upon this thesis by reviewing the pathophysiology of DCM as revealed by cadaveric and molecular studies. Loss of oligodendrocytes and neurons occurs via apoptosis. The tissue microenvironment in DCM prior to end-stage disease is distinct from that following acute trauma, and in many ways more favourable to receiving exogenous cells. We highlight clinical considerations for cell replacement in DCM such as selection of cell type, timing and method of delivery, as well as biological treatment adjuncts. Critically, disease models often fail to mimic features of human pathology. We discuss directions for translational research towards clinical application.
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Affiliation(s)
- Graham Ka Hon Shea
- Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China
| | - Paul Aarne Koljonen
- Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China
| | - Ying Shing Chan
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Kenneth Man Chee Cheung
- Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China
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15
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Jiao G, Li Z, Zhou P, Yang J, Li X. Clinical outcomes of epidural and intradural decompression for treatment of degenerative cervical myelopathy. J Int Med Res 2020; 48:300060520929585. [PMID: 32527182 PMCID: PMC7294486 DOI: 10.1177/0300060520929585] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Objective This study was performed to examine the clinical outcomes of epidural and intradural decompression for degenerative cervical myelopathy. Methods The data for 13 patients who underwent epidural and intradural decompression for treatment of degenerative cervical myelopathy (study group) and 20 patients who underwent only cervical laminoplasty, fusion, and epidural decompression (historical control group) were retrospectively reviewed. The preoperative and postoperative neurological status was evaluated using the Japanese Orthopaedic Association (JOA) score. Results All patients’ neurological symptoms were significantly improved at the final follow-up. In the study group, the patients’ mean preoperative JOA score was 8.07 ± 1.80, and the final score improved by 70.88% ± 21.18%. The blood loss and operation time were significantly greater in the study group than control group. The recovery time was shorter in the study group than control group. The improvement rate was not significantly different between the two groups. Conclusions A pia mater incision with separation of the arachnoid adhesion can significantly improve the cerebrospinal fluid flow and spinal blood flow in degenerative cervical myelopathy. Arachnoid adhesion can lead to intradural spinal scar compression. The surgical intervention described herein can achieve satisfactory neurological outcomes and shorten the recovery time.
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Affiliation(s)
- Genlong Jiao
- Department of Orthopaedics, the First Affiliated Hospital of Jinan University, Huangpu Avenue West Road, Guangzhou, PR China
| | - Zhizhong Li
- Department of Orthopaedics, the First Affiliated Hospital of Jinan University, Huangpu Avenue West Road, Guangzhou, PR China
| | - Pan Zhou
- Department of Orthopaedics, the First Affiliated Hospital of Jinan University, Huangpu Avenue West Road, Guangzhou, PR China
| | - Jinpei Yang
- Department of Orthopaedics, the First Affiliated Hospital of Jinan University, Huangpu Avenue West Road, Guangzhou, PR China
| | - Xueshi Li
- Department of Orthopaedics, the First Affiliated Hospital of Jinan University, Huangpu Avenue West Road, Guangzhou, PR China
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16
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Khan DZ, Khan MS, Kotter MR, Davies BM. Tackling Research Inefficiency in Degenerative Cervical Myelopathy: Illustrative Review. JMIR Res Protoc 2020; 9:e15922. [PMID: 32525490 PMCID: PMC7317636 DOI: 10.2196/15922] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 09/23/2019] [Accepted: 09/23/2019] [Indexed: 01/01/2023] Open
Abstract
Background Degenerative cervical myelopathy (DCM) is widely accepted as the most common cause of adult myelopathy worldwide. Despite this, there is no specific term or diagnostic criteria in the International Classification of Diseases 11th Revision and no Medical Subject Headings (MeSH) or an equivalent in common literature databases. This makes searching the literature and thus conducting systematic reviews or meta-analyses imprecise and inefficient. Efficient research synthesis is integral to delivering evidence-based medicine and improving research efficiency. Objective This study aimed to illustrate the difficulties encountered when attempting to carry out a comprehensive and accurate evidence search in the field of DCM by identifying the key sources of imprecision and quantifying their impact. Methods To identify the key sources of imprecision and quantify their impact, an illustrative search strategy was developed using a validated DCM hedge combined with contemporary strategies used by authors in previous systematic reviews and meta-analyses. This strategy was applied to Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE) databases looking for relevant DCM systematic reviews and meta-analyses published within the last 5 years. Results The MEDLINE via PubMed search strategy returned 24,166 results, refined to 534 papers after the application of inclusion and exclusion criteria. Of these, 32.96% (176/534) results were about DCM, and 18.16% (97/534) of these were DCM systematic reviews or meta-analyses. Non-DCM results were organized into imprecision categories (spinal: 268/534, 50.2%; nonspinal: 84/534, 15.5%; and nonhuman: 8/534, 1.5%). The largest categories were spinal cord injury (75/534, 13.67%), spinal neoplasms (44/534, 8.24%), infectious diseases of the spine and central nervous system (18/534, 3.37%), and other spinal levels (ie, thoracic, lumbar, and sacral; 18/534, 3.37%). Counterintuitively, the use of human and adult PubMed filters was found to exclude a large number of relevant articles. Searching a second database (EMBASE) added an extra 12 DCM systematic reviews or meta-analyses. Conclusions DCM search strategies face significant imprecision, principally because of overlapping and heterogenous search terms, and inaccurate article indexing. Notably, commonly employed MEDLINE filters, human and adult, reduced search sensitivity, whereas the related articles function and the use of a second database (EMBASE) improved it. Development of a MeSH labeling and a standardized DCM definition would allow comprehensive and specific indexing of DCM literature. This is required to support a more efficient research synthesis.
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Affiliation(s)
- Danyal Zaman Khan
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Muhammad Shuaib Khan
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Mark Rn Kotter
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.,Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge, United Kingdom
| | - Benjamin Marshall Davies
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
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A comprehensive finite element model of surgical treatment for cervical myelopathy. Clin Biomech (Bristol, Avon) 2020; 74:79-86. [PMID: 32145673 DOI: 10.1016/j.clinbiomech.2020.02.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 02/09/2020] [Accepted: 02/13/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cervical myelopathy is a common and debilitating chronic spinal cord dysfunction. Treatment includes anterior and/or posterior surgical intervention to decompress the spinal cord and stabilize the spine, but no consensus has been made as to the preferable surgical intervention. The objective of this study was to develop an finite element model of the healthy and myelopathic C2-T1 cervical spine and common anterior and posterior decompression techniques to determine how spinal cord stress and strain is altered in healthy and diseased states. METHODS A finite element model of the C2-T1 cervical spine, spinal cord, pia, dura, cerebral spinal fluid, and neural ligaments was developed and validated against in vivo human displacement data. To model cervical myelopathy, disc herniation and osteophytes were created at the C4-C6 levels. Three common surgical interventions were then incorporated at these levels. FINDINGS The finite element model accurately predicted healthy and myelopathic spinal cord displacement compared to motions observed in vivo. Spinal cord strain increased during extension in the cervical myelopathy finite element model. All surgical techniques affected spinal cord stress and strain. Specifically, adjacent levels had increased stress and strain, especially in the anterior cervical discectomy and fusion case. INTERPRETATIONS This model is the first biomechanically validated, finite element model of the healthy and myelopathic C2-T1 cervical spine and spinal cord which predicts spinal cord displacement, stress, and strain during physiologic motion. Our findings show surgical intervention can cause increased strain in the adjacent levels of the spinal cord which is particularly worse following anterior cervical discectomy and fusion.
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Blume C, Geiger MF, Brandenburg LO, Müller M, Mainz V, Kalder J, Albanna W, Clusmann H, Mueller CA. Patients with degenerative cervical myelopathy have signs of blood spinal cord barrier disruption, and its magnitude correlates with myelopathy severity: a prospective comparative cohort study. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2020; 29:986-993. [PMID: 31982957 DOI: 10.1007/s00586-020-06298-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 01/02/2020] [Accepted: 01/15/2020] [Indexed: 11/25/2022]
Abstract
PURPOSE The aim of this study is to detect the presence of blood spinal cord barrier (BSCB) disruption in patients with degenerative cervical myelopathy (DCM). METHODS In this prospective non-randomized controlled cohort study, 28 patients with DCM were prospectively included. All patients had indication for neurosurgical decompression. Furthermore, 38 controls with thoracic abdominal aortic aneurysm (TAAA) and indication for surgery were included. All patients underwent neurological examination. Regarding BSCB disruption and intrathecal immunoglobulin (Ig) concentrations, cerebrospinal fluid (CSF) and blood serum were examined for albumin, IgG, IgA and IgM. Quotients (Q) (CSF/serum) were standardized and calculated according to Reibers' diagnostic criteria. RESULTS Patients and controls distinguished significantly in their clinical status. AlbuminQ, as expression of BSCB disruption, was significantly increased in the DCM patients compared to the controls. Quotients of IgG and IgA differed significantly between the groups as an expression of intrathecal diffusion. In the subgroup analysis of patients with mild/moderate clinical status of myelopathy and patients with severe clinical status, the disruption of the BSCB was significantly increased with clinical severity. Likewise, IgAQ and IgGQ presented increased quotients related to the clinical severity of myelopathy. CONCLUSION In this study, we detected an increased permeability and disruption of the BSCB in DCM patients. The severity of BSCB disruption and the diffusion of Ig are related to the clinical status in our patient cohort. Having documented this particular pathomechanism in patients with DCM, we suggest that this diagnostic tool cloud be an important addition to surgical decision making in the future. These slides can be retrieved under Electronic Supplementary Material.
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Affiliation(s)
- Christian Blume
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
| | - Matthias Florian Geiger
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Lars Ove Brandenburg
- Institute of Anatomy and Cell Biology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Marguerite Müller
- Department of Neuroradiology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Verena Mainz
- Department of Medical Psychology and Medical Sociology, RWTH Aachen University, Pauwelsstrasse 19, 52074, Aachen, Germany
| | - Johannes Kalder
- Department of Vascular Surgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Walid Albanna
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Hans Clusmann
- Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
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Degenerative cervical myelopathy - update and future directions. Nat Rev Neurol 2020; 16:108-124. [PMID: 31974455 DOI: 10.1038/s41582-019-0303-0] [Citation(s) in RCA: 281] [Impact Index Per Article: 56.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2019] [Indexed: 11/09/2022]
Abstract
Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults worldwide. DCM encompasses various acquired (age-related) and congenital pathologies related to degeneration of the cervical spinal column, including hypertrophy and/or calcification of the ligaments, intervertebral discs and osseous tissues. These pathologies narrow the spinal canal, leading to chronic spinal cord compression and disability. Owing to the ageing population, rates of DCM are increasing. Expeditious diagnosis and treatment of DCM are needed to avoid permanent disability. Over the past 10 years, advances in basic science and in translational and clinical research have improved our understanding of the pathophysiology of DCM and helped delineate evidence-based practices for diagnosis and treatment. Surgical decompression is recommended for moderate and severe DCM; the best strategy for mild myelopathy remains unclear. Next-generation quantitative microstructural MRI and neurophysiological recordings promise to enable quantification of spinal cord tissue damage and help predict clinical outcomes. Here, we provide a comprehensive, evidence-based review of DCM, including its definition, epidemiology, pathophysiology, clinical presentation, diagnosis and differential diagnosis, and non-operative and operative management. With this Review, we aim to equip physicians across broad disciplines with the knowledge necessary to make a timely diagnosis of DCM, recognize the clinical features that influence management and identify when urgent surgical intervention is warranted.
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Stoner KE, Abode-Iyamah KO, Magnotta VA, Howard MA, Grosland NM. Measurement of in vivo spinal cord displacement and strain fields of healthy and myelopathic cervical spinal cord. J Neurosurg Spine 2019; 31:53-59. [PMID: 30901756 DOI: 10.3171/2018.12.spine18989] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Accepted: 12/05/2018] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Cervical myelopathy (CM) is a common and debilitating form of spinal cord injury caused by chronic compression; however, little is known about the in vivo mechanics of the healthy spinal cord during motion and how these mechanics are altered in CM. The authors sought to measure 3D in vivo spinal cord displacement and strain fields from MR images obtained during physiological motion of healthy individuals and cervical myelopathic patients. METHODS Nineteen study participants, 9 healthy controls and 10 CM patients, were enrolled in the study. All study participants had 3T MR images acquired of the cervical spine in neutral, flexed, and extended positions. Displacement and strain fields and corresponding principal strain were obtained from the MR images using image registration. RESULTS The healthy spinal cord displaces superiorly in flexion and inferiorly in extension. Principal strain is evenly distributed along the spinal cord. The CM spinal cord displaces less than the healthy cord and the magnitude of principal strain is higher, at the midcervical levels. CONCLUSIONS Increased spinal cord compression during cervical myelopathy limits motion of the spinal cord and increases spinal cord strain during physiological motion. Future studies are needed to investigate how treatment, such as surgical intervention, affects spinal cord mechanics.
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Affiliation(s)
- Kirsten E Stoner
- 1Department of Biomedical Engineering, The University of Iowa, and
| | | | | | | | - Nicole M Grosland
- 1Department of Biomedical Engineering, The University of Iowa, and
- 4Orthopedics and Rehabilitation, The University of Iowa Hospitals and Clinics, Iowa City, Iowa
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Expression profile of long non-coding RNAs in cervical spondylotic myelopathy of rats by microarray and bioinformatics analysis. Genomics 2019; 111:1192-1200. [PMID: 30615923 DOI: 10.1016/j.ygeno.2019.01.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Revised: 12/21/2018] [Accepted: 01/03/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION It has been reported that a wide range of long non-coding RNAs (lncRNAs) are implicated in numerous diseases such as tumor, cardiopathy and neurological disorders. Identifying the differentially expressed (DE) profile of lncRNAs in cervical spondylotic myelopathy (CSM) is essential to understand the mechanisms of CSM. METHODS Microarray assay, quantitative real-time PCR (qRT-PCR) and bioinformatics analysis were employed to reveal the DE profile and potential functions of lncRNAs in CSM. RESULTS Microarray analysis displayed the DE profiles of lncRNAs and mRNAs in rats between the CSM group and the control (CON) group. Thereinto, 1266 DE lncRNAs (738 up-regulation and 528 down-regulation) and 847 mRNAs (487 up-regulation and 360 down-regulation) with >1.1 fold change (FC) were finally identified. Moreover, 17 lncRNAs (13 up-regulation and 4 down-regulation) and 18 mRNAs (13 up-regulation and 5 down-regulation) were found deregulated by >2 FC. Further bioinformatics analysis showed the most remarkable biological processes among up-regulated RNAs contain cellular response to interferon-beta, inflammatory response and innate immune response, which may involve in CSM. Besides, related DE mRNAs of 17 DE lncRNAs in the genome were related to signaling pathway about NOD-like receptor, TNF, and apoptosis. In addition, a co-expression network of lncRNA-mRNA was established for analyzing the biological roles of lncRNAs. Among these, we found a ceRNA network related to CSM. Finally, the expressions of the DE lncRNAs and ceRNA network confirmed by qRT-PCR were in agreement with microarray data. CONCLUSIONS Our study revealed the DE profiles of lncRNAs and mRNAs for CSM. Those dysregulated RNAs may represent potential therapeutic targets of CSM for further study.
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Tykocki T, du Plessis J, Wynne-Jones G. Correlation between the severity of myelopathy and cervical morphometric parameters on dynamic magnetic resonance imaging. Acta Neurochir (Wien) 2018; 160:1251-1258. [PMID: 29687255 DOI: 10.1007/s00701-018-3540-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 04/04/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND To compare morphometric factors of cervical spine in the cervical stenosis on dynamic and static magnetic resonance imaging. To analyse the relationship between the severity of myelopathy and morphometric parameters. METHODS Patients with cervical canal stenosis scanned with MRI in neutral (N), flexion (F) and extension (E) positions were retrospectively reviewed. All cases were evaluated in Nurick and Muhle grades. Following parameters were measured: anterior and posterior length of the cervical cord (aLCC, pLCC), mid-cord distance (L value), cervical cord angle (CCA), cervical lordosis, spine/cord (S/C) angle ratio, spinal cord (SC) area, cerebrospinal fluid (CSF) area, and CSF reserve ratio (CSF/CSF plus SC). Univariate multiple regression for Nurick grade as dependent factor was used. RESULTS Sixty-three patients and 34 men, with the mean age of 58.2 ± 11 years, were analysed. Significant differences were found for pLCC, SC area, C lordosis and CCA. The difference between F and E for C lordosis angle was 42.80° ± 14.4 and for CC angle 30.42° ± 9.6. The mean S/C angle ratio was calculated for 1.4 ± 1.3. Nurick grade positively correlated with age (p = 0.041) and S/C angle ratio (p = 0.011), negatively with SC area (p = 0.006) and flexion-extension difference of L value (0.004). CONCLUSIONS Severity of myelopathy correlates with age, spinal cord area on extension and reduced mobility of spinal cord. An association between spine/cervical cord angle mismatch and Nurick grade was found.
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Affiliation(s)
- Tomasz Tykocki
- Department of Musculoskeletal, Spinal Unit, Royal Victoria Infirmary, Queen Victoria Rd, Newcastle upon Tyne, NE1 4LP, UK.
| | - Johannes du Plessis
- Department of Neuroradiology, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - Guy Wynne-Jones
- Department of Musculoskeletal, Spinal Unit, Royal Victoria Infirmary, Queen Victoria Rd, Newcastle upon Tyne, NE1 4LP, UK
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Gibson J, Nouri A, Krueger B, Lakomkin N, Nasser R, Gimbel D, Cheng J. Degenerative Cervical Myelopathy: A Clinical Review. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 2018; 91:43-48. [PMID: 29599656 PMCID: PMC5872640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Degenerative Cervical Myelopathy (DCM) is the most common form of spinal cord impairment in adults and results in disability and reduced quality of life. DCM can present with a wide set of clinical and imaging findings, including: 1) pain and reduced range of motion of the neck, and motor and sensory deficits on clinical exam, and 2) cord compression due to static and dynamic injury mechanisms resulting from degenerative changes of the bone, ligaments, and intervertebral discs on MRI. The incidence and prevalence of DCM has been estimated at a minimum of 4.1 and 60.5 per 100,000, respectively, but surgical trends and an aging population suggest these numbers will rise in the future. The diagnosis of DCM is based on clinical examination, with a positive Hoffmann's sign and hand numbness typically appearing in the upper limbs, and gait abnormalities such as difficulty with tandem gait serving as sensitive diagnostic findings. Loss of bladder function may also occur in patients with severe DCM. The degree of neurological impairment can be measured using the modified Japanese Association Scale (mJOA) or Nurick grade. Non-operative management has a limited role in the treatment, while surgical management has been shown to both be safe and effective for halting disease progression and improving neurological function. Predictors of surgical outcome include age and baseline severity, indicating that early recognition of DCM is important for ensuring an optimal surgical outcome.
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Affiliation(s)
- Justin Gibson
- Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Aria Nouri
- Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH,Department of Neurosurgery, Yale University School of Medicine, New Haven, CT
| | - Bryan Krueger
- Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Nikita Lakomkin
- Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY
| | - Rani Nasser
- Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - David Gimbel
- Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Joseph Cheng
- Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH,Department of Neurosurgery, Yale University School of Medicine, New Haven, CT,To whom all correspondence should be addressed: Joseph S. Cheng MD, MS, FAANS, FACS, Professor and Chairman, Department of Neurosurgery, Frank H. Mayfield Chair of Neurosurgery, University of Cincinnati College of Medicine, 260 Stetson Street, Suite 2200 Cincinnati, Ohio, 45219
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Lin WS, Huang TF, Chuang TY, Lin CL, Kao CH. Association between Cervical Spondylosis and Migraine: A Nationwide Retrospective Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15040587. [PMID: 29587400 PMCID: PMC5923629 DOI: 10.3390/ijerph15040587] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 03/22/2018] [Accepted: 03/22/2018] [Indexed: 12/16/2022]
Abstract
Background: Few studies have investigated the longitudinal association between cervical spondylosis (CS) and migraine by using a nationwide population-based database. Methods: We conducted a retrospective cohort study from 2000 to 2011 identifying 27,930 cases of cervical spondylosis and 111,720 control subjects (those without cervical spondylosis) from a single database. The subjects were frequency-matched on the basis of sex, age, and diagnosis date. The non- cervical spondylosis cohort was four times the size of the cervical spondylosis cohort. To quantify the effects of cervical spondylosis on the risk of migraine, univariate and multivariate Cox proportional hazard regression analyses were used to calculate the hazard ratio (HR), and 95% confidence interval (CI). Results: After a 10-year follow-up controlling for potential confounding factors, overall migraine incidence was higher in the cervical spondylosis cohort than in the non-cervical spondylosis cohort (5.16 and 2.09 per 1000 people per year, respectively; crude hazard ratio = 2.48, 95% confidence interval = 2.28-2.69), with an adjusted hazard ratio of 2.03 (95% confidence interval = 1.86-2.22) after accounting for sex, age, comorbidities, and medication. Individuals with myelopathy in the cervical spondylosis cohort had a 2.19 times (95% confidence interval = 1.80-2.66) higher incidence of migraine when compared than did those in the non- cervical spondylosis cohort. Conclusions: Individuals with cervical spondylosis exhibited a higher risk of migraine than those without cervical spondylosis. The migraine incidence rate was even higher among individuals with cervical spondylotic myelopathy.
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Affiliation(s)
- Wang-Sheng Lin
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
| | - Tung-Fu Huang
- Department of Surgery, Faculty of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
- Department of Orthopaedics & Traumatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
| | - Tien-Yow Chuang
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung 404, Taiwan.
- College of Medicine, China Medical University, Taichung 404, Taiwan.
| | - Chia-Hung Kao
- Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan.
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung 404, Taiwan.
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413, Taiwan.
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Craciunas SC, Gorgan MR, Ianosi B, Lee P, Burris J, Cirstea CM. Remote motor system metabolic profile and surgery outcome in cervical spondylotic myelopathy. J Neurosurg Spine 2017; 26:668-678. [PMID: 28304238 DOI: 10.3171/2016.10.spine16479] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE In patients with cervical spondylotic myelopathy (CSM), the motor system may undergo progressive functional/structural changes rostral to the lesion, and these changes may be associated with clinical disability. The extent to which these changes have a prognostic value in the clinical recovery after surgical treatment is not yet known. In this study, magnetic resonance spectroscopy (MRS) was used to test 2 primary hypotheses. 1) Based on evidence of corticospinal and spinocerebellar, rubro-, or reticulospinal tract degeneration/dysfunction during chronic spinal cord compression, the authors hypothesized that the metabolic profile of the primary motor cortices (M1s) and cerebellum, respectively, would be altered in patients with CSM, and these alterations would be associated with the extent of the neurological disabilities. 2) Considering that damage and/or plasticity in the remote motor system may contribute to clinical recovery, they hypothesized that M1 and cerebellar metabolic profiles would predict, at least in part, surgical outcome. METHODS The metabolic profile, consisting of N-acetylaspartate (NAA; marker of neuronal integrity), myoinositol (glial marker), choline (cell membrane synthesis and turnover), and glutamate-glutamine (glutamatergic system), of the M1 hand/arm territory in each hemisphere and the cerebellum vermis was investigated prior to surgery in 21 patients exhibiting weakness of the upper extremities and/or gait abnormalities. Age- and sex-matched controls (n = 16) were also evaluated to estimate the pre-CSM metabolic profile of these areas. Correlation and regression analyses were performed between preoperative metabolite levels and clinical status 6 months after surgery. RESULTS Relative to controls, patients exhibited significantly higher levels of choline but no difference in the levels of other metabolites across M1s. Cerebellar metabolite levels were indistinguishable from control levels. Certain metabolites-myo-inositol and choline across M1s, NAA and glutamate-glutamine in the left M1, and myo-inositol and glutamate-glutamine in the cerebellum-were significantly associated with postoperative clinical status. These associations were greatly improved by including preoperative clinical metrics into the models. Likewise, these models improved the predictive value of preoperative clinical metrics alone. CONCLUSIONS These preliminary findings demonstrate relationships between the preoperative metabolic profiles of two remote motor areas and surgical outcome in CSM patients. Including preoperative clinical metrics in the models significantly strengthened the predictive value. Although further studies are needed, this investigation provides an important starting point to understand how the changes upstream from the injury may influence the effect of spinal cord decompression.
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Affiliation(s)
- Sorin C Craciunas
- Department of Neurosurgery, Bagdasar-Arseni Hospital, Bucharest, Romania
| | - Mircea R Gorgan
- Department of Neurosurgery, Bagdasar-Arseni Hospital, Bucharest, Romania
| | - Bogdan Ianosi
- Department of Neurology, Elbe Kliniken Hospital, University Medical Center Hamburg-Eppendorf, Germany.,Romanian National Institute of Neurology and Neurovascular Diseases, Bucharest, Romania
| | - Phil Lee
- Departments of 4 Molecular and Integrative Physiology and
| | - Joseph Burris
- Department of Physical Medicine & Rehabilitation, University of Missouri, Columbia, Missouri
| | - Carmen M Cirstea
- Neurology, Kansas University Medical Center, Kansas City, Kansas; and.,Department of Physical Medicine & Rehabilitation, University of Missouri, Columbia, Missouri
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Abstract
STUDY DESIGN A prospective cohort study. OBJECTIVE In this study, we employed diffusion basis spectrum imaging (DBSI) to quantitatively assess axon/myelin injury, cellular inflammation, and axonal loss of cervical spondylotic myelopathy (CSM) spinal cords. SUMMARY OF BACKGROUND DATA A major shortcoming in the management of CSM is the lack of an effective diagnostic approach to stratify treatments and to predict outcomes. No current clinical diagnostic imaging approach is capable of accurately reflecting underlying spinal cord pathologies. METHODS Seven patients with mild (mJOA ≥15), five patients with moderate (14≥mJOA ≥11), and two patients with severe (mJOA <11) CSM were prospectively enrolled. Given the low number of severe patients, moderate and severe patients were combined for comparison with seven age-matched controls and statistical analysis. We employed the newly developed DBSI to quantitatively measure axon and myelin injury, cellular inflammation, and axonal loss. RESULTS Median DBSI-inflammation volume is similar in control (266 μL) and mild CSM (171 μL) subjects, with a significant overlap of the middle 50% of observations (quartile 3 - quartile 1). This was in contrast to moderate CSM subjects that had higher DBSI-inflammation volumes (382 μL; P = 0.033). DBSI-axon volume shows a strong correlation with clinical measures (r = 0.79 and 0.87, P = 1.9 x 10-5 and 2 x 10-4 for mJOA and MDI, respectively). In addition to axon and myelin injury, our findings suggest that both inflammation and axon loss contribute to neurological impairment. Most strikingly, DBSI-derived axon volume declines as severity of impairment increases. CONCLUSION DBSI-quantified axonal loss may be an imaging biomarker to predict functional recovery following decompression in CSM. Our results demonstrate an increase of about 60% in the odds of impairment relative to the control for each decrease of 100 μL in axon volume. LEVEL OF EVIDENCE 3.
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27
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Dolan RT, Butler JS, O’Byrne JM, Poynton AR. Mechanical and cellular processes driving cervical myelopathy. World J Orthop 2016; 7:20-9. [PMID: 26807352 PMCID: PMC4716567 DOI: 10.5312/wjo.v7.i1.20] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 10/12/2015] [Accepted: 11/03/2015] [Indexed: 02/06/2023] Open
Abstract
Cervical myelopathy is a well-described clinical syndrome that may evolve from a combination of etiological mechanisms. It is traditionally classified by cervical spinal cord and/or nerve root compression which varies in severity and number of levels involved. The vast array of clinical manifestations of cervical myelopathy cannot fully be explained by the simple concept that a narrowed spinal canal causes compression of the cord, local tissue ischemia, injury and neurological impairment. Despite advances in surgical technology and treatment innovations, there are limited neuro-protective treatments for cervical myelopathy, which reflects an incomplete understanding of the pathophysiological processes involved in this disease. The aim of this review is to provide a comprehensive overview of the key pathophysiological processes at play in the development of cervical myelopathy.
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Wang C, Tian F, Zhou Y, He W, Cai Z. The incidence of cervical spondylosis decreases with aging in the elderly, and increases with aging in the young and adult population: a hospital-based clinical analysis. Clin Interv Aging 2016; 11:47-53. [PMID: 26834465 PMCID: PMC4716725 DOI: 10.2147/cia.s93118] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background and purpose Cervical spondylosis is well accepted as a common degenerative change in the cervical spine. Compelling evidence has shown that the incidence of cervical spondylosis increases with age. However, the relationship between age and the incidence of cervical spondylosis remains obscure. It is essential to note the relationship between age and the incidence of cervical spondylosis through more and more clinical data. Methods In the case-controlled study reported here, retrospective clinical analysis of 1,276 cases of cervical spondylosis has been conducted. We analyzed the general clinical data, the relationship between age and the incidence of cervical spondylosis, and the relationship between age-related risk factors and the incidence of cervical spondylosis. A chi-square test was used to analyze the associations between different variables. Statistical significance was defined as a P-value of less than 0.05. Results The imaging examination demonstrated the most prominent characteristic features of cervical spondylosis: bulge or herniation at C3-C4, C4-C5, and C5-C6. The incidence of cervical spondylosis increased with aging before age 50 years and decreased with aging after age 50 years, especially in the elderly after 60 years old. The occurrence rate of bulge or herniation at C3-C4, C4-C5, C5-C6, and C6-C7 increased with aging before age 50 years and decreased with aging after age 50 years, especially after 60 years. Moreover, the incidence of hyperosteogeny and spinal stenosis increased with aging before age 60 years and decreased with aging after age 60 years, although there was no obvious change in calcification. The age-related risk factors, such as hypertension, hyperlipidemia, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking, have no relationship with the incidence of cervical spondylosis. Conclusion A decreasing proportion of cervical spondylosis with aging occurs in the elderly, while the proportion of cervical spondylosis increases with aging in the young and the adults. This investigation implicates that aging is not only a contributor to the clinical performance of cervical spondylosis in the elderly, although the incidence of cervical spondylosis is proportional to the progress of age.
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Affiliation(s)
- Chuanling Wang
- Department of Neurology, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, People's Republic of China
| | - Fuming Tian
- Department of Neurology, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, People's Republic of China
| | - Yingjun Zhou
- Physical Examination Center, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, People's Republic of China
| | - Wenbo He
- Department of Neurology, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, People's Republic of China
| | - Zhiyou Cai
- Department of Neurology, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, People's Republic of China
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Song H, Fang X, Wen M, Yu F, Gao K, Sun C, Wang Z. Role of MK2 signaling pathway in the chronic compression of cervical spinal cord. Am J Transl Res 2015; 7:2355-2363. [PMID: 26807183 PMCID: PMC4697715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 10/13/2015] [Indexed: 06/05/2023]
Abstract
OBJECTIVE In this study, chronic compression of cervical spinal cord was introduced into twy/twy mice and the role of MK2 signaling pathway was investigated in this disease. METHODS twy/twy mice aged 6-24 weeks were used and the inflammatory response in the cervical spinal cord was observed. The Institute of Cancer Research (ICR) mice were used as controls. MK2 inhibitor (PF-3644022, 30 mg/kg) was administered intragastrically to twy/twy mice. The motor behavior was firstly observed in these three groups by Catwalk gait analysis. And the cervical spinal cord between C2 and C3 of vertebral segments was analyzed by MRI and Western blot assay. RESULTS The stride length of paws and interlimb coordination reduced in twy/twy mice. However, at 4 weeks after PF-3644022 treatment, a marked improvement was observed in the motor function. The expressions of inflammation related factors (such as IL-1β, NF-κB, TNF-α, MK2 and p-MK2) and apoptosis related proteins (such as cleaved caspase-8 and bax/bcl-2) in the spinal cord of twy/twy mice significantly increased as compared to controls, but 4-week treatment with PF-3644022 markedly reduced the expressions of these factors and apoptotic proteins in the cervical spinal cord. CONCLUSION MK2 signaling pathway is involved in the chronic compression induced inflammation of the cervical spinal cord. Thus, to inhibit the MK2 pathway may used to improve the outcome and prevent the deterioration of neurological dysfunction.
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Affiliation(s)
- Hongxing Song
- Department of Orthopaedics Surgery, Beijing Shijitan Hospital, Capital Medical University, The Ninth Clinical Medical College of Peking UniversityBeijing 100038, China
| | - Xiutong Fang
- Department of Orthopaedics Surgery, Beijing Shijitan Hospital, Capital Medical University, The Ninth Clinical Medical College of Peking UniversityBeijing 100038, China
| | - Mingjie Wen
- Department of Immunology, School of Basic Medical Sciences, Capital Medical UniversityBeijing 100069, China
| | - Fang Yu
- Department of Orthopaedics Surgery, Beijing Shijitan Hospital, Capital Medical University, The Ninth Clinical Medical College of Peking UniversityBeijing 100038, China
| | - Kai Gao
- Institute of Laboratory Animal Sciences, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing, 100021, China
| | - Chenli Sun
- Department of Orthopaedics Surgery, Beijing Shijitan Hospital, Capital Medical University, The Ninth Clinical Medical College of Peking UniversityBeijing 100038, China
| | - Zhenwei Wang
- Department of Orthopaedics Surgery, Beijing Shijitan Hospital, Capital Medical University, The Ninth Clinical Medical College of Peking UniversityBeijing 100038, China
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Abstract
STUDY DESIGN Review. OBJECTIVE To formally introduce "degenerative cervical myelopathy" (DCM) as the overarching term to describe the various degenerative conditions of the cervical spine that cause myelopathy. Herein, the epidemiology, pathogenesis, and genetics of conditions falling under this hypernym are carefully described. SUMMARY OF BACKGROUND DATA Nontraumatic, degenerative forms of cervical myelopathy represent the commonest cause of spinal cord impairment in adults and include cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and degenerative disc disease. Unfortunately, there is neither a specific term nor a specific diagnostic International Classification of Diseases, Tenth Revision code to describe this collection of clinical entities. This has resulted in the inconsistent use of diagnostic terms when referring to patients with myelopathy due to degenerative disease of the cervical spine. METHODS Narrative review. RESULTS The incidence and prevalence of myelopathy due to degeneration of the spine are estimated at a minimum of 41 and 605 per million in North America, respectively. Incidence of cervical spondylotic myelopathy-related hospitalizations has been estimated at 4.04/100,000 person-years, and surgical rates seem to be rising. Pathophysiologically, myelopathy results from static compression, spinal malalignment leading to altered cord tension and vascular supply, and dynamic injury mechanisms. Occupational hazards, including transportation of goods by weight bearing on top of the head, and other risk factors may accelerate DCM development. Potential genetic factors include those related to MMP-2 and collagen IX for degenerative disc disease, and collagen VI and XI for ossification of the posterior longitudinal ligament. In addition, congenital anomalies including spinal stenosis, Down syndrome, and Klippel-Feil syndrome may predispose to the development of DCM. CONCLUSION Although DCMs can present as separate diagnostic entities, they are highly interrelated, frequently manifest concomitantly, present similarly from a clinical standpoint, and seem to be in part a response to compensate and improve stability due to progressive age and wear of the cervical spine. The use of the term "degenerative cervical myelopathy" is advocated. LEVEL OF EVIDENCE 5.
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Jay Gaffney C, Ryan Spiker W. Treating multilevel (three or four level) cervical myelopathy with ACDF or ACCF. ACTA ACUST UNITED AC 2014. [DOI: 10.1053/j.semss.2014.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Abstract
Cervical spondylotic myelopathy (CSM) is the leading cause of myelopathy in patients over age 50 years. Despite advances, CSM remains a clinical diagnosis and its natural history remains unclear. The treatment of CSM is controversial, especially in patients with mild or moderate clinical disease without rapid progression of symptoms. Herein, we begin with a clinical vignette followed by a brief description of the clinical problems. We discuss evaluation, treatment, and recommendations for the treatment of CSM. Emphasis is drawn to areas of uncertainty and present level of evidence for the treatment modalities of CSM.
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Affiliation(s)
- Ehab Shiban
- Neurosurgery Department, Klinikum rechts der Isar, Technical University Munich, Germany
| | - Bernhard Meyer
- Neurosurgery Department, Klinikum rechts der Isar, Technical University Munich, Germany
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Abstract
STUDY DESIGN This study is a combination of narrative and systematic review. OBJECTIVE Clinicians who deal with cervical spondylotic myelopathy (CSM) should be up-to-date with the emerging knowledge related to the cascade of pathobiological secondary events that take place under chronic cervical spinal cord compression. Moreover, by performing a systematic review, we aim to (1) describe the natural history and (2) determine potential risk factors that affect the progression of CSM. SUMMARY OF BACKGROUND DATA The pathophysiology, natural history, as well as the factors associated with clinical deterioration have not been fully described in CSM. METHODS For the first part of the study, a literature review was performed. To answer key questions 1 and 2 of the second goal, a systematic search was conducted in PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 7, 2012. We included all articles that described the progression and outcomes of CSM for which no surgical intervention was given. RESULTS By performing a narrative literature review, we found that the assumption that acute traumatic spinal cord injury and CSM share a similar series of cellular and molecular secondary injury events was made in the past. However, recent advances in basic research have shown that the chronic mechanical compression results in secondary injury mechanisms that have distinct characteristics regarding the nature and the temporal profile compared with those of spinal cord injury. For the purpose of the systematic review, 10 studies yielding 16 publications met inclusion criteria for key questions 2 and 3. Moderate-strength evidence related to the natural history of CSM suggests that 20% to 60% of patients will deteriorate neurologically over time without surgical intervention. Finally, there is low-strength evidence indicating that the area of circumferential compression is associated with deteriorating neurological symptoms. CONCLUSION CSM has unique pathobiological mechanisms that mainly remain unexplored. Although the natural history of CSM can be mixed, surgical intervention eliminates the chances of the neurological deterioration. EVIDENCE-BASED CLINICAL RECOMMENDATIONS: RECOMMENDATION Evidence concerning the natural history of CSM suggests that 20% to 60% of patients will deteriorate neurologically over time without surgical intervention. Therefore, we recommend that patients with mild CSM be counseled regarding the natural history of CSM and have the option of surgical decompression explained. OVERALL STRENGTH OF EVIDENCE Moderate. STRENGTH OF RECOMMENDATION Strong. SUMMARY STATEMENTS: Chronic compression of the spinal cord results in progressive neural cell loss related to secondary mechanisms including apoptosis, neuroinflammation, and vascular disruption.
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Floeth FW, Galldiks N, Eicker S, Stoffels G, Herdmann J, Steiger HJ, Antoch G, Rhee S, Langen KJ. Hypermetabolism in 18F-FDG PET Predicts Favorable Outcome Following Decompressive Surgery in Patients with Degenerative Cervical Myelopathy. J Nucl Med 2013; 54:1577-83. [DOI: 10.2967/jnumed.112.113183] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Eicker SO, Langen KJ, Galldiks N, Stoffels G, Herdmann J, Steiger HJ, Floeth FW. Clinical value of 2-deoxy-[18F]fluoro-d-glucose positron emission tomography in patients with cervical spondylotic myelopathy. Neurosurg Focus 2013; 35:E2. [DOI: 10.3171/2013.3.focus1379] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Cervical spondylotic myelopathy (CSM) is one of the most common spinal cord disorders in the elderly. It is usually diagnosed by MRI, but in a significant number of patients the clinical course of CSM does not correlate with the extent of the spinal cord compression. Recent studies have suggested that a distinct metabolic pattern of the cervical cord, as assessed by PET with 2-deoxy-[18F]fluoro-d-glucose (18F-FDG) may predict a patient's clinical outcome after decompressive surgery for cervical spine stenosis. The authors provide an overview of the recent literature regarding the value of PET with 18F-FDG of the cervical cord in patients with CSM, paying attention to prognostic aspects and the potential role of inflammatory processes in the acute phase of the disease.
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Affiliation(s)
- Sven O. Eicker
- 1Department of Neurosurgery, University of Düsseldorf
- 5Department of Neurosurgery, University of Hamburg-Eppendorf, Germany
| | | | - Norbert Galldiks
- 2Institute of Neuroscience and Medicine, Research Center Jülich
- 3Department of Neurology, University of Cologne
| | | | - Jörg Herdmann
- 4Department of Spine and Pain, St.-Vinzenz-Hospital, Düsseldorf; and
| | | | - Frank W. Floeth
- 1Department of Neurosurgery, University of Düsseldorf
- 4Department of Spine and Pain, St.-Vinzenz-Hospital, Düsseldorf; and
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Karadimas SK, Moon ES, Yu WR, Satkunendrarajah K, Kallitsis JK, Gatzounis G, Fehlings MG. A novel experimental model of cervical spondylotic myelopathy (CSM) to facilitate translational research. Neurobiol Dis 2013; 54:43-58. [PMID: 23466695 DOI: 10.1016/j.nbd.2013.02.013] [Citation(s) in RCA: 99] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Revised: 02/01/2013] [Accepted: 02/19/2013] [Indexed: 12/15/2022] Open
Abstract
Cervical spondylotic myelopathy (CSM) is the most common form of spinal cord impairment in adults. However critical gaps in our knowledge of the pathobiology of this disease have limited therapeutic advances. To facilitate progress in the field of regenerative medicine for CSM, we have developed a unique, clinically relevant model of CSM in rats. To model CSM, a piece of synthetic aromatic polyether, to promote local calcification, was implanted microsurgically under the C6 lamina in rats. We included a sham group in which the material was removed 30s after the implantation. MRI confirmed postero-anterior cervical spinal cord compression at the C6 level. Rats modeling CSM demonstrated insidious development of a broad-based, ataxic, spastic gait, forelimb weakness and sensory changes. No neurological deficits were noted in the sham group during the course of the study. Spasticity of the lower extremities was confirmed by a significantly greater H/M ratio in CSM rats in H reflex recordings compared to sham. Rats in the compression group experienced significant gray and white matter loss, astrogliosis, anterior horn cell loss and degeneration of the corticospinal tract. Moreover, chronic progressive posterior compression of the cervical spinal cord resulted in compromise of the spinal cord microvasculature, blood-spinal cord barrier disruption, inflammation and activation of apoptotic signaling pathways in neurons and oligodendrocytes. Finally, CSM rats were successfully subjected to decompressive surgery as confirmed by MRI. In summary, this novel rat CSM model reproduces the chronic and progressive nature of human CSM, produces neurological deficits and neuropathological features accurately mimicking the human condition, is MRI compatible and importantly, allows for surgical decompression.
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Affiliation(s)
- Spyridon K Karadimas
- Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada
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Kalsi-Ryan S, Karadimas SK, Fehlings MG. Cervical spondylotic myelopathy: the clinical phenomenon and the current pathobiology of an increasingly prevalent and devastating disorder. Neuroscientist 2012. [PMID: 23204243 DOI: 10.1177/1073858412467377] [Citation(s) in RCA: 282] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Cervical spondylotic myelopathy (CSM) is a common disorder involving chronic progressive compression of the cervical spinal cord due to degenerative disc disease, spondylosis, or other degenerative pathology. CSM is the most common form of spinal cord impairment and causes functional decline leading to reduced independence and quality of life. Despite a sound understanding of the disease process, clinical presentation and management, a universal definition of CSM and a standardized index of severity are not currently used universally. Work is required to develop a definition and establish clinical predictors of progression to improve management of CSM. Despite advances in decompressive and reconstructive surgery, patients are often left with residual disability. Gaps in knowledge of the pathobiology of CSM have limited therapeutic advances to complement surgery. Although the histopathologic and pathophysiologic similarities between CSM and traumatic spinal cord injury have long been acknowledged, the unique pathomechanisms of CSM remain unexplored. Increased efforts to elucidate CSM pathobiology could lead to the discovery of novel therapeutic targets for human CSM and other spinal cord diseases. Here, the natural history of CSM, epidemiology, clinical presentation, and current methods of clinical management are reported, along with the current state of basic scientific research in the field.
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