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Rujeedawa T, Mowforth OD, Brannigan J, Magee J, Francis JJ, Laing RJ, Davies BM, Kotter MR. A single centre service evaluation of degenerative cervical and thoracic myelopathy. J Clin Neurosci 2023; 117:168-172. [PMID: 37826868 DOI: 10.1016/j.jocn.2023.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/23/2023] [Accepted: 10/06/2023] [Indexed: 10/14/2023]
Abstract
BACKGROUND Degenerative cervical myelopathy (DCM) and degenerative thoracic myelopathy (DTM) present with leg, bladder and bowel symptoms. If imaging confirms spinal cord compression both conditions are usually managed surgically. Surgical timing is important in patient management as it affects post-operative recovery and long-term outcomes. This service evaluation aims to explore whether that patients with DTM are more likely to be treated urgently than those with DCM and to examine whether any differences in management are justified. METHODS A retrospective service evaluation was registered and approved by the Cambridge University Hospitals NHS Foundation Trust (CUH) Clinical Audit Department (Clinical Project ID4455 PRN10455). All patients who had undergone surgery for DTM at CUH from January 2015 until April 2022 were included. Comparison was made to a cohort of DCM patients who underwent surgery at CUH from June 2016 to January 2019. Data analysis was conducted in R. RESULTS A total of 130 DCM patients and 78 DTM patients were included. Our DCM and DTM patient cohorts had comparable demographics, but DTM patients had fewer spinal levels affected. Despite equivalent disease severity, DTM patients had a shorter time to diagnosis, shorter wait for surgery and were more likely to be operated on as an emergency case. CONCLUSIONS Despite comparable demographics and pathophysiology, DTM was diagnosed and managed more quickly than DCM. Better defined diagnostic pathways for degenerative spinal myelopathy may hold opportunities to optimise diagnosis and management, ensuring consistent high quality, efficient and equitable care.
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Affiliation(s)
- Tanzil Rujeedawa
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Oliver D Mowforth
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
| | - Jamie Brannigan
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Joe Magee
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Jibin J Francis
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Rodney J Laing
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Benjamin M Davies
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Mark R Kotter
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
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Jin JY, Yu M, Xu RF, Sun Y, Li BH, Zhou FF. Risk Factors for Cerebrospinal Fluid Leakage After Extradural Spine Surgery: A Meta-Analysis and Systematic Review. World Neurosurg 2023; 179:e269-e280. [PMID: 37625633 DOI: 10.1016/j.wneu.2023.08.075] [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: 08/08/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023]
Abstract
BACKGROUND Cerebrospinal fluid (CSF) leakage is 1 of the common complications of spine surgery and is largely caused by intraoperative or postoperative dural tears. Associations of different factors with postoperative CSF leakage have not been consistent. In this study we aimed to identify demographic, disease-related, and surgical risk factors for CSF leakage after extradural spine surgery in a systematic review and meta-anlysis. METHODS The PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Wanfang data, Chinese Weipu Database, and SinoMed databases were searched from inception until October 24, 2022. Fixed-effects or random-effects models were used to calculate odds ratios and 95% confidence intervals. The quality of observational studies was evaluated using the Newcastle-Ottawa scale instrument. RESULTS A total of 15 observational studies with 1,719,923 participants were included in this systematic review. All studies had a Newcastle-Ottawa scale score greater than or equal to 6. Age older than 70 years, smoking, ossification of the posterior longitudinal ligament, adhesion of spinal dura, spinal canal stenosis, cervical fracture, spondylolisthesis, revision surgery, and multiple surgical segments were all related to CSF leakage in the pooled analysis. Obesity and disease duration>1 year were not associated with the leakage of CSF. CONCLUSIONS This study will provide a reference for the identification of patients at high risk of developing CSF leakage, which suggests clinicians to strengthen the observation of drainage fluid in high-risk groups.
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Affiliation(s)
- Ji-Yan Jin
- Department of Orthopedic Surgery, Peking University Third Hospital, Beijing, PR China
| | - Miao Yu
- Department of Nursing, Peking University Third Hospital, Beijing, PR China
| | - Rui-Feng Xu
- Department of Orthopedic Surgery, Peking University Third Hospital, Beijing, PR China
| | - Yu Sun
- Department of Orthopedic Surgery, Peking University Third Hospital, Beijing, PR China
| | - Bao-Hua Li
- Department of Neurology, Peking University Third Hospital, Beijing, PR China
| | - Fei-Fei Zhou
- Department of Orthopedic Surgery, Peking University Third Hospital, Beijing, PR China.
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Shlykov MA, Giles EM, Kelly MP, Lin SJ, Pham VT, Saccone NL, Yanik EL. Evaluation of Genetic and Nongenetic Risk Factors for Degenerative Cervical Myelopathy. Spine (Phila Pa 1976) 2023; 48:1117-1126. [PMID: 37249397 PMCID: PMC10524420 DOI: 10.1097/brs.0000000000004735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 05/15/2023] [Indexed: 05/31/2023]
Abstract
STUDY DESIGN Cohort study. OBJECTIVE We aimed to evaluate the associations of genetic and nongenetic factors with degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA There is mounting evidence for an inherited predisposition for DCM, but uncertainty remains regarding specific genetic markers involved. Similarly, nongenetic factors are thought to play a role. MATERIALS AND METHODS Using diagnosis codes from hospital records linked to the UK Biobank cohort, patients with cervical spondylosis were identified followed by the identification of a subset with DCM. Nongenetic variables evaluated included age, sex, race, Townsend deprivation index, body mass index, occupational demands, osteoporosis, and smoking. Genome-wide association analyses were conducted using logistic regression adjusted for age, sex, population principal components, and follow-up. RESULTS A total of 851 DCM cases out of 2787 cervical spondylosis patients were identified. Several nongenetic factors were independently associated with DCM including age [odds ratio (OR)=1.11, 95% CI=1.01-1.21, P =0.024], male sex (OR=1.63, 95% CI=1.37-1.93, P <0.001), and relative socioeconomic deprivation (OR=1.03, 95% CI=1.00-1.06, P =0.030). Asian race was associated with lower DCM risk (OR=0.44, 95% CI=0.22-0.85, P =0.014). We did not identify genome-wide significant (≤5×10 -8 ) single-nucleotide polymorphisms (SNPs) associated with DCM. The strongest genome-wide signals were at SNP rs67256809 in the intergenic region of the genes LINC02582 and FBXO15 on chromosome 18 ( P =1.12×10 -7 ) and rs577081672 in the GTPBP1 gene on chromosome 22 ( P =2.9×10 -7 ). No SNPs reported in prior DCM studies were significant after adjusting for replication attempts. CONCLUSIONS Increasing age, male sex, and relative socioeconomic deprivation were identified as independent risk factors for DCM, whereas Asian race was inversely associated. SNPs of potential interest were identified in GTPBP1 and an intergenic region on chromosome 18, but these associations did not reach genome-wide significance. Identification of genetic and nongenetic DCM susceptibility markers may guide understanding of DCM disease processes, inform risk, guide prevention and potentially inform surgical outcomes. LEVEL OF EVIDENCE Prognostic level III.
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Affiliation(s)
| | | | | | - Shiow J Lin
- Department of Genetics, Washington University School of Medicine, St. Louis, MO
| | | | - Nancy L Saccone
- Department of Genetics, Washington University School of Medicine, St. Louis, MO
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Clinical risk factors associated with the development of adjacent segment disease in patients undergoing ACDF: A systematic review. Spine J 2023; 23:146-156. [PMID: 36031098 DOI: 10.1016/j.spinee.2022.08.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 07/18/2022] [Accepted: 08/17/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND CONTEXT Cervical fusion for degenerative disorders carries a known risk of adjacent segment disease (ASD), a complication that often requires surgical intervention to relieve symptoms. Proposed risk factors for development of ASD include both clinical and radiographic patient characteristics. However, the true impact of these risk factors is less understood due to limitations in sample sizes and loss to follow-up in individual studies. PURPOSE To review and critically examine current literature on the clinical risk factors associated with development of ASD in the cervical spine following ACDF. STUDY DESIGN Systematic Review and Meta-Analysis. METHODS We systematically reviewed the literature in December 2019 according to the PRISMA guidelines. Methodological quality of included papers and quality of evidence were evaluated according to MINORS and GRADE framework. Meta-analysis was performed to compute the odds ratio(OR)with corresponding 95% confidence interval(CI)for dichotomous data, and mean difference(MD) with 95% CI for continuous variables. RESULTS 6,850 records were obtained using database query. Title/abstract screening resulted in 19 articles for full review, from which 10 papers met the criteria for analysis. There were no significant differences in gender (OR 0.99, 95% CI 0.75-1.30), BMI (MD -0.09, 95% CI -0.46 to 0.29), smoking (OR 1.13, 95% CI 0.80-1.59), alcohol (OR 1.07, 95% CI 0.70-1.64), diabetes (OR 0.85, 95% CI 0.56-1.31), number of segments fused (OR 0.86, 95% CI 0.64-1.16), and preoperative JOA (MD -0.50, 95% CI -1.04 to 0.04). Age (MD 3.21, 95% CI 2.00-4.42), congenital/developmental stenosis (OR 1.94, 95% CI 1.06-3.56), preoperative NDI (MD 4.18, 95% CI 2.11 to 6.26), preoperative VAS (neck) (MD 0.54 95% CI 0.09-0.99), and preoperative VAS (arm) (MD 0.98, 95% CI 0.43-1.34) were found to be statistically significant risk factors. CONCLUSION Patients with congenital stenosis, advanced age, and high preoperative NDI are at increased risk of developing ASD.
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Baucher G, Taskovic J, Troude L, Molliqaj G, Nouri A, Tessitore E. Risk factors for the development of degenerative cervical myelopathy: a review of the literature. Neurosurg Rev 2021; 45:1675-1689. [PMID: 34845577 DOI: 10.1007/s10143-021-01698-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 10/19/2021] [Accepted: 11/17/2021] [Indexed: 12/11/2022]
Abstract
Degenerative cervical myelopathy (DCM) encompasses various pathological conditions causing spinal cord (SC) impairment, including spondylosis (multiple level degeneration), degenerative disc disease (DDD), ossification of the posterior longitudinal ligament (OPLL), and ossification of the ligamentum flavum (OLF). It is considered the most common cause of SC dysfunction among the adult population. The degenerative phenomena of DDD, spondylosis, OPLL and OLF, is likely due to both inter-related and distinct factors. Age, cervical alignment, and range of motion, as well as congenital factors such as cervical cord-canal mismatch due to congenital stenosis, Klippel-Feil, Ehler-Danlos, and Down syndromes have been previously reported as potential factors of risk for DCM. The correlation between some comorbidities, such as rheumatoid arthritis and movement disorders (Parkinson disease and cervical dystonia) and DCM, has also been reported; however, the literature remains scare. Other patient-specific factors including smoking, participation in contact sports, regular heavy load carrying on the head, and occupation (e.g. astronauts) have also been suggested as potential risk of myelopathy development. Most of the identified DCM risk factors remain poorly studied however. Further researches will be necessary to strengthen the current knowledge on the subject, especially concerning physical labors in order to identify patients at risk and to develop an effective treatment strategy for preventing this increasing prevalent disorder.
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Affiliation(s)
- Guillaume Baucher
- Neurosurgical Unit, Geneva University Hospital, Geneva, Switzerland.
- AP-HM, Hôpital Universitaire Nord, Neurochirurgie adulte, Chemin Des Bourrely, 13015, Marseille, France.
| | - Jelena Taskovic
- Neurosurgical Unit, Geneva University Hospital, Geneva, Switzerland
| | - Lucas Troude
- AP-HM, Hôpital Universitaire Nord, Neurochirurgie adulte, Chemin Des Bourrely, 13015, Marseille, France
| | - Granit Molliqaj
- Neurosurgical Unit, Geneva University Hospital, Geneva, Switzerland
| | - Aria Nouri
- Neurosurgical Unit, Geneva University Hospital, Geneva, Switzerland
| | - Enrico Tessitore
- Neurosurgical Unit, Geneva University Hospital, Geneva, Switzerland
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Marie-Hardy L, Pascal-Moussellard H. Degenerative cervical myelopathy. Rev Neurol (Paris) 2021; 177:490-497. [PMID: 33781560 DOI: 10.1016/j.neurol.2020.11.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/25/2020] [Accepted: 11/26/2020] [Indexed: 10/21/2022]
Abstract
Degenerative cervical myelopathy (DCM) frequently leads to severe neurologic disability but is still frequently underdiagnosed. One explanation may be the variability of the symptoms presented by the patients, from paresthesia to quadriplegia, making it another great masquerader. What do we know? How can we manage better these patients? We will review the keys points concerning its challenging diagnosis (clinical and radiologic), some of the recent discoveries about DCM, notably the underlying genetic mutations identified, linked to its pathophysiology, before addressing the consensual points concerning its management and the major evolutive risk: acute decompensation.
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Affiliation(s)
- L Marie-Hardy
- Orthopaedic surgery department, Pitié-Salpétrière hospital, 47, boulevard de l'Hôpital, 75013 Paris, France.
| | - H Pascal-Moussellard
- Orthopaedic surgery department, Pitié-Salpétrière hospital, 47, boulevard de l'Hôpital, 75013 Paris, France
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Khurana VG. Adverse impact of smoking on the spine and spinal surgery. Surg Neurol Int 2021; 12:118. [PMID: 33880223 PMCID: PMC8053459 DOI: 10.25259/sni_6_2021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 02/24/2021] [Indexed: 12/15/2022] Open
Abstract
Background Tobacco smokers and companies are well aware that smoking increases the risks for cancers, vascular morbidity, and early mortality. This is a review of the plethora of adverse effects chronic smoking has on spinal tissues and spinal surgery. Methods Medline (PubMed) and Google Scholar databases were searched for pertinent literature through keywords related to smoking, spondylosis, and spinal surgery. Results Smoking accelerates spondylosis by impairing spinal tissue vascular supply through atherosclerosis and thrombosis, while inducing local hypoxia, inflammation, proteolysis, and cell loss. It, thus, compromises disc, cartilage, synovium, bone, and blood vessels. It can lead to early surgery, delayed wound healing, increased surgical site infection, failed fusion, more re-operations, and chronic spinal pain. Conclusion There is ample evidence to support surgeons' declining to operate on chronic smokers. The need for immediate and permanent smoking cessation and its potential benefits should be emphasized for the patient considering or who has undergone spinal surgery.
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Affiliation(s)
- Vini G Khurana
- CNS Neurosurgery, Woolloomooloo, New South Wales, Australia
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Tu J, Vargas Castillo J, Das A, Diwan AD. Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms. J Clin Med 2021; 10:jcm10061214. [PMID: 33804008 PMCID: PMC8001572 DOI: 10.3390/jcm10061214] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/07/2021] [Accepted: 03/09/2021] [Indexed: 12/12/2022] Open
Abstract
Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.
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Affiliation(s)
- Ji Tu
- Spine Labs, St. George and Sutherland Clinical School, University of New South Wales, Kogarah, NSW 2217, Australia; (J.T.); (A.D.D.)
| | | | - Abhirup Das
- Spine Labs, St. George and Sutherland Clinical School, University of New South Wales, Kogarah, NSW 2217, Australia; (J.T.); (A.D.D.)
- Spine Service, St. George Hospital, Kogarah, NSW 2217, Australia;
- Correspondence:
| | - Ashish D. Diwan
- Spine Labs, St. George and Sutherland Clinical School, University of New South Wales, Kogarah, NSW 2217, Australia; (J.T.); (A.D.D.)
- Spine Service, St. George Hospital, Kogarah, NSW 2217, Australia;
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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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Pope DH, Davies BM, Mowforth OD, Bowden AR, Kotter MRN. Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies. J Clin Med 2020; 9:jcm9010282. [PMID: 31968564 PMCID: PMC7019856 DOI: 10.3390/jcm9010282] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 12/20/2019] [Accepted: 01/14/2020] [Indexed: 01/22/2023] Open
Abstract
Degenerative cervical myelopathy (DCM) is estimated to be the most common cause of adult spinal cord impairment. Evidence that is suggestive of a genetic basis to DCM has been increasing over the last decade. A systematic search was conducted in MEDLINE, EMBASE, Cochrane, and HuGENet databases from their origin up to 14th December 2019 to evaluate the role of single genes in DCM in its onset, clinical phenotype, and response to surgical intervention. The initial search yielded 914 articles, with 39 articles being identified as eligible after screening. We distinguish between those contributing to spinal column deterioration and those contributing to spinal cord deterioration in assessing the evidence of genetic contributions to DCM. Evidence regarding a total of 28 candidate genes was identified. Of these, 22 were found to have an effect on the radiological onset of spinal column disease, while 12 genes had an effect on clinical onset of spinal cord disease. Polymorphisms of eight genes were found to have an effect on the radiological severity of DCM, while three genes had an effect on clinical severity. Polymorphisms of six genes were found to have an effect on clinical response to surgery in spinal cord disease. There are clear genetic effects on the development of spinal pathology, the central nervous system (CNS) response to bony pathology, the severity of both bony and cord pathology, and the subsequent response to surgical intervention. Work to disentangle the mechanisms by which the genes that are reviewed here exert their effects, as well as improved quality of evidence across diverse populations is required for further investigating the genetic contribution to DCM.
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Affiliation(s)
- Daniel H. Pope
- School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK
| | - Benjamin M. Davies
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK
| | - Oliver D. Mowforth
- School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK
| | - A. Ramsay Bowden
- Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
- The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, UK
| | - Mark R. N. Kotter
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK
- Anne McLaren Laboratory for Regenerative Medicine, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK
- Correspondence: ; Tel.: +44-122-376-3366
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Role of APOE and IL18RAP gene polymorphisms in cervical spondylotic myelopathy in Indian population. J Clin Neurosci 2019; 66:83-86. [PMID: 31126849 DOI: 10.1016/j.jocn.2019.05.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 03/18/2019] [Accepted: 05/11/2019] [Indexed: 11/24/2022]
Abstract
Cervical spondylotic myelopathy (CSM) is a progressive degenerative spine disease. It is not clear why certain patients develop symptomatic myelopathy whereas others do not, even in the presence of radiographic features of cervical stenosis. Genetic predisposition has been suggested, supported by familial occurrence of CSM. In this study we explored the demographic and radiographic features of CSM in Indian population and studied the association between polymorphisms in interleukin18RAP and apo-lipoprotein genes in CSM. A total of 100 CSM patients and 100 healthy control subjects were included in this study. Genotyping of APOE (rs7412 and rs429358) and IL18RAP (rs1420106 and rs917997) gene polymorphisms was performed by Taqman allelic discrimination assay. Comparison of allelic frequencies, ε2 versus ε3 (OR = 4.4, 95%CI = 1.23-15.73, P = 0.002) and ε2 versus ε4 (OR = 6.67, 95%CI = 1.58-28.04, P = 0.009) showed a statistically significant association for the risk of CSM. There was no significant association between different genotypes with sex, T2 signal intensity change and Nurick grade. Only patients having multiple level cervical prolapsed intervertebral disc (PIVD) on MRI, had a higher proportion of the ε2 allele as compared to controls (p = <0.0001). No significant association was found between IL18RAP gene polymorphisms (rs1420106 and rs917997) with the risk of CSM. ε2 allele was associated with the risk of CSM in Indian population. There was no significant association between the two single nucleotide polymorphisms (SNPs) of IL18RAP gene with risk of CSM.
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Badhiwala JH, Witiw CD, Nassiri F, Jaja BNR, Akbar MA, Mansouri A, Merali Z, Ibrahim GM, Wilson JR, Fehlings MG. Patient phenotypes associated with outcome following surgery for mild degenerative cervical myelopathy: a principal component regression analysis. Spine J 2018; 18:2220-2231. [PMID: 29746963 DOI: 10.1016/j.spinee.2018.05.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 04/04/2018] [Accepted: 05/01/2018] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Predictors of outcome after surgery for degenerative cervical myelopathy (DCM) have been determined previously through hypothesis-driven multivariate statistical models that rely on a priori knowledge of potential confounders, exclude potentially important variables because of restrictions in model building, cannot include highly collinear variables in the same model, and ignore intrinsic correlations among variables. PURPOSE The present study aimed to apply a data-driven approach to identify patient phenotypes that may predict outcomes after surgery for mild DCM. STUDY DESIGN This is a principal component analysis of data from two related prospective, multicenter cohort studies. PATIENT SAMPLE The study included patients with mild DCM, defined by a modified Japanese Orthopaedic Association score of 15-17, undergoing surgical decompression as part of the AOSpine CSM-NA or CSM-I trials. OUTCOME MEASURES Patient outcomes were evaluated preoperatively at baseline and at 6 months, 1 year, and 2 years after surgery. Quality of life (QOL) was evaluated by the Neck Disability Index (NDI) and Short Form-36 version 2 (SF-36v2). These are both patient self-reported measures that evaluate health-related QOL, with NDI being specific to neck conditions and SF-36v2 being a generic instrument. MATERIALS AND METHODS The analysis included 154 patients. A heterogeneous correlation matrix was created using a combination of Pearson, polyserial, and polychoric regressions among 67 variables, which then underwent eigen decomposition. Scores of significant principal components (PCs) (with eigenvalues>1) were included in multivariate logistic regression analyses for three dichotomous outcomes of interest: achievement of the minimum clinically important difference [MCID] in (1) NDI (≤-7.5), (2) SF-36v2 Physical Component Summary (PCS) score (≥5), and (3) SF-36v2 Mental Component Summary (MCS) score (≥5). RESULTS Twenty-four significant PCs accounting for 75% of the variance in the data were identified. Two PCs were associated with achievement of the MCID in NDI. The first (PC 1) was dominated by variables related to surgical approach and number of operated levels; the second (PC 21) consisted of variables related to patient demographics, severity and etiology of DCM, comorbid status, and surgical approach. Both PC 1 and PC 21 also correlated with SF-36v2 PCS score, in addition to PC 4, which described patients' physical profile, including gender, height, and weight, as well as comorbid renal disease; PC 6, which received large loadings from variables related to cardiac disease, impaired mobility, and length of surgery and recovery; and PC 9, which harbored large contributions from features of upper limb dysfunction, cardiorespiratory disease, surgical approach, and region. In addition to PC 21, a component profiling patients' socioeconomic status and support systems and degree of physical disability (PC 24) was associated with achievement of the MCID in SF-36 MCS score. CONCLUSIONS Through a data-driven approach, we identified several phenotypes associated with disability and physical and mental health-related QOL. Such data reduction methods may separate patient-, disease-, and treatment-related variables more accurately into clinically meaningful phenotypes that may inform patient care and recruitment into clinical trials.
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Affiliation(s)
- Jetan H Badhiwala
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8
| | - Christopher D Witiw
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8
| | - Farshad Nassiri
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8
| | - Blessing N R Jaja
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8
| | - Muhammad A Akbar
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8
| | - Alireza Mansouri
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8
| | - Zamir Merali
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8
| | - George M Ibrahim
- Division of Neurosurgery, Department of Surgery, University of Toronto, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8
| | - Jefferson R Wilson
- Division of Neurosurgery, Department of Surgery, University of Toronto, St. Michael's Hospital, 30 Bond St, Toronto, Ontario, Canada M5B 1W8
| | - Michael G Fehlings
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8.
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AL-Bashaireh AM, Haddad LG, Weaver M, Kelly DL, Chengguo X, Yoon S. The Effect of Tobacco Smoking on Musculoskeletal Health: A Systematic Review. JOURNAL OF ENVIRONMENTAL AND PUBLIC HEALTH 2018; 2018:4184190. [PMID: 30112011 PMCID: PMC6077562 DOI: 10.1155/2018/4184190] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 05/30/2018] [Indexed: 12/14/2022]
Abstract
This systematic review explored associations between smoking and health outcomes involving the musculoskeletal system. AMSTAR criteria were followed. A comprehensive search of PubMed, Web of Science, and Science Direct returned 243 articles meeting inclusion criteria. A majority of studies found smoking has negative effects on the musculoskeletal system. In research on bones, smoking was associated with lower BMD, increased fracture risk, periodontitis, alveolar bone loss, and dental implant failure. In research on joints, smoking was associated with increased joint disease activity, poor functional outcomes, and poor therapeutic response. There was also evidence of adverse effects on muscles, tendons, cartilage, and ligaments. There were few studies on the musculoskeletal health outcomes of secondhand smoke, smoking cessation, or other modes of smoking, such as waterpipes or electronic cigarettes. This review found evidence that suggests tobacco smoking has negative effects on the health outcomes of the musculoskeletal system. There is a need for further research to understand mechanisms of action for the effects of smoking on the musculoskeletal system and to increase awareness of healthcare providers and community members of the adverse effects of smoking on the musculoskeletal system.
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Affiliation(s)
| | - Linda G. Haddad
- College of Health and Human Services, University of North Carolina Wilmington, Wilmington, NC, USA
| | - Michael Weaver
- College of Nursing, University of Florida, Gainesville, FL, USA
| | | | - Xing Chengguo
- College of Pharmacy, University of Florida, Gainesville, FL, USA
| | - Saunjoo Yoon
- College of Nursing, University of Florida, Gainesville, FL, USA
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Ganau M, Holly LT, Mizuno J, Fehlings MG. Future Directions and New Technologies for the Management of Degenerative Cervical Myelopathy. Neurosurg Clin N Am 2018; 29:185-193. [DOI: 10.1016/j.nec.2017.09.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Wang G, Cao Y, Wu T, Duan C, Wu J, Hu J, Lu H. Genetic factors of cervical spondylotic myelopathy-a systemic review. J Clin Neurosci 2017; 44:89-94. [PMID: 28734792 DOI: 10.1016/j.jocn.2017.06.043] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 06/19/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Cervical spondylotic myelopathy (CSM) is a degenerative disorder of the neck. Recent studies have reported the roles of single nucleotide polymorphisms and abnormal gene expression in the etiology and development of CSM. However, a systemic review of these findings is currently unavailable. METHODS A systemic review of genetic factors of CSM was conducted through searching PubMed and EMbase databases. A total of 9 studies were included in this study, which included 8 genes: brain derived neurotrophic factor (BDNF), osteopontin (OPN), bone morphogenic protein (BMP) 4, collagen IX, vitamin D receptor (VDR), apolipoprotein E (ApoE), hypoxia-inducible factor α (HIF-1α), and cyclooxygenase 2 (COX-2). RESULTS The polymorphisms of 6 genes (OPN, BMP-4, collagen IX, VDR, HIF-1α) showed significant association with the susceptibility to or risk of CSM. The polymorphisms of 3 genes (BMP-4, ApoE4, HIF-1α) were significantly associated with the postoperative outcome. The polymorphism of BDNF, VDR, and expression of COX-2 were associated with the severity of disease. CONCLUSION This review demonstrates that 8 genes were associated with CSM although there is no repeated study. This review also suggests that large scale and high quality studies are needed to provide more reliable evidence for future evaluation.
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Affiliation(s)
- Guohua Wang
- Department of Spine Surgery, The First Affiliated Hospital (Hunan Provincial People's Hospital), Hunan Normal University, Changsha, Hunan 410005, People's Republic of China; Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China
| | - Yong Cao
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China
| | - Tianding Wu
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China
| | - Chunyue Duan
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China
| | - Jianhuang Wu
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China
| | - Jianzhong Hu
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China.
| | - Hongbin Lu
- Department of Sport Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China.
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Koyama K, Nakazato K, Maeda S, Kikuchi N, Matsumoto S, Hiranuma K. Association of COL11A1 4603C/T polymorphism with cervical disc degeneration in collegiate wrestlers. J Sports Med Phys Fitness 2017; 58:1695-1700. [PMID: 28944648 DOI: 10.23736/s0022-4707.17.07724-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND The authors previously identified that COL11A1 gene polymorphism is not a susceptibility factor for lumbar disc degeneration (LDD) in athletes. However, the relationship between COL11A1 gene polymorphism and cervical disc degeneration (CDD) remains unclear. We hypothesized that significant associations between COL11A1 4603C/T gene polymorphism and CDD, but not LDD, in collegiate wrestlers exist. This study aims to examine the relationship between CDD, LDD, and COL11A1 4603C/T gene polymorphism in collegiate wrestlers. METHODS The subjects enrolled in this study were 92 (Study-1) and 123 (Study-2) Japanese collegiate male wrestlers. Study-1 and Study-2 were conducted in 2010-2012 and 2012-2015, respectively. RESULTS CDD and LDD prevalence among the wrestlers was 51.1% (47/92) and 43.9% (54/123), respectively. We found that COL11A1 4603C/T was significantly associated with CDD, but not with LDD. Using logistic regression analysis with concomitant confounding factors, we further confirmed that COL11A1 4603C/T was a significant risk factor for CDD (co-dominant genetic model [CC vs. CT+TT]: adjusted odds ratio [OR] 2.28; 95% CI: 1.13-4.59; dominant genetic model [CC+CT vs. TT]: adjusted OR 11.71; 95% CI: 1.36-101.06). CONCLUSIONS Results suggest that COL11A1 4603C/T gene polymorphism is associated with an increased risk of CDD, but not LDD, in Japanese collegiate wrestlers.
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Affiliation(s)
- Koji Koyama
- Department of Judotherapy, Tokyo Ariake University of Medical and Health Science, Tokyo, Japan -
| | - Koichi Nakazato
- Graduate Schools of Health and Sport Science, Nippon Sport Science University, Yokohama, Japan
| | - Shogo Maeda
- Graduate Schools of Health and Sport Science, Nippon Sport Science University, Yokohama, Japan
| | - Naoki Kikuchi
- Graduate Schools of Health and Sport Science, Nippon Sport Science University, Yokohama, Japan
| | - Shingo Matsumoto
- Graduate Schools of Health and Sport Science, Nippon Sport Science University, Yokohama, Japan
| | - Kenji Hiranuma
- Graduate Schools of Health and Sport Science, Nippon Sport Science University, Yokohama, Japan
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Grisdela P, Buser Z, D'Oro A, Paholpak P, Liu JC, Wang JC. Trends analysis of surgical procedures for cervical degenerative disc disease and myelopathy in patients with tobacco use disorder. 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 2017; 26:2386-2392. [PMID: 28488093 DOI: 10.1007/s00586-017-5120-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 04/04/2017] [Accepted: 05/02/2017] [Indexed: 01/13/2023]
Abstract
PURPOSE This study defined the incidence and trends of surgeries performed for patients with cervical disc degeneration with and without tobacco use disorder (TUD). METHODS This study utilized the Humana Inc. database between 2007 and 2013 to identify patients with cervical disc degeneration with or without myelopathy. International Classification of Diseases, ninth revision (ICD-9) and Current Procedural Terminology (CPT) codes determined the initial diagnosis of disc degeneration, myelopathy status and TUD, whether patients received surgery, and TUD status at surgery. RESULTS The prevalence of disc degeneration with myelopathy increased by 32.8% between 2007 and 2013, while disc disease with myelopathy and TUD increased by 91.6%. For patients without myelopathy, the prevalence of disc degeneration alone increased by 65.4%, and disc degeneration with myelopathy increased by 148.7%. Of myelopathy patients, 1717 (6.4%) had TUD and 1024 (59.6%) received surgery, compared to 6508 patients without TUD (26.1%). For patients without myelopathy, 11,337 (3.5%) had TUD and 787 (6.9%) underwent surgery, compared to 9716 patients (3%) without TUD. Of surgical patients, 781 (76.3%) with myelopathy and TUD still had a TUD diagnosis at surgery, and 542 (68.9%) of patients without myelopathy still had a TUD diagnosis at surgery. CONCLUSIONS The prevalence of degenerative disc disease and TUD has increased more than disc disease alone. Patients with TUD were more likely to get surgery, and to have surgeries earlier than patients without TUD. Patients with TUD at the time of the diagnosis of their disc degeneration likely still had a TUD diagnosis at the time of surgery.
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Affiliation(s)
- Phillip Grisdela
- Department of Orthopaedic Surgery, Keck School of Medicine, Elaine Stevely Hoffman Medical Research Center, University of Southern California, 2011 Zonal Ave., HMR 710, Los Angeles, CA, 90033, USA
| | - Zorica Buser
- Department of Orthopaedic Surgery, Keck School of Medicine, Elaine Stevely Hoffman Medical Research Center, University of Southern California, 2011 Zonal Ave., HMR 710, Los Angeles, CA, 90033, USA.
| | - Anthony D'Oro
- Department of Orthopaedic Surgery, Keck School of Medicine, Elaine Stevely Hoffman Medical Research Center, University of Southern California, 2011 Zonal Ave., HMR 710, Los Angeles, CA, 90033, USA
| | - Permsak Paholpak
- Department of Orthopaedic Surgery, Keck School of Medicine, Elaine Stevely Hoffman Medical Research Center, University of Southern California, 2011 Zonal Ave., HMR 710, Los Angeles, CA, 90033, USA
| | - John C Liu
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, USA
| | - Jeffrey C Wang
- Department of Orthopaedic Surgery, Keck School of Medicine, Elaine Stevely Hoffman Medical Research Center, University of Southern California, 2011 Zonal Ave., HMR 710, Los Angeles, CA, 90033, USA
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Incidence and Risk Factors of Postoperative Hematoma Requiring Reoperation in Single-level Lumbar Fusion Surgery. Spine (Phila Pa 1976) 2017; 42:428-436. [PMID: 27390918 DOI: 10.1097/brs.0000000000001768] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Retrospective cohort. OBJECTIVE The purpose of the present study was to examine the incidence and risk factors for postoperative hematoma requiring reoperation in patients undergoing single-level lumbar fusion surgery. SUMMARY OF BACKGROUND DATA Postoperative hematoma can cause devastating neurological consequences after spine surgery. Risk factors for hematoma in specific spine procedures have not been well established. METHODS A cohort of patients undergoing single-level lumbar fusion surgery was constructed from the 2012 to 2013 American College of Surgeons National Surgical Quality Improvement Program dataset using Current Procedural Terminology codes (22533, 22558, 22612, 22630, and 22633). In cases requiring reoperation within 30 days after initial surgery, postoperative hematoma was identified using the ICD-9 code 998.1. Risk factors for postoperative hematoma were assessed with logistic regression modeling. RESULTS Of 5280 patients undergoing single-level lumbar fusion surgery, 27 patients (0.5%) developed a postoperative hematoma requiring reoperation for hematoma evacuation. A heightened incidence of postoperative hematoma was found in patients who were smokers (1.0% vs. 0.4% for nonsmokers, P = 0.016) or who had a diagnosis of bleeding disorder (3.8% vs. 0.5% for those without bleeding disorder, P = 0.007). Multivariate logistic regression analysis indicated that the adjusted odds ratios for postoperative hematoma associated with smoking and bleeding disorder were 3.34 (95% confidence interval, 1.15-9.71) and 10.2 (95% confidence interval, 1.9-54.8), respectively. CONCLUSION Smoking and bleeding disorder appear to be major risk factors for postoperative hematoma requiring reoperation after single-level lumbar fusion surgery. Intervention programs targeting patients with these risk factors are needed to reduce their excess risk of postoperative hematoma. LEVEL OF EVIDENCE 3.
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Walker CT, Bonney PA, Martirosyan NL, Theodore N. Genetics Underlying an Individualized Approach to Adult Spinal Disorders. Front Surg 2016; 3:61. [PMID: 27921035 PMCID: PMC5118450 DOI: 10.3389/fsurg.2016.00061] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 10/26/2016] [Indexed: 12/22/2022] Open
Abstract
Adult spinal disorders are a significant cause of morbidity across the world and carry significant health and economic burdens. Genetic predispositions are increasingly considered for these conditions and are becoming understood. Advances in molecular technologies since the mid-1990s have made possible genetic characterizations of these diseases in many populations, and recent findings have provided insight into the underlying pathophysiologic mechanisms. These studies have made clear the genetic heterogeneity producing clinical phenotypes and suggest that individualized treatments are possible in the future. We review the genetics and heritability of cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament and perform a systematic review of the genetics of adult lumbar degenerative scoliotic deformity, highlighting recent discoveries and the potential for personalized future therapeutics for these patients.
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Affiliation(s)
- Corey T Walker
- Department of Neurosurgery, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute , Phoenix, AZ , USA
| | - Phillip A Bonney
- Department of Neurosurgery, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute , Phoenix, AZ , USA
| | - Nikolay L Martirosyan
- Department of Neurosurgery, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute , Phoenix, AZ , USA
| | - Nicholas Theodore
- Department of Neurosurgery, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute , Phoenix, AZ , USA
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Does Tobacco Use Attenuate Benefits of Early Decompression in Patients With Cervical Myelopathy? Spine (Phila Pa 1976) 2016; 41:1565-1569. [PMID: 27043195 DOI: 10.1097/brs.0000000000001597] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN A retrospective cohort. OBJECTIVE This study investigates the interplay between duration of preoperative symptoms and smoking status with respect to postoperative outcomes in patients with cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA Many studies have established the harms of smoking and several have identified the benefits of early decompression in patients with cervical myelopathy, but to our knowledge, none have assessed the relationship between these two variables. METHODS The medical records of all 212 patients operated on by the senior author between March 2005 and July 2012 were reviewed. Inclusion criteria were the diagnosis of CSM with a Nurick score, surgical intervention, and at least 2 years of follow-up. Patients were categorized according to smoking status and quantification of tobacco use by packs per day and pack-years, and duration of symptoms according to thresholds of 6, 12, or 24 months. Age, sex, preoperative Nurick score, duration of preoperative symptoms, duration of follow-up, procedure performed, prior surgery, number of levels operated on, diabetes status, ethanol use, and signal change on preoperative magnetic resonance imaging were also recorded for ordered logistical regression analysis. RESULTS One hundred twenty-five patients met all criteria. Eighty patients were smokers and 45 were nonsmokers. The median change in Nurick score for nonsmokers was 2 compared with 1 in smokers. Nonsmokers had a statistically significant likelihood of decreased change in Nurick score for symptom duration of greater than 24 months (odds ratio = 0.06, P = 0.0025). Smokers did not show a significant difference in the change in Nurick score for any threshold of symptom duration. CONCLUSION Increased duration of symptoms significantly affects outcomes in surgical decompression of CSM. A history of cigarette use may attenuate the benefit of early decompression and results in lower improvement in Nurick score regardless of symptom duration. LEVEL OF EVIDENCE 3.
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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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Abode-Iyamah KO, Stoner KE, Grossbach AJ, Viljoen SV, McHenry CL, Petrie MA, Dahdaleh NS, Grosland NM, Shields RK, Howard MA. Effects of brain derived neurotrophic factor Val66Met polymorphism in patients with cervical spondylotic myelopathy. J Clin Neurosci 2015; 24:117-21. [PMID: 26461908 DOI: 10.1016/j.jocn.2015.07.016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 07/18/2015] [Indexed: 11/29/2022]
Abstract
Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord related disability in the elderly. It results from degenerative narrowing of the spinal canal, which causes spinal cord compression. This leads to gait instability, loss of dexterity, weakness, numbness and urinary dysfunction. There has been indirect data that implicates a genetic component to CSM. Such a finding may contribute to the variety in presentation and outcome in this patient population. The Val66Met polymorphism, a mutation in the brain derived neurotrophic factor (BDNF) gene, has been implicated in a number of brain and psychological conditions, and here we investigate its role in CSM. Ten subjects diagnosed with CSM were enrolled in this prospective study. Baseline clinical evaluation using the modified Japanese Orthopaedic Association (mJOA) scale, Nurick and 36-Item Short Form Health Survey (SF-36) were collected. Each subject underwent objective testing with gait kinematics, as well as hand functioning using the Purdue Peg Board. Blood samples were analyzed for the BDNF Val66Met mutation. The prevalence of the Val66Met mutation in this study was 60% amongst CSM patients compared to 32% in the general population. Individuals with abnormal Met allele had worse baseline mJOA and Nurick scores. Moreover, baseline gait kinematics and hand functioning testing were worse compared to their wild type counterpart. BDNF Val66Met mutation has a higher prevalence in CSM compared to the general population. Those with BDNF mutation have a worse clinical presentation compared to the wild type counterpart. These findings suggest implication of the BDNF mutation in the development and severity of CSM.
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Affiliation(s)
- Kingsley O Abode-Iyamah
- Department of Neurosurgery, Carver College of Medicine, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52245, USA.
| | - Kirsten E Stoner
- Department of Bioengineering, The University of Iowa, Iowa City, IA, USA
| | - Andrew J Grossbach
- Department of Neurosurgery, Carver College of Medicine, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52245, USA
| | - Stephanus V Viljoen
- Department of Neurosurgery, Carver College of Medicine, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52245, USA
| | - Colleen L McHenry
- Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
| | - Michael A Petrie
- Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
| | - Nader S Dahdaleh
- Department of Neurosurgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Nicole M Grosland
- Department of Bioengineering, The University of Iowa, Iowa City, IA, USA
| | - Richard K Shields
- Department of Bioengineering, The University of Iowa, Iowa City, IA, USA; Department of Veterans Affairs, VA Medical Center, Iowa City, IA, USA
| | - Matthew A Howard
- Department of Neurosurgery, Carver College of Medicine, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52245, USA
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Abstract
STUDY DESIGN Retrospective cohort. OBJECTIVE The purpose of this study was to compare outcomes of surgical treatment of cervical myelopathy between smokers and nonsmokers as assessed by the Nurick score. SUMMARY OF BACKGROUND DATA The harmful effects of smoking on healing have been well established. However, the effect of smoking on postoperative outcomes for cervical myelopathy has not been specifically evaluated. METHODS The medical records of 212 patients who underwent surgery for cervical spondylotic myelopathy were reviewed. Inclusion criteria were the diagnosis of cervical spondylotic myelopathy with a Nurick score, surgical intervention, and at least 2 years of follow-up. The patients were categorized into 2 groups according to smoking status and stratified according to pack years and packs per day. Age at presentation, sex, preoperative and postoperative Nurick score, duration of symptoms preoperatively, duration of follow-up, procedure performed, surgical approach, number of levels fused, diabetes status, cocaine use, ethanol use, preoperative magnetic resonance imaging signal change, and whether the patient belonged to the Veterans Administration (VA) were recorded. Analysis was done using simple linear regression and multiple regression. RESULTS Univariate analysis demonstrated a postoperative improvement in nonsmokers of 1.53 points on the Nurick scale compared with 0.6 points in smokers (P < 0.001). There is a progressive decrease in improvement as the number of pack years and packs per day increase (P < 0.001). There is a greater improvement in Nurick score with greater (worse) preoperative score but only in patients with fewer than 25 pack years. Smoking status is not associated with preoperative Nurick score. CONCLUSION Smoking status is associated with poor improvement in Nurick score after surgical treatment of cervical myelopathy. Smoking may have a directly toxic effect on the intrinsic healing capability of the spinal cord, particularly beyond 25 pack years. LEVEL OF EVIDENCE 3.
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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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Genetics and heritability of cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament: results of a systematic review. Spine (Phila Pa 1976) 2013; 38:S123-46. [PMID: 23963008 DOI: 10.1097/brs.0b013e3182a7f478] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Systematic review. OBJECTIVE To answer the following 3 clinical questions: (1) What is the evidence supporting a heritable predisposition for cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL)? (2) What specific genetic polymorphisms have been associated with CSM and OPLL? (3) What is the evidence supporting a genetic basis for predicting postoperative outcomes for patients with CSM and OPLL? SUMMARY OF BACKGROUND DATA OPLL and CSM are thought to be multifactorial conditions resulting from a combination of environmental and genetic factors. METHODS A systematic review of the English language literature was undertaken for articles published between 1980 and November 7, 2012. The strength of evidence was determined by 2 independent reviewers using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria for studies addressing the first question of heritability and using the criteria set forth by the HuGENet Working Group in the Venice Interim Guidelines to address the last 2 questions of genetic association. RESULTS Of the 118 citations identified through the initial literature search, a total of 23 articles remained after application of inclusion/exclusion criteria. The 3 family association studies related to question 1 supported the principle of an inherited predisposition to CSM and OPLL; however, the strength of evidence supporting these findings was low. Within the 19 case-control studies related to question 2, 2 single nucleotide polymorphisms (COL6A1/Intron 32(-29) and COL11A2/Intron 6(-4)) were observed at higher frequencies in OPLL cases than in controls in more than 1 study and may be associated with its development. There was insufficient evidence to support an association between CSM and any specific single nucleotide polymorphism or haplotype or to support the association of specific gene alleles with postoperative CSM outcomes. CONCLUSION Existing family studies provide support for the principle of an inherited predisposition to CSM and OPLL. Multiple studies support the association of 2 collagen gene related single nucleotide polymorphisms with OPLL; however, there is insufficient evidence to support the association between CSM and any genetic polymorphism or to support a genetic predictor of surgical outcome. SUMMARY STATEMENTS: STATEMENT 1: Existing family studies provide support for the principle of an inherited predisposition to CSM and OPLL. STATEMENT 2: Two SNPs related to the collagen 6A1 gene (COL6A1/Intron 32(-29)) and the collagen 11A2 gene (COL11A2/Intron 6(-4)) have been associated with OPLL in multiple studies and may be associated with its development. STATEMENT 3: No statement can be made from the literature regarding the association of specific SNPs or haplotypes with CSM. STATEMENT 4: No statement can be made from the literature regarding genetic predictors of surgical outcome in the context of OPLL or CSM.
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Matsunaga S, Komiya S, Toyama Y. Risk factors for development of myelopathy in patients with cervical spondylotic cord compression. 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 2013; 24 Suppl 2:142-9. [PMID: 23700231 DOI: 10.1007/s00586-013-2839-9] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Revised: 02/01/2013] [Accepted: 05/12/2013] [Indexed: 10/26/2022]
Abstract
PURPOSE To clarify risk factors for the development of myelopathy in patients with cervical spondylotic cord compression. METHOD The authors reviewed articles in which risk factors for the development of myelopathy in patients with cervical spondylotic cord compression were discussed. Ossification of the posterior longitudinal ligament (OPLL) was also reviewed as a disease which causes cervical cord compression to clarify pathomechanism of the development of myelopathy. RESULTS Cervical motion segment disorders are considered to be multifactorial, and developmental size of the canal and foramina, pathological encroachment, biomechanical effects, and circulatory deficiencies are always present to some degree. Static and dynamic factors should be considered for the development of myelopathy. To clarify the pathomechanism of the development of myelopathy in patients with cervical spondylotic spinal cord compression, the exact natural history of CSM should be understood. CONCLUSION Several predictable risk factors for the development of myelopathy have been proposed in CSM or OPLL studies, but they were not definitive. Further prospective population-based study is needed to clarify the mechanism.
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Affiliation(s)
- Shunji Matsunaga
- Department of Orthopaedic Surgery, Imakiire General Hospital, 4-16 Shimotatsuo chou, Kagoshima, 892-8502, Japan,
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