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Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies.

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.

SUBMITTER: Pope DH

PROVIDER: S-EPMC7019856 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies.

Pope Daniel H DH Davies Benjamin M BM Mowforth Oliver D OD Bowden A Ramsay AR Kotter Mark R N MRN

Journal of clinical medicine 20200120 1

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 ...[more]

PMID: 31968564

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Project description:IntroductionDegenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord impairment worldwide, encompassing chronic compression of the spinal cord, neurological disability and diminished quality of life. Evidence on the contribution of environmental factors is sparse; in particular, the role of nutrition in DCM is unknown. The objective of this review was to assess the effect of nutrition on DCM susceptibility, severity and surgical outcome.MethodsA systematic review in MEDLINE and Embase was conducted following PRISMA guidelines. Full-text papers in English papers, focussing on cervical myelopathy and nutrition, published before January 2020 were considered eligible. Quality assessments were performed using the GRADE assessment tool. Patient demographics, nutritional factor and DCM outcomes measures were recorded. Relationships between nutritional factors, interventions and disease prognosis were assessed.ResultsIn total, 5835 papers were identified of which 44 were included in the final analysis. DCM patients with pathological weight pre-operatively were more likely to see poorer improvements post-surgically. These patients experienced poorer physical and mental health improvements from surgery compared to normal weight patients and were more likely to suffer from post-operative complications such as infection, DVT, PE and hospital readmissions. Two trials reporting benefits of nutritional supplements were identified, with 1 suggesting Cerebrolysin to be significant in functional improvement. An unbalanced diet, history of alcohol abuse and malnourishment were associated with poorer post-operative outcome.ConclusionAlthough the overall strength of recommendation is low, current evidence suggests nutrition may have a significant role in optimising surgical outcome in DCM patients. Although it may have a role in onset and severity of DCM, this is a preliminary suggestion. Further work needs to be done on how nutrition is defined and measured, however, the beneficial results from studies with nutritional interventions suggest nutrition could be a treatment target in DCM.

Project description:BackgroundDegenerative Cervical Myelopathy (DCM) is one of the most common degenerative disorders of cervical spine and sources of cord dysfunction in adults. It usually manifests with neurologic presentations such as loss of dexterity and gait issues. Treatment for moderate and severe cases of DCM is surgical decompression of the region. There are many approaches available for surgical intervention which could be categorized into anterior and posterior based on the side of neck where operation takes place. Additionally, for certain cases the hybridized anterior-posterior combined surgery is indicated. While there are many technical differences between these approaches with each having its own advantages, the complications and safety profiles of them are not fully disclosed. This protocol aims to systematically search for current reports on complications of surgical decompression methods of DCM and pool them for robust evidence generation.MethodSearch will be carried out in PubMed, Scopus, and Cochrane databases for retrospective and prospective surgical series, cohorts, or trials being performed for DCM with at least a sample size of 20 patients. Query strings will be designed to capture reports with details of complications with no year limit. Studies not being original (e.g., review articles, case reports, etc.), not in English, having patients younger than 18-years-old, and not reporting at least one complication will be excluded. Two independent reviewers will review the titles and abstracts for first round of screening. Full text of retrieved studies from previous round will be screened again by the same reviewers. In case of discrepancy, the third senior reviewer will be consulted. Eligible studies will then be examined for data extraction where data will be recorded into standardized form. Cumulative incidence and 95% confidence intervals of complication will be then pooled based on generalized linear mixed models with consideration of approach of surgery as subgroups. Heterogeneity tests will be performed for assessment of risk of bias.DiscussionThis systematic review is aimed at providing practical information for spine surgeons on the rates of complications of different surgical approaches of DCM decompression. Proper decision-making regarding the surgical approach in addition to informing patients could be facilitated through results of this investigation.

Project description:Degenerative cervical myelopathy (DCM) is a prevalent condition in which spinal degeneration causes cord compression and neurological dysfunction. The spinal cord is anatomically complex and operates in conjunction with the brain, the musculoskeletal system, and numerous organs to control numerous functions, including simple and coordinated movement, sensation, and autonomic functions. As a result, accurate and comprehensive measurement of spinal cord function in patients with DCM and other spinal pathologies is challenging. This project aimed to summarize the neurological, functional, and quality of life (QoL) outcome measures currently in use to quantify impairment in DCM. A systematic review of the literature was performed to identify prospective studies with at least 100 DCM subjects that utilized one or more quantitative neurological, functional, or QoL outcome measures. A total of 148 studies were identified. The most commonly used instruments were subjective functional scales including the Japanese Orthopedic Association (JOA) (71 studies), modified JOA (mJOA) (66 studies), Neck Disability Index (NDI) (54 studies), and Nurick (39 studies), in addition to the QoL measure Short-Form-36 (SF-36, 52 studies). A total of 92% (320/349) of all outcome measures were questionnaires, whereas objective physical testing of neurological function (strength, gait, balance, dexterity, or sensation) made up 8% (29/349). Studies utilized an average of 2.36 outcomes measures, while 58 studies (39%) utilized only a single outcome measure. No studies were identified that specifically assessed the dorsal column sensory pathway or respiratory, bowel, or sexual function. In the past five years, there were no significant differences in the number of total, functional, or QoL outcome measures used, but physical testing of neurological function has increased (p = 0.005). Prior to 2017, cervical spondylotic myelopathy (CSM) was the most frequently used term to describe the study population, whereas in the last five years, DCM has become the preferred terminology. In conclusion, clinical studies of DCM typically utilize limited data to characterize impairment, often relying on subjective, simplistic, and non-specific measures that do not reflect the complexity of the spinal cord. Although accurate measurement of impairment in DCM is challenging, it is necessary for early diagnosis, monitoring for deterioration, and quantifying recovery after therapeutic interventions. Clinical decision-making and future clinical studies in DCM should employ a combination of subjective and objective assessments to capture the multitude of spinal cord functions to improve clinical management and inform practice guidelines.

Project description:BackgroundDegenerative 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.ObjectiveThis 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.MethodsTo 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.ResultsThe 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.ConclusionsDCM 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.

Dataset Information

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies.

Publications

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies.

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