Development and validation of a MEDLINE search filter/hedge for degenerative cervical myelopathy

Abstract Background Degenerative cervical myelopathy (DCM) is a common condition with many unmet clinical needs. Pooled analysis of studies is an important tool for advancing medical understanding. This process starts with a systematic search of the literature. Identification of studies in DCM is challenged by a number of factors, including non-specific terminology and index terms. Search filters or HEDGEs, are search strings developed and validated to optimise medical literature searches. We aimed to develop a search filter for DCM for the MEDLINE database. Methods The diagnostic test assessment framework of a “development dataset” and seperate “validation dataset” was used. The development dataset was formed by hand searching four leading spinal journals (Spine, Journal of Neurosurgery Spine, Spinal Cord and Journal of Spinal Disorders and Techniques) in 2005 and 2010. The search filter was initially developed focusing on sensitivity and subsequently refined using NOT functions to improve specificity. One validation dataset was formed from DCM narrative and systematic review articles and the second, articles published in April of 1989, 1993, 1997, 2001, 2005, 2009, 2013 and 2017 retrieved via the search MeSH term ‘Spine’. Metrics of sensitivity, specificity, precision and accuracy were used to test performance. Results Hand searching identified 77/1094 relevant articles for 2005 and 55/1199 for 2010. We developed a search hedge with 100% sensitivity and a precision of 30 and 29% for the 2005 and 2010 development datasets respectively. For the selected time periods, EXP Spine returned 2113 publications and 30 were considered relevant. The search filter identified all 30 relevant articles, with a specificity of 94% and precision of 20%. Of the 255 references listed in the narrative index reviews, 225 were indexed in MEDLINE and 165 (73%) were relevant articles. All relevant articles were identified and accuracy ranged from 67 to 97% over the three reviews. Of the 42 articles returned from 3 recent systematic reviews, all were identified by the filter. Conclusions We have developed a highly sensitive hedge for the research of DCM. Whilst precision is similarly low as other hedges, this search filter can be used as an adjunct for DCM search strategies

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

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

Recovery priorities in degenerative cervical myelopathy: a cross-sectional survey of an international, online community of patients.

OBJECTIVES: To establish the recovery priorities of individuals suffering with degenerative cervical myelopathy (DCM). DESIGN: A cross-sectional, observational study. SETTING: Patients from across the world with a diagnosis of DCM accessed the survey over an 18-month period on Myelopathy.org, an international myelopathy charity. PARTICIPANTS: 481 individuals suffering from DCM completed the online survey fully. MAIN OUTCOME MEASURES: Functional recovery domains were established through qualitative interviews and a consensus process. Individuals were asked about their disease characteristics, including limb pain (Visual Analogue Scale) and functional disability (patient-derived version of the modified Japanese Orthopaedic Association score). Individuals ranked recovery domains (arm and hand function, walking, upper body/trunk function, sexual function, elimination of pain, sensation and bladder/bowel function) in order of priority. Priorities were analysed as the modal first priority and mean ranking. The influence of demographics on selection was analysed, with significance p<0.05. RESULTS: Of 659 survey responses obtained, 481 were complete. Overall, pain was the most popular recovery priority (39.9%) of respondents, followed by walking (20.2%), sensation (11.9%) and arm and hand function (11.5%). Sexual function (5.7%), bladder and bowel (3.7%) and trunk function (3.5%) were chosen less frequently. When considering the average ranking of symptoms, while pain remained the priority (2.6±2.0), this was closely followed by walking (2.9±1.7) and arm/hand function (3.0±1.4). Sensation ranked lower (4.3±2.1). With respect to disease characteristics, overall pain remained the recovery priority, with the exception of patients with greater walking impairment (p<0.005) who prioritised walking, even among patients with lower pain scores. CONCLUSIONS: This is the first study investigating patient priorities in DCM. The patient priorities reported provide an important framework for future research and will help to ensure that it is aligned with patient needs.NIHR Welcome Trus

Cord compression defined by MRI is the driving factor behind the decision to operate in Degenerative Cervical Myelopathy despite poor correlation with disease severity.

OBJECTIVES:The mainstay treatment for Degenerative Cervical Myelopathy (DCM) is surgical decompression. Not all cases, however, are suitable for surgery. Recent international guidelines advise surgery for moderate to severe disease as well as progressive mild disease. The goal of this study was to examine the factors in current practice that drive the decision to operate in DCM. STUDY DESIGN:Retrospective cohort study. METHODS:1 year of cervical spine MRI scans (N = 1123) were reviewed to identify patients with DCM with sufficient clinical documentation (N = 39). Variables at surgical assessment were recorded: age, sex, clinical signs and symptoms of DCM, disease severity, and quantitative MRI measures of cord compression. Bivariate correlations were used to compare each variable with the decision to offer the patient an operation. Subsequent multivariable analysis incorporated all significant bivariate correlations. RESULTS:Of the 39 patients identified, 25 (64%) were offered an operation. The decision to operate was significantly associated with narrower non-pathological canal and cord diameters as well as cord compression ratio, explaining 50% of the variance. In a multivariable model, only cord compression ratio was significant (p = 0.017). Examination findings, symptoms, functional disability, disease severity, disease progression, and demographic factors were all non-significant. CONCLUSIONS:Cord compression emerged as the main factor in surgical decision-making prior to the publication of recent guidelines. Newly identified predictors of post-operative outcome were not significantly associated with decision to operate

Developing Peri-Operative Rehabilitation in Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 6]: An Unexplored Opportunity?

Study Design Narrative review. Objective Degenerative cervical myelopathy is one of the most frequent impairments of the spinal cord encountered internationally in adults. Currently, surgical decompression is the recommended treatment for people with DCM (PwCM) presenting with moderate to severe symptoms or neurological deficits. However, despite surgical intervention, not all patients make a complete recovery due to the irreversible tissue damage within the spinal cord. The objective of this review is to describe the state and gaps in the current literature on rehabilitation for PwCM and possible innovative rehabilitation strategies. Methods Literature search. Results In other neurological disorders such as stroke and acute traumatic spinal cord injury (SCI), timely and strategic rehabilitation has been shown to be indispensable for maximizing functional outcomes, and it is imperative that appropriate perioperative rehabilitative interventions accompany surgical approaches in order to enable the best outcomes. In this review, the current state of knowledge regarding rehabilitation for PwCM is described. Additionally, various therapies that have shown to improve outcomes in comparable neurological conditions such as stroke and SCI which may be translated to DCM will be reviewed. Conclusions We conclude that locomotor training and arm/hand therapy may benefit PwCM. Further, we conclude that body weight support, robotic assistance, and virtual/augmented reality therapies may be beneficial therapeutic analogs to locomotor and hand therapies

Academic neurosurgery in the UK: present and future directions.

Academic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training. Life as an academic consultant is also described. Funding is explored, for the specialty as a whole and at the individual level. UK academic neurosurgical organisations are highlighted. Finally, the UK's international standing is considered

Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling

Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines of evidence point to factors present following demyelination that specifically inhibit differentiation of cells capable of generating remyelinating oligodendrocytes. We have previously demonstrated that myelin debris generated by demyelination inhibits remyelination by inhibiting OPC differentiation and that the inhibitory effects are associated with myelin proteins. In the present study, we narrow down the spectrum of potential protein candidates by proteomic analysis of inhibitory protein fractions prepared by CM and HighQ column chromatography followed by BN/SDS/SDS–PAGE gel separation using Nano-HPLC-ESI-Q-TOF mass spectrometry. We show that the inhibitory effects on OPC differentiation mediated by myelin are regulated by Fyn-RhoA-ROCK signalling as well as by modulation of protein kinase C (PKC) signalling. We demonstrate that pharmacological or siRNA-mediated inhibition of RhoA-ROCK-II and/or PKC signalling can induce OPC differentiation in the presence of myelin. Our results, which provide a mechanistic link between myelin, a mediator of OPC differentiation inhibition associated with demyelinating pathologies and specific signalling pathways amenable to pharmacological manipulation, are therefore of significant potential value for future strategies aimed at enhancing CNS remyelination

Targeting patient recovery priorities in degenerative cervical myelopathy:design and rationale for the RECEDE-Myelopathy trial-study protocol

Introduction: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. Methods and analysis: RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. Study design: Clinical trial protocol V.2.2 October 2020. Ethics and dissemination: Ethical approval has been obtained from HRA - Wales. The results will be presented at an international and national scientific conferences and in a peer-reviewed journals.Trial registration number: ISRCTN Number: ISRCTN16682024.</p