"I am not delusional!" Sensory dysaesthesia secondary to degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction, most classically presenting with a broad-based gait and clumsy hands. Limb sensory loss and paraesthesia are considered common symptoms of DCM. However, we report an unusual case of a patient presenting with prominent and atypical sensory symptoms. The patient repeatedly presented to accident and emergency complaining of her body resembling a wet gel-like substance that she attributed to the use of olive oil moisturising cream. The patient was found to have myelopathic signs on examination and MRI consistent with severe cervical myelopathy. She subsequently underwent successful decompressive anterior cervical discectomy, as recommended by international guidelines. This case serves to remind health professionals of uncommon presentations of common disease and the importance of maintaining a wide initial differential diagnosis

Route to diagnosis of degenerative cervical myelopathy in a UK healthcare system: a retrospective cohort study.

OBJECTIVES: Degenerative cervical myelopathy (DCM) presents insidiously, making initial diagnosis challenging. Surgery has been shown to prevent further disability but existing spinal cord damage may be permanent. Delays in surgery lead to increased disability and reduced postoperative improvements. Therefore, rapid surgical assessment is key to improving patient outcomes. Unfortunately, diagnosis of DCM in primary care is often delayed. This study aimed to characterise patients with DCM route to diagnosis and surgical assessment as well as to plot disease progression over time. DESIGN: Retrospective, observational cohort study. SETTING: Single, tertiary centre using additional clinical records from primary and secondary care centres. PARTICIPANTS: One year of cervical MRI scans conducted at a tertiary neurosciences centre (n=1123) were screened for cervical cord compression, a corresponding clinical diagnosis of myelopathy and sufficient clinical documentation to plot a route to diagnosis (n=43). PRIMARY OUTCOME MEASURES: Time to diagnosis from symptom onset, route to diagnosis and disease progression were the primary outcome measures in this study. Disease severity was approximated using a prospectively validated method for inferring modified Japanese Orthopaedic Association (i-mJOA) functional scoring from clinical documentation. RESULTS: Patients received a referral to secondary care 6.4±7.7 months after symptom onset. Cervical MRI scanning and neurosurgical review occurred 12.5±13.0 and 15.8±13.5 months after symptom onset, respectively. i-mJOA was 16.0±1.7 at primary care assessment and 14.8±2.5 at surgical assessment. 61.0% of patients were offered operations. For those who received surgery, time between onset and surgery was 22.1±13.2 months. CONCLUSIONS: Route to surgical assessment was heterogeneous and lengthy. Some patients deteriorated during this period. This study highlights the need for a streamlined pathway by which patients with cervical cord compression can receive timely assessment and treatment by a specialist. This would improve outcomes for patients using existing treatments.Research in the senior author’s laboratory is supported by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. MRNK is supported by a NIHR Clinician Scientist Award. Disclaimer: This report is independent research arising from a Clinician Scientist Award, CS-2015-15-023, supported by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health

Quantitative analysis of medical students’ and physicians’ knowledge of degenerative cervical myelopathy

Objectives: We have previously identified a delay in general practitioner (GP) referrals for patients with degenerative cervical myelopathy (DCM). The aim of this study was to evaluate whether an education gap existed for DCM along the GP training pathway by quantitatively assessing training in, and knowledge of, this condition. Design: Gap analysis: comparison of DCM to other conditions. Comparators selected on the basis of similar presentation/epidemiology (multiple sclerosis), an important spinal emergency (cauda equina syndrome) and a common disease (diabetes mellitus). Subjects: Medical students, foundation doctors and GP trainees. Primary and secondary outcome measures: (1) Assessment of training: quantitative comparison of references to DCM in curricula (undergraduate/postgraduate) and commonly used textbooks (Oxford Handbook Series), to other conditions using modal ranks. (2) Assessment of knowledge: using standardised questions placed in an online question-bank (Passmedicine). Results were presented relative to the question-bank mean (+/−). Results: DCM had the lowest modal rank of references to the condition in curricula analysis and second lowest modal rank in textbook analysis. In knowledge analysis questions were attempted 127 457 times. Performance for DCM questions in themes of presentation (+6.1%), workup (+0.1%) and management (+1.8%) were all greater than the question-bank mean and within one SD. For students and junior trainees, there was a serial decrease in performance from presentation and workup (−0.7% to +10.4% relative to question-bank mean) and management (−0.6% to −3.9% relative to question-bank mean). Conclusions: Although infrequently cited in curricula and learning resources, knowledge relating to DCM was above average. However, knowledge relating to its management was relatively poor

Degenerative Cervical Myelopathy and the Aging Spine: Introduction to the Special Issue.

Degenerative Cervical Myelopathy (DCM) is the most common cause of spinal cord injury in the world, but despite this, there remains many areas of uncertainty regarding the management of the condition. This special issue was dedicated to presenting current research topics in DCM. Within this issue, 12 publications are presented, including an introductory narrative overview of DCM and 11 articles comprising 9 research papers and 2 systematic reviews focusing on different aspects, ranging from genetic factors to clinical assessments, imaging, sagittal balance, surgical treatment, and outcome prediction. These articles represented contributions from a diverse group of researchers coming from multiple countries, including Switzerland, Germany, Italy, United Kingdom, United States, South Korea, and Canada

Degenerative Cervical Myelopathy: A Brief Review of Past Perspectives, Present Developments, and Future Directions.

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord injury in developed countries; its prevalence is increasing due to the ageing of the population. DCM causes neurological dysfunction and is a significant cause of disability in the elderly. It has important negative impacts on the quality of life of those affected, as well as on their caregivers. DCM is triggered by a variety of degenerative changes in the neck, which affect one or more anatomical structures, including intervertebral discs, vertebrae, and spinal canal ligaments. These changes can also lead to structural abnormalities, leading to alterations in alignment, mobility, and stability. The principle unifying problem in this disease, regardless of the types of changes present, is injury to the spinal cord due to compression by static and/or dynamic forces. This review is partitioned into three segments that focus on key elements of the past, the present, and the future in the field, which serve to introduce the focus issue on "Degenerative Cervical Myelopathy and the Aging Spine". Emerging from this review is that tremendous progress has been made in the field, particularly in recent years, and that there are exciting possibilities for further advancements of patient care

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

Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells

Although oligodendrocytes constitute a significant proportion of cells in the central nervous system (CNS), little is known about their intermediary metabolism. We have therefore characterised metabolic functions of primary oligodendrocyte precursor cell cultures at late stages of differentiation using isotope-labelled metabolites. We report that differentiated oligodendrocyte lineage cells avidly metabolise glucose in the cytosol and pyruvate derived from glucose in the mitochondria. The labelling patterns of metabolites obtained after incubation with [1,2-13C]glucose demonstrated that the pentose phosphate pathway (PPP) is highly active in oligodendrocytes (approximately 10% of glucose is metabolised via the PPP as indicated by labelling patterns in phosphoenolpyruvate). Mass spectrometry and magnetic resonance spectroscopy analyses of metabolites after incubation of cells with [1-13C]lactate or [1,2-13C]glucose, respectively, demonstrated that anaplerotic pyruvate carboxylation, which was thought to be exclusive to astrocytes, is also active in oligodendrocytes. Using [1,2-13C]acetate we show that oligodendrocytes convert acetate into acetyl-CoA which is metabolized in the tricarboxylic acid cycle. Analysis of labelling patterns of alanine after incubation of cells with [1,2-13C]acetate and [1,2-13C]glucose showed catabolic oxidation of malate or oxaloacetate. In conclusion, we report that oligodendrocyte lineage cells at late differentiation stages are metabolically highly active cells that are likely to contribute considerably to the metabolic activity of the CNS.Grant sponsor: The UK Multiple Sclerosis Society and Qatar Foundation. The work was further supported by core funding from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/glia.2290

The pathophysiology of degenerative cervical myelopathy and the physiology of recovery following decompression

Background: Degenerative cervical myelopathy (DCM), also known as cervical spondylotic myelopathy is the leading cause of spinal cord compression in adults. The mainstay of treatment is surgical decompression, which leads to partial recovery of symptoms, however, long term prognosis of the condition remains poor. Despite advances in treatment methods, the underlying pathobiology is not well-known. A better understanding of the disease is therefore required for the development of treatments to improve outcomes following surgery. Objective: To systematically evaluate the pathophysiology of DCM and the mechanism underlying recovery following decompression. Methods: A total of 13,808 published articles were identified in our systematic search of electronic databases (PUBMED, WEB OF SCIENCE). A total of 51 studies investigating the secondary injury mechanisms of DCM or physiology of recovery in animal models of disease underwent comprehensive review. Results: Forty-seven studies addressed the pathophysiology of DCM. Majority of the studies demonstrated evidence of neuronal loss following spinal cord compression. A number of studies provided further details of structural changes in neurons such as myelin damage and axon degeneration. The mechanisms of injury to cells included direct apoptosis and increased inflammation. Only four papers investigated the pathobiological changes that occur in spinal cords following decompression. One study demonstrated evidence of axonal plasticity following decompressive surgery. Another study demonstrated ischaemic-reperfusion injury following decompression, however this phenomenon was worse when decompression was delayed. Conclusions: In preclinical studies, the pathophysiology of DCM has been poorly studied and a number of questions remain unanswered. The physiological changes seen in the decompressed spinal cord has not been widely investigated and it is paramount that researchers investigate the decompressed spinal cord further to enable the development of therapeutic tools, to enhance recovery following surgery

Research Inefficiency in Degenerative Cervical Myelopathy: Findings of a Systematic Review on Research Activity Over the Past 20 Years.

STUDY DESIGN: Scoping review. OBJECTIVE: To describe activity, themes and trends in degenerative cervical myelopathy (DCM) research over the past 20 years with a view to considering DCM research inefficiency. METHODS: A systematic review of MEDLINE and Embase for "Cervical" AND "Myelopathy" was conducted following PRISMA guidelines. Full-text papers in English, exclusively studying DCM, published between January 1, 1995 and December 31, 2015 were considered eligible. Country of origin, number of papers published, number of patients studied, research theme, and year of publication were assessed. Comparison was made between developed and developing countries. RESULTS: A total of 1485 papers and 4 117 051 patients were included. Japan published more papers (450) than any other country while the United States studied the greatest number of patients (3 674 737). Over 99.4% of papers and 78.6% of patients were from developed countries. The number of papers (r = 0.96, P < .001) and patients (r = 0.83 P < .001) studied each year increased significantly overall and for both developed (r = 0.93, P < .001; r = 0.81, P < .001) and developing countries (r = 0.90, P < .001; r = 0.87, P < .001). Surgery was the most prevalent theme (58.3% papers; 55.7% patients) for developed and developing countries. Research from developing countries showed greater thematic variability. CONCLUSIONS: DCM research activity is increasing internationally, with surgery remaining the focus. Research output has predominantly been from developed countries; however, the rate of growth for developed and developing countries is comparable

Mathematical Modeling of Neuronal Logic, Memory and Clocking Circuits

The differential equations used to model biological neurons and the chemical kinetics involved in synaptic excitation and inhibition have been well-established for a number of decades. For the first time, this paper presents mathematical and computational models of a neuronal binary oscillator half-adder, a neuronal Set-Reset (SR) flip-flop and a simple neuronal clocking circuit, which have all been shown to be noise resistant. In modern computers, the half-adder is the basic component to perform logic, the SR flip-flop is used to store memory and clocking circuits are used to synchronize components in parts of the computer. These novel circuits will provide the world with neuronal assays that can measure the functionality of the neurons and hence provide more information than is available with current technology. The authors are not proposing to build conventional computers with these components (they would be too slow to be practical) but the simple circuits could be used to measure the functionality of diseased circuits which are subjected to certain drugs. Neurological conditions research into Alzheimer’s disease, epilepsy and Parkinson’s disease, for example, would all benefit from this research. These assays for neuronal degradation could have major implications for the National Center for the Replacement, Refinement and Reduction of Animals in Research — otherwise known as the NC3R agenda