Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms.
Ontology highlight
ABSTRACT:
SUBMITTER: Tu J
PROVIDER: S-EPMC8001572 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:(1) Background: Cervical vertigo (CV) represents a controversial entity, with a prevalence ranging from reported high frequency to negation of CV existence. (2) Objectives: To assess the prevalence and cause of vertigo in patients with a manifest form of severe cervical spondylosis-degenerative cervical myelopathy (DCM) with special focus on CV. (3) Methods: The study included 38 DCM patients. The presence and character of vertigo were explored with a dedicated questionnaire. The cervical torsion test was used to verify the role of neck proprioceptors, and ultrasound examinations of vertebral arteries to assess the role of arteriosclerotic stenotic changes as hypothetical mechanisms of CV. All patients with vertigo underwent a detailed diagnostic work-up to investigate the cause of vertigo. (4) Results: Symptoms of vertigo were described by 18 patients (47%). Causes of vertigo included: orthostatic dizziness in eight (22%), hypertension in five (14%), benign paroxysmal positional vertigo in four (11%) and psychogenic dizziness in one patient (3%). No patient responded positively to the cervical torsion test or showed significant stenosis of vertebral arteries. (5) Conclusions: Despite the high prevalence of vertigo in patients with DCM, the aetiology in all cases could be attributed to causes outside cervical spine and related nerve structures, thus confirming the assumption that CV is over-diagnosed.
| S-EPMC8201049 | biostudies-literature
Project description:BackgroundDegenerative cervical myelopathy (DCM) is a poorly recognised form of spinal cord injury which arises when degenerative changes in the cervical spine injure the spinal cord. Timely surgical intervention is critical to preventing disability. Despite this, DCM is frequently undiagnosed, and may be misconstrued as normal ageing. For a disease associated with age, we hypothesised that the elderly may represent an underdiagnosed population. This study aimed to evaluate this hypothesis by comparing age-stratified estimates of DCM prevalence based on spinal cord compression (SCC) data with hospital-diagnosed prevalence in the UK.MethodsWe queried the UK Hospital Episode Statistics database for admissions with a primary diagnosis of DCM. Age-stratified incidence rates were calculated and extrapolated to prevalence by adjusting population-level life expectancy to the standardised mortality ratio of DCM. We compared these figures to estimates of DCM prevalence based on the published conversion rate of asymptomatic SCC to DCM.ResultsThe mean prevalence of DCM across all age groups was 0.19% (0.17, 0.21), with a peak prevalence of 0.42% at age 50-54 years. This contrasts with estimates from SCC data which suggest a mean prevalence of 2.22% (0.436, 2.68) and a peak prevalence of 4.16% at age > 79 years.ConclusionsTo our knowledge, this is the first study to estimate the age-stratified prevalence of DCM and estimate underdiagnosis. There is a substantial difference between estimates of DCM prevalence derived from SCC data and UK hospital activity data. This is greatest amongst elderly populations, indicating a potential health inequality.
| S-EPMC9813047 | biostudies-literature
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.
| S-EPMC7317636 | biostudies-literature
Project description:Degenerative cervical myelopathy (DCM) is a common progressive disease of the spinal cord which can cause tetraplegia. Despite its prevalence, few studies have investigated the pathophysiology of DCM. Macroautophagy is a cellular process which degrades intracellular contents and its disruption is thought to contribute to many neurodegenerative diseases. The present study tests the hypothesis that macroautophagy is impaired in DCM. To address this, we utilised a collection of post-mortem cervical spinal cord samples and investigated seven DCM cases and five human controls. Immunohistochemical staining was used to visualise proteins involved in autophagy. This demonstrated significantly reduced numbers of LC3 puncta in cases versus controls (p = 0.0424). Consistent with reduced autophagy, we identified large aggregates of p62 in four of seven cases and no controls. Tau was increased in two of five cases compared to controls. BCL-2 was significantly increased in cases versus controls (p = 0.0133) and may explain this reduction in autophagy. Increased BCL-2 (p = 0.0369) and p62 bodies (p = 0.055) were seen in more severe cases of DCM. This is the first evidence that autophagy is impaired in DCM; the impairment appears greater in more severe cases. Further research is necessary to investigate whether macroautophagy has potential as a therapeutic target in DCM.
| S-EPMC9279443 | biostudies-literature
Project description:Degenerative Cervical Myelopathy (DCM) is the most common cause of spinal cord impairment in elderly populations. It describes a spectrum of disorders that cause progressive spinal cord compression, neurological impairment, loss of bladder and bowel functions, and gastrointestinal dysfunction. The gut microbiota has been recognized as an environmental factor that can modulate both the function of the central nervous system and the immune response through the microbiota-gut-brain axis. Changes in gut microbiota composition or microbiota-producing factors have been linked to the progression and development of several pathologies. However, little is known about the potential role of the gut microbiota in the pathobiology of DCM. Here, DCM was induced in C57BL/6 mice by implanting an aromatic polyether material underneath the C5-6 laminae. The extent of DCM-induced changes in microbiota composition was assessed by 16S rRNA sequencing of the fecal samples. The immune cell composition was assessed using flow cytometry. To date, several bacterial members have been identified using BLAST against the largest collection of metagenome-derived genomes from the mouse gut. In both, female and males DCM caused gut dysbiosis compared to the sham group. However, dysbiosis was more pronounced in males than in females, and several bacterial members of the families Lachnospiraceae and Muribaculaceae were significantly altered in the DCM group. These changes were also associated with altered microbe-derived metabolic changes in propionate-, butyrate-, and lactate-producing bacterial members. Our results demonstrate that DCM causes dynamic changes over time in the gut microbiota, reducing the abundance of butyrate-producing bacteria, and lactate-producing bacteria to a lesser extent. Genome-scale metabolic modeling using gapseq successfully identified pyruvate-to-butanoate and pyruvate-to-propionate reactions involving genes such as Buk and ACH1, respectively. These results provide a better understanding of the sex-specific molecular effects of changes in the gut microbiota on DCM pathobiology.
| S-EPMC10623434 | biostudies-literature
Project description:In this study, we aim to identify and explore the diagnostic value of differentially expressed genes (DEGs) in the blood of patients with degenerative cervical myelopathy (DCM), cervical spondylotic radiculopathy (CSR), and healthy controls (HC).
2024-10-05 | GSE223227 | GEO
Project description:ObjectiveDegenerative cervical myelopathy [DCM] is a disabling and increasingly prevalent group of diseases. Heterogeneous reporting of trial outcomes limits effective inter-study comparison and optimisation of treatment. This is recognised in many fields of healthcare research. The present study aims to assess the heterogeneity of outcome reporting in DCM as the premise for the development of a standardised reporting set.MethodsA systematic review of MEDLINE and EMBASE databases, registered with PROSPERO (CRD42015025497) was conducted in accordance with PRISMA guidelines. Full text articles in English, with >50 patients (prospective) or >200 patients (retrospective), reporting outcomes of DCM were eligible.Results108 studies, assessing 23,876 patients, conducted world-wide, were identified. Reported outcome themes included function (reported by 97, 90% of studies), complications (reported by 56, 52% of studies), quality of life (reported by 31, 29% of studies), pain (reported by 29, 27% of studies) and imaging (reported by 59, 55% of studies). Only 7 (6%) studies considered all of domains in a single publication. All domains showed variability in reporting.ConclusionsSignificant heterogeneity exists in the reporting of outcomes in DCM. The development of a consensus minimum dataset will facilitate future research synthesis.
| S-EPMC4970758 | biostudies-literature
Project description:Degenerative cervical myelopathy (DCM) is a common aging condition caused by spinal cord compression. Individuals with DCM often presented with residual balance and functional impairments postoperatively. Perturbation-based balance training (PBT) has been shown to have positive effects on populations with neurological disorders but has yet to be investigated in DCM. The objective of this study was therefore to evaluate the effects of PBT on balance and functional performance in postoperative individuals with DCM. Fifteen postoperative individuals with DCM (DCM group) and 14 healthy adults (healthy control group) were recruited. The DCM group received a 4-weeks PBT using a perturbation treadmill. The outcome measures included mean velocity of center of pressure (COP) during quiet standing; center of mass (COM) variance and reaction time to balance perturbation during standing with forward and backward perturbation; gait speed during level ground walking; Timed Up and Go Test (TUG) and disability questionnaire scores including Visual Analog Scale, Neck Disability Index, and Lower Extremity Function of Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire. The assessments were conducted pre- and post-training postoperatively for the DCM group but only once for the healthy control group. Significant improvements were observed in the mean velocity of COP, COM variance, reaction time, gait speed, and TUG in the DCM group. Disability questionnaire scores were not significantly different after training in DCM group. For between-group comparisons, significant differences that were observed pre-training were not observed post-training. The 4-weeks PBT is a potential rehabilitation strategy for addressing balance and functional impairment in postoperative individuals with DCM. In addition, the post-training performance in the DCM group exhibited trends comparable to those of age-matched healthy controls. Furthermore, the training regimens offer a practical reference for future studies on populations with balance disorders. Future studies complemented with neurophysiological assessments could reveal more information of the underlying mechanisms of PBT.
| S-EPMC7044125 | biostudies-literature
Project description:Study designCohort study.ObjectiveWe aimed to evaluate the associations of genetic and nongenetic factors with degenerative cervical myelopathy (DCM).Summary of background dataThere 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 methodsUsing 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.ResultsA 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.ConclusionsIncreasing 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 evidencePrognostic level III.
| S-EPMC10524420 | biostudies-literature
Project description:BackgroundDegenerative cervical myelopathy (DCM) is a common and disabling condition. Early effective treatment is limited by late diagnosis. Conventional descriptions of DCM focus on motor and sensory limb disability, however, recent work suggests the true impact is much broader. This study aimed to characterise the symptomatic presentation of DCM from the perspective of people with DCM and determine whether any of the reported symptoms, or groups of symptoms, were associated with early diagnosis.MethodsAn internet survey was developed, using an established list of patient-reported effects. Participants (N = 171) were recruited from an online community of people with DCM. Respondents selected their current symptoms and primary presenting symptom. The relationship of symptoms and their relationship to time to diagnosis were explored. This included symptoms not commonly measured today, termed 'non-conventional' symptoms.ResultsAll listed symptoms were experienced by >10% of respondents, with poor balance being the most commonly reported (84.2%). Non-conventional symptoms accounted for 39.7% of symptomatic burden. 55.4% of the symptoms were reported as an initial symptom, with neck pain the most common (13.5%). Non-conventional symptoms accounted for 11.1% of initial symptoms. 79.5% of the respondents were diagnosed late (>6 months). Heavy legs was the only initial symptom associated with early diagnosis.ConclusionsA comprehensive description of the self-reported effects of DCM has been established, including the prevalence of symptoms at disease presentation. The experience of DCM is broader than suggested by conventional descriptions and further exploration of non-conventional symptoms may support earlier diagnosis.
| S-EPMC10065274 | biostudies-literature