The influence of ApoE4 on the clinical outcomes and pathophysiology of degenerative cervical myelopathy.
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SUBMITTER: Desimone A
PROVIDER: S-EPMC8410082 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:INTRODUCTION:Degenerative Cervical Myelopathy [DCM] often presents with non-specific symptoms and signs. It progresses insidiously and leads to permanent neurological dysfunction. Decompressive surgery can halt disease progression, however significant delays in diagnosis result in increased disability and limit recovery. The nature of early DCM symptoms is unknown, moreover it has been suggested incomplete examination contributes to missed diagnosis. This study examines how DCM is currently assessed, if assessment differs between stages of healthcare, and whether this influences patient management. STUDY DESIGN:Retrospective cohort study. METHODS:Cervical MRI scans (N = 1123) at a tertiary neurosciences center, over a single year, were screened for patients with DCM (N = 43). Signs, symptoms, and disease severity of DCM were extracted from patient records. Patients were considered at 3 phases of clinical assessment: primary care, secondary care, and surgical assessment. RESULTS:Upper limb paraesthesia and urinary dysfunction were consistently the most and least prevalent symptoms respectively. Differences between assessing clinicians were present in the reporting of: limb pain (p<0.005), objective limb weakness (p = 0.01), hyperreflexia (p<0.005), Hoffmann reflex (p<0.005), extensor plantar reflex (p = 0.007), and lower limb spasticity (p<0.005). Pathological reflexes were least frequently assessed by primary care doctors. CONCLUSION:DCM assessment varies significantly between assessors. Reporting of key features of DCM is especially low in primary care. Incomplete assessment may hinder early diagnosis and referral to spinal surgery.
| S-EPMC6296508 | biostudies-literature
Project description: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.
| S-EPMC7203415 | biostudies-literature
Project description:Study designA prospective observational international study.ObjectiveThe aim of this study was to evaluate outcomes of decompressive surgery in patients with very severe degenerative cervical myelopathy (DCM).Summary of background dataAlthough decompressive surgery has been evidenced as a safe and effective approach for patients with myelopathic deficiencies, studies have suggested residual disability following treatment in patients with more severe disease presentation.MethodsPostoperative outcomes of 60 patients with very severe DCM (modified Japanese Orthopaedic Association [mJOA] score ≤8) were compared to outcomes of 188 patients with severe DCM (mJOA 9-11). Postimputation follow-up rate was 93.1%. Unadjusted and adjusted analyses were performed using two-way repeated measures of covariance.ResultsThe two cohorts were similar in demographics, length of duration of myelopathy symptoms, source of stenosis, and surgical approaches used to decompress the spine. The very severe and severe cohorts differed in preoperative Nurick grades (4.97 vs. 3.91, respectively, P < 0.0001) and Neck Disability Index scores (45.20 vs. 56.21, respectively, P = 0.0006). There were no differences in Short Form 36 (SF-36v2) physical (PCS) and mental (MCS) component summary scores. Both cohorts improved in mJOA, Nurick, Neck Disability Index, and SF-36v2 PCS and MCS scores. Despite the substantial postoperative improvements, patients in both cohorts had considerable residual symptoms. Two-thirds of the patients in the very severe cohort had severe (mJOA ≤11) or moderate (mJOA ≤ 14) myelopathy symptoms at 24 months follow-up. Longer duration of disease was associated with poorer treatment response.ConclusionDecompressive surgery is effective in patients with very severe DCM; however, patients have significant residual symptoms and disability. The very severe subgroup (mJOA ≤8) of patients with DCM represents a distinct group of patients and their different clinical trajectory is important for clinicians and patients to recognize. Duration of symptoms negatively affects chances for recovery. Whenever possible, patients with DCM should be treated before developing very severe symptomatology.Level of evidence2.
| S-EPMC6066419 | biostudies-literature
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: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), 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.
| S-EPMC8001572 | biostudies-literature