Acute quadriplegia and death following a routine MRI for undiagnosed degenerative cervical myelopathy.

Bilateral upper limb paraesthesia and pain are common symptoms of degenerative cervical myelopathy (DCM). Such symptoms instigate investigation by cervical spine magnetic resonance imaging (MRI). This was the case for our patient, who was 72-years-in age and otherwise fit and well. During the scan he unfortunately developed sudden onset quadriplegia secondary to an intervertebral disc prolapse. This necessitated intubation due to respiratory failure and urgent transfer to the neurosciences critical care unit at a tertiary neurosciences centre. Despite prompt surgical decompression, he did not regain function. Extubation was unsuccessful on three occasions. Following discussion between the patient and his family, ventilation was withdrawn, and he died the following day. This case highlights the potentially devastating consequences of DCM and poses questions about the aetiology of DCM.

Finite Element Analysis for Degenerative Cervical Myelopathy: Scoping Review of the Current Findings and Design Approaches, Including Recommendations on the Choice of Material Properties.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a slow-motion spinal cord injury caused via chronic mechanical loading by spinal degenerative changes. A range of different degenerative changes can occur. Finite element analysis (FEA) can predict the distribution of mechanical stress and strain on the spinal cord to help understand the implications of any mechanical loading. One of the critical assumptions for FEA is the behavior of each anatomical element under loading (ie, its material properties). OBJECTIVE: This scoping review aims to undertake a structured process to select the most appropriate material properties for use in DCM FEA. In doing so, it also provides an overview of existing modeling approaches in spinal cord disease and clinical insights into DCM. METHODS: We conducted a scoping review using qualitative synthesis. Observational studies that discussed the use of FEA models involving the spinal cord in either health or disease (including DCM) were eligible for inclusion in the review. We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The MEDLINE and Embase databases were searched to September 1, 2021. This was supplemented with citation searching to retrieve the literature used to define material properties. Duplicate title and abstract screening and data extraction were performed. The quality of evidence was appraised using the quality assessment tool we developed, adapted from the Newcastle-Ottawa Scale, and shortlisted with respect to DCM material properties, with a final recommendation provided. A qualitative synthesis of the literature is presented according to the Synthesis Without Meta-Analysis reporting guidelines. RESULTS: A total of 60 papers were included: 41 (68%) "FEA articles" and 19 (32%) "source articles." Most FEA articles (33/41, 80%) modeled the gray matter and white matter separately, with models typically based on tabulated data or, less frequently, a hyperelastic Ogden variant or linear elastic function. Of the 19 source articles, 14 (74%) were identified as describing the material properties of the spinal cord, of which 3 (21%) were considered most relevant to DCM. Of the 41 FEA articles, 15 (37%) focused on DCM, of which 9 (60%) focused on ossification of the posterior longitudinal ligament. Our aggregated results of DCM FEA indicate that spinal cord loading is influenced by the pattern of degenerative changes, with decompression alone (eg, laminectomy) sufficient to address this as opposed to decompression combined with other procedures (eg, laminectomy and fusion). CONCLUSIONS: FEA is a promising technique for exploring the pathobiology of DCM and informing clinical care. This review describes a structured approach to help future investigators deploy FEA for DCM. However, there are limitations to these recommendations and wider uncertainties. It is likely that these will need to be overcome to support the clinical translation of FEA to DCM.

The significance of metabolic disease in degenerative cervical myelopathy: a systematic review.

Introduction: Degenerative cervical myelopathy (DCM) is a form of chronic spinal cord injury, with a natural history of potential for progression over time. Whilst driven by mechanical stress on the spinal cord from degenerative and congenital pathology, the neurological phenotype of DCM is likely to be modified by multiple systemic factors. The role of metabolic factors is therefore of interest, particularly given that ischaemia is considered a key pathological mechanism of spinal cord injury. The objective was therefore to synthesise current evidence on the effect of metabolism on DCM susceptibility, severity, and surgical outcomes. Methods: A systematic review in MEDLINE and Embase was conducted following PRISMA guidelines. Full-text papers in English, with a focus on DCM and metabolism, including diabetes, cardiovascular disease, anaemia, and lipid profile, were eligible for inclusion. Risk of methodological bias was assessed using the Joanna Briggs Institute (JBI) critical assessment tools. Quality assessments were performed using the GRADE assessment tool. Patient demographics, metabolic factors and the relationships between metabolism and spinal cord disease, spinal column disease and post-operative outcomes were assessed. Results: In total, 8,523 papers were identified, of which 57 met criteria for inclusion in the final analysis. A total of 91% (52/57) of included papers assessed the effects of diabetes in relation to DCM, of which 85% (44/52) reported an association with poor surgical outcomes; 42% of papers (24/57) discussed the association between cardiovascular health and DCM, of which 88% (21/24) reported a significant association. Overall, DCM patients with diabetes or cardiovascular disease experienced greater perioperative morbidity and poorer neurological recovery. They were also more likely to have comorbidities such as obesity and hyperlipidaemia. Conclusion: Metabolic factors appear to be associated with surgical outcomes in DCM. However, evidence for a more specific role in DCM susceptibility and severity is uncertain. The pathophysiology and natural history of DCM are critical research priorities; the role of metabolism is therefore a key area for future research focus. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021268814.

Brain MRI changes in degenerative cervical myelopathy: a systematic review.

BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction globally. Associated neurological symptoms and signs have historically been explained by pathobiology within the cervical spine. However, recent advances in imaging have shed light on numerous brain changes in patients with DCM, and it is hypothesised that these changes contribute to DCM pathogenesis. The aetiology, significance, and distribution of these supraspinal changes is currently unknown. The objective was therefore to synthesise all current evidence on brain changes in DCM. METHODS: A systematic review was performed. Cross-sectional and longitudinal studies with magnetic resonance imaging on a cohort of patients with DCM were eligible. PRISMA guidelines were followed. MEDLINE and Embase were searched to 28th August 2023. Duplicate title/abstract screening, data extraction and risk of bias assessments were conducted. A qualitative synthesis of the literature is presented as per the Synthesis Without Meta-Analysis (SWiM) reporting guideline. The review was registered with PROSPERO (ID: CRD42022298538). FINDINGS: Of the 2014 studies that were screened, 47 studies were identified that used MRI to investigate brain changes in DCM. In total, 1500 patients with DCM were included in the synthesis, with a mean age of 53 years. Brain alterations on MRI were associated with DCM both before and after surgery, particularly within the sensorimotor network, visual network, default mode network, thalamus and cerebellum. Associations were commonly reported between brain MRI alterations and clinical measures, particularly the Japanese orthopaedic association (JOA) score. Risk of bias of included studies was low to moderate. INTERPRETATION: The rapidly expanding literature provides mounting evidence for brain changes in DCM. We have identified key structures and pathways that are altered, although there remains uncertainty regarding the directionality and clinical significance of these changes. Future studies with greater sample sizes, more detailed phenotyping and longer follow-up are now needed. FUNDING: ODM is supported by an Academic Clinical Fellowship at the University of Cambridge. BMD is supported by an NIHR Clinical Doctoral Fellowship at the University of Cambridge (NIHR300696). VFJN is supported by an NIHR Rosetrees Trust Advanced Fellowship (NIHR302544). This project was supported by an award from the Rosetrees Foundation with the Storygate Trust (A2844).

Novel paraneoplastic mechanism for cerebellar ataxia in Erdheim-Chester disease.

We report a case of BRAF-mutation positive Erdheim-Chester disease presenting with a cerebellar ataxia. This is the first such case to be reported without structural MRI abnormalities but with a single intrathecally produced oligoclonal band. Now that the histiocytoses have been recharacterised as neoplastic, we speculate that the mechanism of the ataxia in our case is paraneoplastic. We highlight the importance of searching for BRAF mutations in this disease, as their presence leads to effective personalised treatments.

Meeting the Shared Goals of a Student-Selected Component: Pilot Evaluation of a Collaborative Systematic Review.

BACKGROUND: Research methodology is insufficiently featured in undergraduate medical curricula. Student-selected components are designed to offer some research opportunities but frequently fail to meet student or supervisor expectations, such as completion or publication. We hypothesized that a collaborative, educational approach to a systematic review (SR), whereby medical students worked together, may improve student experience and increase success. OBJECTIVE: This study aimed to establish whether offering a small team of students the opportunity to take part in the screening phase of SRs led by an experienced postgraduate team could enhance the learning experience of students, overcome the barriers to successful research engagement, and deliver published output. METHODS: Postgraduate researchers from the University of Cambridge led a team of 14 medical students to work on 2 neurosurgical SRs. One student was appointed as the lead for each SR. All students were provided with training on SR methodology and participated in title and abstract screening using Rayyan software. Students completed prepilot, midscreening, and postscreening questionnaires on their research background, perceptions, knowledge, confidence, and experience. Questions were scored on a Likert scale of 1 (strongly disagree) to 10 (strongly agree). RESULTS: Of the 14 students involved, 29% (n=4) reported that they had received sufficient training in research methodology at medical school. Positive trends in student knowledge, confidence, and experience of SR methodology were noted across the 3 questionnaire time points. Mean responses to "I am satisfied with the level of guidance I am receiving," "I am enjoying being involved in the SR process," and "I could not gain this understanding of research from passive learning e.g., textbook or lecture" were greater than 8.0 at all time points. Students reported "being involved in this research has made me more likely to do research in the future" (mean 8.57, SD 1.50) and that "this collaborative SR improved my research experience" (mean 8.50, SD 1.56). CONCLUSIONS: This collaborative approach appears to be a potentially useful method of providing students with research experience; however, it requires further evaluation.

The impact of phosphodiesterase inhibition on neurobehavioral outcomes in preclinical models of traumatic and non-traumatic spinal cord injury: a systematic review.

Study design: Systematic review. Objective: The objective of this study was to evaluate the impact of phosphodiesterase (PDE) inhibitors on neurobehavioral outcomes in preclinical models of traumatic and non-traumatic spinal cord injury (SCI). Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered with PROSPERO (CRD42019150639). Searches were performed in MEDLINE and Embase. Studies were included if they evaluated the impact of PDE inhibitors on neurobehavioral outcomes in preclinical models of traumatic or non-traumatic SCI. Data were extracted from relevant studies, including sample characteristics, injury model, and neurobehavioral assessment and outcomes. Risk of bias was assessed using the SYRCLE checklist. Results: The search yielded a total of 1,679 studies, of which 22 met inclusion criteria. Sample sizes ranged from 11 to 144 animals. PDE inhibitors used include rolipram (n = 16), cilostazol (n = 4), roflumilast (n = 1), and PDE4-I (n = 1). The injury models used were traumatic SCI (n = 18), spinal cord ischemia (n = 3), and degenerative cervical myelopathy (n = 1). The most commonly assessed outcome measures were Basso, Beattie, Bresnahan (BBB) locomotor score (n = 13), and grid walking (n = 7). Of the 22 papers that met the final inclusion criteria, 12 showed a significant improvement in neurobehavioral outcomes following the use of PDE inhibitors, four papers had mixed findings and six found PDE inhibitors to be ineffective in improving neurobehavioral recovery following an SCI. Notably, these findings were broadly consistent across different PDE inhibitors and spinal cord injury models. Conclusion: In preclinical models of traumatic and non-traumatic SCI, the administration of PDE inhibitors appeared to be associated with statistically significant improvements in neurobehavioral outcomes in a majority of included studies. However, the evidence was inconsistent with a high risk of bias. This review provides a foundation to aid the interpretation of subsequent clinical trials of PDE inhibitors in spinal cord injury. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150639, identifier: CRD42019150639.