Respiratory dysfunction in degenerative cervical myelopathy: A systematic review.

INTRODUCTION: Degenerative cervical myelopathy is a condition of symptomatic cervical spinal cord compression secondary to a range of degenerative spinal pathology. Respiratory symptoms such as shortness of breath are not uncommonly reported by people with DCM and respiratory dysfunction has been described in several DCM studies. The objective of this review was therefore to systematically synthesise the current evidence on the relationship between DCM and respiratory function. METHODS: The review was registered on PROSPERO and adhered to PRISMA guidelines. Ovid MEDLINE and Embase were searched from inception to 14th March 2023. DCM studies reporting on any measure or outcome relating to respiratory function or disease were eligible. Reference lists of included studies and relevant reviews articles were hand searched. Title, abstract and full text screening, risk of bias and GRADE assessments were completed in duplicate. A quantitative synthesis is presented. RESULTS: Of 1991 studies identified by literature searching, 13 met inclusion criteria: 3 cohort studies, 5 case-control studies, 1 case series and 4 case studies. Forced vital capacity (FVC), peak expiratory flow rate (PEFR) and maximal voluntary ventilation (MVV) were reported to be lower in DCM patients than controls; there was inconsistency in comparisons of forced expiratory volume in 1 s (FEV1). There was conflicting evidence on whether surgical decompression was associated with improvements in respiratory parameters and on the relationship between level of spinal cord compression and respiratory dysfunction. CONCLUSION: DCM may be associated with respiratory dysfunction. However, consistency and quality of evidence is currently low. Further work should characterise respiratory dysfunction in DCM patients more rigorously and investigate putative mechanisms such as disruption to cervical nerve roots responsible for diaphragmatic innervation and damage to descending spinal projections from brainstem respiratory centres.

The incidence and impact of 'Tandem Neurotrauma'.

Introduction: The epidemiology and prognosis of the isolated traumatic brain injury (TBI) and spinal cord injury (SCI) are well studied. However, the knowledge of the impact of concurrent neurotrauma is very limited. Research questions: To characterize the longitudinal incidence of concurrent TBI and SCI and to investigate their combined impact on clinical care and outcomes, compared to a comparative but isolated SCI or TBI. Materials and methods: Data from 167,793 patients in the Trauma Audit and Research Network (TARN) registry collected in England and Wales between 2008 and 2018 were analysed. Tandem neurotrauma was defined as patients with concurrent TBI and SCI. The patient with isolated TBI or SCI was matched to the patient with tandem neurotrauma using propensity scores. Results: The incidence of tandem neurotrauma increased tenfold between 2008 and 2018, from 0.21 to 2.21 per 100,000 person-years. Patients in the tandem neurotrauma group were more likely to require multiple surgeries, ICU admission, longer ICU and hospital LOS, higher 30-day mortality, and were more likely to be transferred to acute hospitals and rehabilitation or suffer death at discharge, compared to patients with isolated TBI. Likewise, individuals with tandem neurotrauma compared to those with isolated SCI had a higher tendency to receive more than one surgery, ICU admission, longer LOS for ICU and higher mortality either at 30-day follow-up or at discharge. Discussion and conclusions: The incidence of tandem neurotrauma has increased steadily during the past decade. Its occurrence leads to greater mortality and care requirements, particularly when compared to TBI alone. Further investigations are warranted to improve outcomes in tandem neurotrauma.

Utility of 5-ALA for resection of CNS tumours other than high-grade gliomas: a protocol for a systematic review.

INTRODUCTION: 5-aminolevulinic acid (5-ALA) is a proagent developed for fluorescent-guided surgery for high-grade glioma patients associated with a significant increase in resection conferring survival. 5-ALA was shown to penetrate the blood-brain barrier accumulating in malignant glioma cells with high selectivity, sensitivity and positive predictive value. However, those have yet to be explored aiding diagnosis for tumours of the central nervous system (CNS) other than high-grade gliomas (HGG). No up-to-date systematic review exists reporting the major surgical outcomes and diagnostic accuracy. We sought to conduct a systematic review of the literature summarising surgical outcomes, evaluate the quality of diagnostic accuracy reported in the literature and qualitatively assess the evidence to inform future studies. METHODS AND ANALYSIS: We will search electronic databases (Medline, Embase) with subsequent interrogation of references lists of articles reporting the use of 5-ALA for brain tumours other than high-grade glioma adult patients, which also report the extent of resection and/or survival. Prospective and retrospective cohort and case-control studies with more than five patients will be included. Two independent reviewers will screen the abstracts and full articles, with a third reviewer resolving any conflicts. The data will be extracted in a standardised template and outcomes will be reported using descriptive statists. The quality of non-randomised studies will be appraised. ETHICS AND DISSEMINATION: The study will summarise the available evidence on the effect of the clinical utility of 5-ALA in achieving resection and improving survival and its diagnostic accuracy for tumours of the CNS other than HGG. The data will be presented nationally and internationally and the manuscript will be published in a peer-reviewed journal. No ethical approvals were needed. The aim is to inform prospective studies minimising reporting bias allowing for more reliable, reproducible and generalisable results. The study has been registered in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.PROSPERO registration numberCRD42021260542.

Developing Novel Therapies for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 7]: Opportunities From Restorative Neurobiology.

STUDY DESIGN: Narrative review. OBJECTIVES: To provide an overview of contemporary therapies for the James Lind Alliance priority setting partnership for degenerative cervical myelopathy (DCM) question: 'Can novel therapies, including stem-cell, gene, pharmacological and neuroprotective therapies, be identified to improve the health and wellbeing of people living with DCM and slow down disease progression?' METHODS: A review of the literature was conducted to outline the pathophysiology of DCM and present contemporary therapies that may hold therapeutic value in 3 broad categories of neuroprotection, neuroregeneration, and neuromodulation. RESULTS: Chronic spinal cord compression leads to ischaemia, neuroinflammation, demyelination, and neuronal loss. Surgical intervention may halt progression and improve symptoms, though the majority do not make a full recovery leading to lifelong disability. Neuroprotective agents disrupt deleterious secondary injury pathways, and one agent, Riluzole, has undergone Phase-III investigation in DCM. Although it did not show efficacy on the primary outcome modified Japanese Orthopaedic Association scale, it showed promising results in pain reduction. Regenerative approaches are in the early stage, with one agent, Ibudilast, currently in a phase-III investigation. Neuromodulation approaches aim to therapeutically alter the state of spinal cord excitation by electrical stimulation with a variety of approaches. Case studies using electrical neuromuscular and spinal cord stimulation have shown positive therapeutic utility. CONCLUSION: There is limited research into interventions in the 3 broad areas of neuroprotection, neuroregeneration, and neuromodulation for DCM. Contemporary and novel therapies for DCM are now a top 10 priority, and whilst research in these areas is limited in DCM, it is hoped that this review will encourage research into this priority.

A New Framework for Investigating the Biological Basis of Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 5]: Mechanical Stress, Vulnerability and Time.

STUDY DESIGN: Literature Review (Narrative). OBJECTIVE: To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5. METHODS: Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual's susceptibility, including the proposal of a new framework. RESULTS: Present pathobiological and mechanistic knowledge does not adequately explain the disease phenotype; why only a subset of patients with visualized cord compression show clinical myelopathy, and the amount of cord compression only weakly correlates with disability. We propose that DCM is better represented as a function of several interacting mechanical forces, such as shear, tension and compression, alongside an individual's vulnerability to spinal cord injury, influenced by factors such as age, genetics, their cardiovascular, gastrointestinal and nervous system status, and time. CONCLUSION: Understanding the disease pathobiology is a fundamental research priority. We believe a framework of mechanical stress, vulnerability, and time may better represent the disease as a whole. Whilst this remains theoretical, we hope that at the very least it will inspire new avenues of research that better encapsulate the full spectrum of disease.

Improving Assessment of Disease Severity and Strategies for Monitoring Progression in Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 4].

STUDY DESIGN: Narrative Review. OBJECTIVE: To (i) discuss why assessment and monitoring of disease progression is critical in Degenerative cervical myelopathy (DCM); (ii) outline the important features of an ideal assessment tool and (iii) discuss current and novel strategies for detecting subtle deterioration in DCM. METHODS: Literature review. RESULTS: Degenerative cervical myelopathy is an overarching term used to describe progressive injury to the cervical spinal cord by age-related changes of the spinal axis. Based on a study by Smith et al (2020), the prevalence of DCM is approximately 2.3% and is expected to rise as the global population ages. Given the global impact of this disease, it is essential to address important knowledge gaps and prioritize areas for future investigation. As part of the AO Spine RECODE-DCM (Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy) project, a priority setting partnership was initiated to increase research efficiency by identifying the top ten research priorities for DCM. One of the top ten priorities for future DCM research was: What assessment tools can be used to evaluate functional impairment, disability and quality of life in people with DCM? What instruments, tools or methods can be used or developed to monitor people with DCM for disease progression or improvement either before or after surgical treatment? CONCLUSIONS: With the increasing prevalence of DCM, effective surveillance of this population will require both the implementation of a monitoring framework as well as the development of new assessment tools.

A survey of teaching undergraduate neuroanatomy in the United Kingdom and Ireland.

BACKGROUND: Medical students' perception of neuroanatomy as a challenging topic has implications for referrals and interaction with specialists in the clinical neurosciences. Given plans to introduce a standardised Medical Licensing Assessment by 2023, it is important to understand the current framework of neuroanatomy education. This study aims to describe how neuroanatomy is taught and assessed in the UK and Ireland. METHODS: A structured questionnaire capturing data about the timing, methods, materials, assessment and content of the 2019/2020 neuroanatomy curriculum in the UK and Ireland medical schools. RESULTS: We received 24/34 responses. Lectures (96%) were the most widely used teaching method, followed by prosection (80%), e-learning (75%), tutorials/seminars (67%), problem-based learning (50%), case-based learning (38%), and dissection (30%). The mean amount of core neuroanatomy teaching was 29.3 hours. The most common formats of assessing neuroanatomical knowledge were multiple-choice exams, spot tests, and objective structured clinical exams. Only 37.5% schools required demonstration of core clinical competency relating to neuroanatomy. CONCLUSIONS: Our survey demonstrates variability in how undergraduate neuroanatomy is taught and assessed across the UK and Ireland. There is a role for development and standardisation of national undergraduate neuroanatomy curricula in order to improve confidence and attainment.

The Relative Merits of Posterior Surgical Treatments for Multi-Level Degenerative Cervical Myelopathy Remain Uncertain: Findings from a Systematic Review.

OBJECTIVES: To assess the reporting of study design and characteristics in multi-level degenerative cervical myelopathy (DCM) treated by posterior surgical approaches, and perform a comparison of clinical and radiographic outcomes between different approaches. METHODS: A literature search was performed in Embase and MEDLINE between 1995-2019 using a sensitive search string combination. Studies were selected by predefined selection criteria: Full text articles in English, with >10 patients (prospective) or >50 patients (retrospective), reporting outcomes of multi-level DCM treated by posterior surgical approach. RESULTS: A total of 75 studies involving 19,510 patients, conducted worldwide, were identified. Laminoplasty was described in 56 studies (75%), followed by laminectomy with (36%) and without fusion (16%). The majority of studies were conducted in Asia (84%), in the period of 2016-2019 (51%), of which laminoplasty was studied predominantly. Twelve (16%) prospective studies and 63 (84%) retrospective studies were identified. The vast majority of studies were conducted in a single centre (95%) with clear inclusion/exclusion criteria and explicit cause of DCM. Eleven studies (15%) included patients with ossification of the posterior longitudinal ligament exclusively with cohorts of 57 to 252. The clinical and radiographic outcomes were reported with heterogeneity when comparing laminoplasty, laminectomy with and without fusion. CONCLUSIONS: Heterogeneity in the reporting of study and sample characteristics exists, as well as in clinical and radiographic outcomes, with a paucity of studies with a higher level of evidence. Future studies are needed to elucidate the clinical effectiveness of posterior surgical treatments.

Therapeutic repetitive Transcranial Magnetic stimulation (rTMS) for neurological dysfunction in Degenerative cervical Myelopathy: An unexplored opportunity? Findings from a systematic review.

Degenerative Cervical Myelopathy (DCM) is one of the commonest causes of non-traumatic Spinal Cord Injury (SCI) leading to significant neurological impairments and reduced health-related quality of life. Guidelines recommend surgical intervention to halt disease progression in moderate-to-severe cases, and whilst many do experience neurological recovery, this is incomplete leading to lifelong disability. A James Lind Alliance (JLA) research priority setting partnership for DCM highlighted novel therapies and rehabilitation as top 10 research priority in DCM. Neurological recovery following decompressive surgery in DCM has been attributed neuroplasticity, and therapies influencing neuroplasticity are of interest. Electrical neuromodulation interventions such as repetitive Transcranial Magnetic Stimulation (rTMS), are being increasingly explored in related fields such as spinal cord injury to improve recovery and symptoms. The aim of this systematic review was to determine the role and efficacy of rTMS as a therapeutic tool in managing neurological dysfunction in DCM. We searched the databases of Medline, EMBASE, CINAHIL and Cochrane Central Register of Controlled Trials (CENTRAL). No studies were identified that had investigated the therapeutic use of rTMS in DCM. A significant number of studies had explored TMS based neurophysiological assessments indicating its role as a screening and prognostication tool in DCM. Post-operative rehabilitation interventions including TMS and non-operative management of DCM is a field which requires further investigation, as required in the AO Spine JLA DCM research priorities. rTMS is a safe neuromodulatory intervention and may have a role in enhancing recovery in DCM. Further research in these fields are required.

High incidence of spring ligament laxity in ankle fractures with complete deltoid ruptures and secondary first ray instability.

AIMS: To assess the incidence of spring ligament failure in patients who have complete deltoid ruptures. PATIENTS AND METHODS: The authors retrospectively analysed ankle fractures in our trauma database from January 2015 to January 2019. 61 patients who sustained ankle fractures with complete deltoid ligament ruptures based on an AP ankle radiographs with increased medial joint space were identified. 25 patients attended clinic for assessment. Of these, 5 were found to have gross planovalgus with pre-existing spring ligament laxity in the uninjured control foot and these were excluded from the analysis. 20 patients were assessed for spring ligament failure /laxity. For each patient, the uninjured foot was used as the control. RESULTS: The TMT instability score and the lateral translation score showed statistically significant increases in the injured compared to the uninjured foot. The ratio of increase in both TMT instability and lateral translation scores (strain) in the injured versus the uninjured foot was assessed. A strong correlation (+0.62 pearson correlation coefficient) was found between the two ratios. CONCLUSION: All 20 patients showed increased spring ligament laxity and 19 patients showed increased TMT instability. Our results show that with complete deltoid rupture, there is likely greater disruption of the medial ligamentous structures of the foot than previously recognised. The degree of increase in the spring ligament strain also correlates with the degree of strain at the plantar TMT joint ligaments, and thus first ray instability. This finding has significant implications for the long-term assessment and management of ankle fractures involving complete deltoid disruption. Early intervention with orthotics in this cohort may prevent progressive destabilisation of the midfoot and the first ray. This evolving understanding may lead to the prospect of earlier surgical intervention to reconstitute the integrity of the spring ligament and protect the foot progressing to stage 2 AAFD.

How common is repeat surgery and multi-level treatment in Degenerative Cervical Myelopathy? Findings from a patient perspective survey.

Degenerative Cervical Myelopathy (DCM) is a common condition which causes significant disability and reduces health-related quality of life. The only evidence-based treatment and current management guidance is surgery to decompress the spinal cord and stop further damage in moderate to severe cases. However, this guidance is mainly informed by studies that only include first time surgery and/or single level disease, but DCM can reoccur after primary surgery and affect multiple levels of the spine. It is unclear whether patients in these subgroups; repeat surgery and multi-level DCM, differ significantly in their baseline and disease characteristics from those with single-level, single-operation disease. To investigate this, we conducted an online survey of people with DCM looking at key demographic, disease (e.g. mJOA) and treatment characteristics. We received a total of 778 respondents, of which 159 (20%) had undergone surgery for DCM. Around 75% of these respondents had a single operation and 65% at a single level. We found no statistically significant difference in key participant and disease characteristics between respondents with single-level or single-operation and those with multi-level DCM or multiple operations. These data support generalisability of research to these subgroups but also warrants further investigations as these subgroups are underrepresented in current research.

Traumatic atlantoaxial rotatory subluxation in adults - A case report and literature review.

BACKGROUND: Traumatic atlantoaxial rotatory subluxation (AARS) is extremely rare in adult versus pediatric populations. Patients usually present with post-traumatic neck pain and torticollis. Surgical management aims at reducing the deformity and stabilizing the spine utilizing external orthotics, and/or internal reduction/fixation. METHODS: A 65-year-old female fell downstairs at home. She complained of neck pain with right-sided tenderness and torticollis. The radiographic studies and CT scan demonstrated AARS. This led to an emergent open reduction with internal fixation at the C1-C2 level. RESULTS: We identified 25 similar cases of AARS in the English literature. Patients averaged 28.7 years of age and mostly sustained motor vehicle accidents largely treated with traction/orthotics; only six patients required surgical open reduction/internal fixation. CONCLUSION: In this case, the patient's C1-C2 deformity required open reduction/internal fixation rather than bracing alone.

Intermittent theta-burst stimulation for upper-limb dysfunction and spasticity in spinal cord injury: a single-blind randomized feasibility study.

STUDY DESIGN: Single-blind, sham-controlled, crossover randomized feasibility study OBJECTIVES: (1) Assess the feasibility of a full-scale trial of intermittent theta-burst stimulation (iTBS) for upper-limb sensorimotor dysfunction following spinal cord injury (SCI). (2) Determine the safety and tolerability of iTBS over primary motor cortex on upper-limb function in people with spinal cord injury (SCI). SETTING: Large Tertiary Spinal Injuries Centre METHODS: Participants with incomplete SCI, suffering with upper-limb spasticity were recruited and randomized to receive active/sham iTBS over the hand representation of the primary motor cortex. The intervention was delivered in 10 sessions over a 2-week period, followed by a 2-week washout, before being crossed over to receive the alternative intervention for the same number of sessions. Feasibility was assessed by pre-specified criteria which included recruitment rate of 3 participants per month, 10 completed interventions and 10 complete data sets for 15 recruited participants with no serious adverse events. Secondary outcomes included preliminary data collection for spasticity, pain and sensorimotor function. RESULTS: Twelve participants were recruited over 10 weeks (i.e., 4.8 per month), with 11 randomized and 10 completing the intervention protocol with no serious adverse events. Eight complete data sets were obtained as two participants failed to attend follow-up. Data from 10 participants were analyzed, with one early dropout due to an unrelated adverse event. CONCLUSIONS: It is safe and feasible to conduct a full-scale trial. Whilst iTBS has shown promising results, further research optimizing the intervention is required to improve anticipated clinical efficacy.