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Background: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research., Methods and Findings: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery., Conclusions: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Davies et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord dysfunction worldwide, for which surgery is the mainstay of treatment. At present, there is limited literature on the costs associated with the surgical management of DCM, and none from the United Kingdom (UK). This study aimed to evaluate the cost-effectiveness of DCM surgery within the National Health Service, UK., Materials and Methods: Incidence of DCM was identified from the Hospital Episode Statistics (HES) database for a single year using five ICD-10 diagnostic codes to represent DCM. Health Resource Group (HRG) data was used to estimate the mean incremental surgery (treatment) costs compared to non-surgical care, and the incremental effect (quality adjusted life year (QALY) gain) was based on data from a previous study. A cost per QALY value of <£30,000/QALY (GBP) was considered acceptable and cost-effective, as per the National Institute for Health and Clinical Excellence (NICE) guidance. A sensitivity analysis was undertaken (±5%, ±10% and ±20%) to account for variance in both the cost of admission and QALY gain., Results: The total number of admissions for DCM in 2018 was 4,218. Mean age was 62 years, with 54% of admissions being of working age (18-65 years). The overall estimated cost of admissions for DCM was £38,871,534 for the year. The mean incremental (per patient) cost of surgical management of DCM was estimated to be £9,216 (ranged £2,358 to £9,304), with a QALY gain of 0.64, giving an estimated cost per QALY value of £14,399/QALY. Varying the QALY gain by ±20%, resulted in cost/QALY figures between £12,000 (+20%) and £17,999 (-20%)., Conclusions: Surgery is estimated to be a cost-effective treatment of DCM amongst the UK population.

Study Design: Modified DELPHI Consensus Process., Objective: To agree a single unifying term and definition. Globally, cervical myelopathy caused by degenerative changes to the spine is known by over 11 different names. This inconsistency contributes to many clinical and research challenges, including a lack of awareness., Method: AO Spine RECODE-DCM (Research objectives and Common Data Elements Degenerative Cervical Myelopathy). To determine the index term, a longlist of candidate terms and their rationale, was created using a literature review and interviews. This was shared with the community, to select their preferred terms (248 members (58%) including 149 (60%) surgeons, 45 (18%) other healthcare professionals and 54 (22%) People with DCM or their supporters) and finalized using a consensus meeting. To determine a definition, a medical definition framework was created using inductive thematic analysis of selected International Classification of Disease definitions. Separately, stakeholders submitted their suggested definition which also underwent inductive thematic analysis (317 members (76%), 190 (59%) surgeons, 62 (20%) other healthcare professionals and 72 (23%) persons living with DCM or their supporters). Using this definition framework, a working definition was created based on submitted content, and finalized using consensus meetings., Results: Degenerative Cervical Myelopathy was selected as the unifying term, defined in short, as a progressive spinal cord injury caused by narrowing of the cervical spinal canal., Conclusion: A consistent term and definition can support education and research initiatives. This was selected using a structured and iterative methodology, which may serve as an exemplar for others in the future., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Degenerative cervical myelopathy (DCM) arises from spinal degenerative changes injuring the cervical spinal cord. Most cord compression is incidental, referred to as asymptomatic spinal cord compression (ASCC). How and why ASCC differs from DCM is poorly understood. In this paper, we study a local cohort to identify specific types and groups of degenerative pathology more likely associated with DCM than ASCC., Methods: This study was a retrospective cohort analysis (IRB Approval ID: PRN10455). The frequency of degenerative findings between those with ASCC and DCM patients were compared using network analysis, hierarchical clustering, and comparison to existing literature to identify potential subgroups in a local cohort (N = 155) with MRI-defined cervical spinal cord compression. Quantitative measures of spinal cord compression (MSCC and MCC) were used to confirm their relevance., Results: ELF (8.7 %, 95 % CI 3.8-13.6 % vs 35.7 %, 95 % CI 27.4-44.0 %) Congenital Stenosis (3.9 %, 95 % CI 0.6-7.3 % vs 25.0 %, 95 % CI 17.5-32.5 %), and OPLL (0.0 %, 95 % CI 0.0-0.0 % vs 3.6 %, 95 % CI 0.3-6.8 %) were more likely in patients with DCM. Comparative network analysis indicated loss of lordosis was associated with ASCC, whilst ELF with DCM. Hierarchical Cluster Analysis indicated four sub-groups: multi-level disc disease with ELF, single-level disc disease without loss of lordosis and OPLL with DCM, and single-level disc disease with loss of lordosis with ASCC. Quantitative measures of cord compression were higher in groups associated with DCM, but similar in patients with single-level disc disease and loss of lordosis., Conclusions: This study identified four subgroups based on degenerative pathology requiring further investigation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this., Objective: The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes., Methods: Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders., Results: Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway., Conclusions: This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community., International Registered Report Identifier (irrid): DERR1-10.2196/46809., (©Irina Sangeorzan, Grazia Antonacci, Anne Martin, Ben Grodzinski, Carl M Zipser, Rory K J Murphy, Panoraia Andriopoulou, Chad E Cook, David B Anderson, James Guest, Julio C Furlan, Mark R N Kotter, Timothy F Boerger, Iwan Sadler, Elizabeth A Roberts, Helen Wood, Christine Fraser, Michael G Fehlings, Vishal Kumar, Josephine Jung, James Milligan, Aria Nouri, Allan R Martin, Tammy Blizzard, Luiz Roberto Vialle, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Anna MacDowall, Esther Martin-Moore, Martin Burwood, Lianne Wood, Abdul Lalkhen, Manabu Ito, Nicky Wilson, Caroline Treanor, Sheila Dugan, Benjamin M Davies. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.10.2023.)

Astrocytes are diverse brain cells that form large networks communicating via gap junctions and chemical transmitters. Despite recent advances, the functions of astrocytic networks in information processing in the brain are not fully understood. In culture, brain slices, and in vivo, astrocytes, and neurons grow in tight association, making it challenging to establish whether signals that spread within astrocytic networks communicate with neuronal groups at distant sites, or whether astrocytes solely respond to their local environments. A multi-electrode array (MEA)-based device called AstroMEA is designed to separate neuronal and astrocytic networks, thus allowing to study the transfer of chemical and/or electrical signals transmitted via astrocytic networks capable of changing neuronal electrical behavior. AstroMEA demonstrates that cortical astrocytic networks can induce a significant upregulation in the firing frequency of neurons in response to a theta-burst charge-balanced biphasic current stimulation (5 pulses of 100 Hz × 10 with 200 ms intervals, 2 s total duration) of a separate neuronal-astrocytic group in the absence of direct neuronal contact. This result corroborates the view of astrocytic networks as a parallel mechanism of signal transmission in the brain that is separate from the neuronal connectome. Translationally, it highlights the importance of astrocytic network protection as a treatment target., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Aim: Cervical Spondylotic Myelopathy (CSM) is a disabling condition arising from arthritic compression and consequent injury of the cervical spinal cord. Stratification of CSM severity has been useful to inform clinical practice and research analysis. In the UK the Myelopathy Disability Index (MDI) is a popular assessment tool and has been adopted by the British Spinal Registry. However, no categories of severity exist. Therefore, the aim of this study was to define categories of mild, moderate and severe., Method: An anchor-based analysis was carried out on previously collected data from a prospective observational cohort ( N  = 404) of patients with CSM scheduled for surgery and assessed pre-operatively and at 3, 12, 24 and 60 months post-operatively. Outcomes collected included the SF-36 version-1 quality of life measure, visual analogue scales for neck/arm/hand pain, MDI and Neck Disability Index (NDI). A Receiver Operating Curve (ROC) analysis, using the NDI for an anchor-based approach, was performed to identify MDI thresholds., Results: Complete data was available for 404 patients (219 Men, 185 Women). The majority of patients underwent anterior surgery (284, 70.3%). ROC curves plotted to identify the thresholds from mild to moderate to severe disease, selected optimal thresholds of 4-5 (AUC 0.83) and 8-9 (AUC 0.87). These MDI categories were validated against domains of the SF36 and VAS scores with expected positive linear correlations., Conclusion: Categories of mild, moderate and severe CSM according to the MDI of 4-5 and 8-9 were established based on the NDI.

Increasing evidence indicates that cellular identity can be reduced to the distinct gene regulatory networks controlled by transcription factors (TFs). However, redundancy exists in these states as different combinations of TFs can induce broadly similar cell types. We previously demonstrated that by overcoming gene silencing, it is possible to deterministically reprogram human pluripotent stem cells directly into cell types of various lineages. In the present study we leverage the consistency and precision of our approach to explore four different TF combinations encoding astrocyte identity, based on previously published reports. Analysis of the resulting induced astrocytes (iAs) demonstrated that all four cassettes generate cells with the typical morphology of in vitro astrocytes, which expressed astrocyte-specific markers. The transcriptional profiles of all four iAs clustered tightly together and displayed similarities with mature human astrocytes, although maturity levels differed between cells. Importantly, we found that the TF cassettes induced iAs with distinct differences with regards to their cytokine response and calcium signaling. In vivo transplantation of selected iAs into immunocompromised rat brains demonstrated long term stability and integration. In conclusion, all four TF combinations were able to induce stable astrocyte-like cells that were morphologically similar but showed subtle differences with respect to their transcriptome. These subtle differences translated into distinct differences with regards to cell function, that could be related to maturation state and/or regional identity of the resulting cells. This insight opens an opportunity to precision-engineer cells to meet functional requirements, for example, in the context of therapeutic cell transplantation., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)

Objectives: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM)., Design: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM., Participants and Setting: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation., Results: The survey was completed by 423 individuals from 68 different countries. A total of 22% of participants submitted research suggestions that were considered 'answered'. There was a significant difference between responses from different stakeholder groups (p<0.005). Spinal surgeons were the group which was most likely to submit an 'answered' research question. Respondents from South America were also most likely to submit 'answered' questions, when compared with other regions. However, there was no significant difference between responses from different stakeholder regions (p=0.4)., Conclusions: Knowledge translation challenges exist within DCM. This practical approach to measuring knowledge translation may offer a more responsive assessment to guide interventions, complementing existing metrics., Competing Interests: Competing interests: BD, JB, ODM, IS, ES, MGF and MRNK have voluntary roles at Myelopathy.org, an international DCM charity., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Degenerative cervical myelopathy (DCM) is a recently proposed umbrella term for symptomatic cervical spinal cord compression secondary to degeneration of the spine. Currently literature searching for DCM is challenged by the inconsistent uptake of the term 'DCM' with many overlapping keywords and numerous synonyms., Objectives: Here, we adapt our previous Ovid medline search filter for the Ovid embase database, to support comprehensive literature searching. Both embase and medline are recommended as a minimum for systematic reviews., Methods: References contained within embase identified in our prior study formed a 'development gold standard' reference database (N = 220). The search filter was adapted for embase and checked against the reference database. The filter was then validated against the 'validation gold standard'., Results: A direct translation was not possible, as medline indexing for DCM and the keywords search field were not available in embase. We also used the 'focus' function to improve precision. The resulting search filter has 100% sensitivity in testing., Discussion and Conclusion: We have developed a validated search filter capable of retrieving DCM references in embase with high sensitivity. In the absence of consistent terminology and indexing, this will support more efficient and robust evidence synthesis in the field., (© 2021 The Authors Health Information and Libraries Journal published by John Wiley & Sons Ltd on behalf of Health Libraries Group.)

Background: Degenerative cervical myelopathy (DCM) is a common and disabling neurodegenerative condition. Surgical decompression is the only evidence-based treatment to halt disease progression; however, diagnosis and access to timely treatment are often delayed, which contribute to significant disability and dependence. Supporting early diagnosis and access to timely treatment is a critical priority. Exploring these challenges, Myelopathy.org has observed that people with DCM may seek osteopathy care for their symptoms, both before and after diagnosis., Objective: This study aimed to describe the current interaction between osteopaths and people with DCM and understand how this may be targeted to enhance the DCM diagnostic pathway., Methods: Registered osteopaths in the United Kingdom completed a web-based survey hosted by the Institute of Osteopathy, as part of their institute's 2021 census. Responses were collected from February to May 2021. Demographic information about the respondents was captured, including age, gender, and ethnicity. Professional information captured included the year of qualification; region of practice; type of practice; and number of undiagnosed, operated diagnosed, and unoperated diagnosed DCM cases encountered per year. The completion of the survey was voluntary; however, a prize draw incentive was offered to participants., Results: The demographics were heterogenous for the 547 practitioners who completed the survey. There was representation from a wide range of demographic groups, including the level of experience, gender, age, and the region of United Kingdom. At least 68.9% (377/547) of osteopaths reported encounters with DCM each year. Osteopaths most frequently encountered patients with undiagnosed DCM, with a mean of 3 patient encounters per year. This compares to 2 encounters per year with patients with diagnosed DCM. The level of practitioner experience was positively correlated with the detection of undiagnosed DCM (P<.005). The influence of practitioner experience was corroborated by a subgroup analysis looking at the relationship between practitioner age on the detection of undiagnosed DCM. Osteopaths older than 54 years encountered an average of 4.2 cases per year, whereas those younger than 35 years detected 2.9 cases per year. Osteopaths in private clinics reported encounters with a greater mean number (4.4) of undiagnosed DCM cases per year than osteopaths in other clinic types (3.0)., Conclusions: Osteopaths reported that they frequently consult people with DCM, including those suspected to have undiagnosed or presurgical DCM. Given this concentrated presentation of early DCM and a workforce professionally trained to examine musculoskeletal disease, osteopaths could have an important role in accelerating access to timely treatment. We included a decision support tool and specialist referral template as a tool to support onward care., (©Jamie F M Brannigan, Oliver D Mowforth, Matthew Rogers, Helen Wood, Zahabiya Karimi, Mark R N Kotter, Benjamin M Davies. Originally published in JMIR Formative Research (https://formative.jmir.org), 09.05.2023.)

Study Design: Systematic review., Background: Although degenerative cervical myelopathy (DCM) is the most prevalent spinal cord condition worldwide, the pathophysiology remains poorly understood. Our objective was to evaluate existing histological findings of DCM on cadaveric human spinal cord tissue and explore their consistency with animal models., Methods: MEDLINE and Embase were systematically searched (CRD42021281462) for primary research reporting on histological findings of DCM in human cadaveric spinal cord tissue. Data was extracted using a piloted proforma. Risk of bias was assessed using Joanna Briggs Institute critical appraisal tools. Findings were compared to a systematic review of animal models (Ahkter et al. 2020 Front Neurosci 14)., Results: The search yielded 4127 unique records. After abstract and full-text screening, 19 were included in the final analysis, reporting on 150 autopsies (71% male) with an average age at death of 67.3 years. All findings were based on haematoxylin and eosin (H&E) staining. The most commonly reported grey matter findings included neuronal loss and cavity formation. The most commonly reported white matter finding was demyelination. Axon loss, gliosis, necrosis and Schwann cell proliferation were also reported. Findings were consistent amongst cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Cavitation was notably more prevalent in human autopsies compared to animal models., Conclusion: Few human spinal cord tissue studies have been performed. Neuronal loss, demyelination and cavitation were common findings. Investigating the biological basis of DCM is a critical research priority. Human spinal cord specimen may be an underutilised but complimentary approach., (© 2023. The Author(s).)

Purpose: Degenerative cervical myelopathy is a progressive slow-motion spinal cord injury. Surgery is the mainstay of treatment. Baseline disability predicts surgical recovery; therefore, timely treatment is critical to restoring function. However, current challenges mean most patients present with advanced disease and are instead left with life changing disabilities. While short-term mortality is rarely reported, the long-term effects of this on life expectancy are unknown, including whether function could be modifiable with timely treatment. This article investigates the effect of DCM on life expectancy., Methods: The survival of patients from an observational study of patients undergoing surgery from 1994 to 2007 was compared to their expected survival using a gender- and aged -matched cohort. Comparisons were made by one sample log-rank test and standardised mortality ratios. Factors associated with survival were explored using a Cox regression analysis, including disease severity., Results: A total of 357 patients were included in the analysis. After a median follow-up of 15.3 years, 135 of 349 patients had died; 114.7 deaths would have been expected. The DCM cohort had an increased risk of death compared to the non-DCM cohort (standardised mortality ratio 1.18 [95% CI: 1.02-1.34]. Age at operation 1.08 (95% CI: 1.07 to 1.1, p < 0.001) and severe DCM 1.6 (95% CI: 1.06 to 2.3, p = 0.02) were associated with worse survival (N = 287). In those surviving at least 2 years after surgery, only severe DCM was associated with conditional survival (HR 1.6, 95% CI 1.04 2.4, p = 0.03)., Conclusion: Life expectancy is reduced in those undergoing surgery for DCM. This is driven by premature mortality among those left with severe disability. As disability can be reduced with timely treatment, these findings reinforce the need for collective and global action to raise awareness of DCM and enable early diagnosis., (© 2023. The Author(s).)

Introduction: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for Health Research (NIHR) James Lind Alliance (JLA) Priority Setting Partnerships., Methods: Patient-generated word clouds were created for the four survey subsections of the AO Spine RECODE-DCM PSP: diagnosis, treatment, long-term management and other issues. These were then evaluated as a nested methodological study. Word-clouds were created and iteratively refined by an online support group of people with DCM, before being curated by the RECODE-DCM management committee and expert healthcare professional representatives. The final word clouds were embedded within the surveys administered at random to 50% of participants. DCM research uncertainties suggested by participants were compared pre- and post-word cloud presentation., Results: A total of 215 (50.9%) participants were randomised to the word cloud stream, including 118 (55%) spinal surgeons, 52 (24%) PwDCM and 45 (21%) oHCP. Participants submitted 434 additional uncertainties after word cloud review: word count was lower and more uniform across each survey subsections compared to pre-word cloud uncertainties. Twenty-three (32%) of the final 74 PSP summary questions did not have a post-word cloud contribution and no summary question was formed exclusively on post-word cloud uncertainties. There were differences in mapping of pre- and post-word cloud uncertainties to summary questions, with greater mapping of post-word cloud uncertainties to the number 1 research question priority: raising awareness. Five of the final summary questions were more likely to map to the research uncertainties suggested by participants after having reviewed the word clouds., Conclusions: Word clouds may increase the perspective of underrepresented stakeholders in the research question gathering stage of priority setting partnerships. This may help steer the process towards research questions that are of highest priority for people with the condition., (© 2023. The Author(s).)

Background: Degenerative 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., Methods: An 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., Results: All 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., Conclusions: A 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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CFM has declared that no competing interests exist. RY has declared that no competing interests exist. ZCM has declared that no competing interests exist. MGF currently serves as an academic editor at PLOS ONE. RRP has declared that no competing interests exist. JM has declared that no competing interests exist. KM has declared that no competing interests exist. MRNK has declared that no competing interests exist. BMD is supported by NIHR POLYFIX DCM and NIHR Clinical Doctoral Research Fellowship grants. BMD is a founder of MoveMed (a digital therapeutics platform which develops assessments and treatments using software). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Munro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The development of neural interfaces with superior biocompatibility and improved tissue integration is vital for treating and restoring neurological functions in the nervous system. A critical factor is to increase the resolution for mapping neuronal inputs onto implants. For this purpose, we have developed a new category of neural interface comprising induced pluripotent stem cell (iPSC)-derived myocytes as biological targets for peripheral nerve inputs that are grafted onto a flexible electrode arrays. We show long-term survival and functional integration of a biohybrid device carrying human iPSC-derived cells with the forearm nerve bundle of freely moving rats, following 4 weeks of implantation. By improving the tissue-electronics interface with an intermediate cell layer, we have demonstrated enhanced resolution and electrical recording in vivo as a first step toward restorative therapies using regenerative bioelectronics.

Introduction: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM., Methods and Analysis: RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care., Study Design: Clinical trial protocol V.2.2 October 2020., Ethics and Dissemination: Ethical approval has been obtained from HRA-Wales.The results will be presented at an international and national scientific conferences and in a peer-reviewed journals., Trial Registration Number: ISRCTN Number: ISRCTN16682024., Competing Interests: Competing interests: MRNK holds a research grant from clinical scientist award and has support for the study from Medicinova. MCP holds research grant award with the NIHR. BD holds research grants with NIHR HTA POLYFIX-DCM, Evelyn Trust (DCM-COINs) and award from National Lottary UK for developing a peer-to-peer support community for Degenerative Cervical myelopathy. BD is also a founder of MoveMed Ltd. PJH holds NIHR research grants., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Degenerative cervical myelopathy (DCM) is the most common cause of chronic, progressive spinal cord impairment worldwide. Patients experience substantial pain, functional neurological decline and disability. Health-related quality of life (HRQoL) appears to be particularly poor, even when compared to other chronic diseases. However, the determinants of HRQoL are poorly understood. The objective was to perform a systematic review of the determinants of quality of life of people with DCM., Methods: A systematic search was conducted in MEDLINE and Embase following PRISMA 2020 guidelines (PROSPERO CRD42018115675). Full-text papers in English, exclusively studying DCM, published before 26 March 2020 were eligible for inclusion and were assessed using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias 2 (RoB 2) tool. Study sample characteristics, patient demographics, cohort type, HRQoL instrument utilised, HRQoL score, and relationships of HRQoL with other variables were qualitatively synthesised., Results: A total of 1176 papers were identified; 77 papers and 13,572 patients were included in the final analysis. A total of 96% of papers studied surgical cohorts and 86% utilised the 36-Item Short Form Survey (SF-36) as a measure of HRQoL. HRQoL determinants were grouped into nine themes. The most common determinant to be assessed was surgical technique (38/77, 49%) and patient satisfaction and experience of pain (10/77, 13%). HRQoL appeared to improve after surgery. Pain was a negative predictor of HRQoL., Conclusion: Current data on the determinants of HRQoL in DCM are limited, contradictory and heterogeneous. Limitations of this systematic review include lack of distinction between DCM subtypes and heterogenous findings amongst the papers in which HRQoL is measured postoperatively or post-diagnosis. This highlights the need for greater standardisation in DCM research to allow further synthesis. Studies of greater precision are necessary to account for HRQoL being complex, multi-factorial and both time and context dependent.

Introduction: Degenerative cervical myelopathy (DCM) is a common and progressive neurological condition caused by injury of the cervical spinal cord by degenerative spinal pathology. Delayed diagnosis leading to avoidable and irreversible disability is a major current problem limiting patient outcomes. Lack of sufficient representation of DCM in undergraduate and postgraduate medical curricula may contribute to poor recognition of DCM by non-specialist doctors. The objective of this study was to assess the DCM teaching provision in UK medical schools and the DCM knowledge of UK medical students., Methods: UK medical students completed a web-based survey distributed nationally through university social media pages, university email bulletins and the national student network of Myelopathy.org. The survey comprised a 19-item questionnaire capturing data on student demographics, myelopathy teaching and myelopathy knowledge. Advertisements were repeated monthly over a 12-month recruitment period and participation was incentivised by entry into an Amazon voucher prize draw. Ethical approval for the study was granted by the Psychology Research Ethics Committee, University of Cambridge (PRE.2018.099)., Results: A total of 751 medical students from 32 British medical schools completed the survey. Medical students from all year groups participated. Most students (520; 72%) had not received any medical school teaching about DCM. When students had received DCM teaching, the duration of teaching was minimal (75% < 1 h). A total of 350 students (47%) reported conducting private study on DCM. Modal student self-rating of their own knowledge of DCM was ' terrible ' (356; 47%). There was no correlation between a student's subjective rating of their knowledge and their answers to objective questions. A total of 723 (96%) of students expressed interest in learning more about DCM, with lectures the preferred format., Conclusions: DCM appears to be a neglected condition in medical education which has implications for clinical practice. However, student enthusiasm to undertake private study suggests future teaching interventions will be well-received. Future work is necessary to characterise the format of DCM teaching that is most effective and to subsequently measure how educational interventions translate into clinical benefits.

Study Design: Cross-sectional internet survey of people living with degenerative cervical myelopathy., Objective: The purpose of this study was to quantify pain distribution, severity, and interference in persons with degenerative cervical myelopathy., Methods: Eighty-two participants with degenerative cervical myelopathy were recruited for this internet survey. This survey utilized the Michigan Body Map and brief pain inventory (BPI) to assess anatomical distribution and severity of pain as well as the patient derived modified Japanese Orthopedic Association scale (p-mJOA) for myelopathic severity and SF-36 for measures of health-related quality of life. Internal consistency was evaluated with Cronbach's alpha. Pearson's correlations were assessed with p-mJOA and SF-36. Multivariate analysis of variance was used to determine if history of prior surgery or concomitant pain diagnosis impacted experience of pain., Results: Michigan body map distribution and brief pain inventory severity and interference were correlated with p-mJOA and SF-36 scores (p < 0.05). Pain was moderate to severe in 78% of participants. Pain was commonly widespread. Pain scales were sufficiently internally consistent (α > 0.9). History of surgery or other pain diagnosis did not impact experience of pain in myelopathy., Conclusions: Pain is commonly identifiable in large areas of the body, is frequently moderate to severe in intensity and impacts quality of life and severity of myelopathy in a cohort of individuals with myelopathy who have pain.

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., (© 2022. The Author(s).)

Introduction: Progress in degenerative cervical myelopathy (DCM) is hindered by inconsistent measurement and reporting. This impedes data aggregation and outcome comparison across studies. This limitation can be reversed by developing a core measurement set (CMS) for DCM research. Previously, the AO Spine Research Objectives and Common Data Elements for DCM (AO Spine RECODE-DCM) defined 'what' should be measured in DCM: the next step of this initiative is to determine 'how' to measure these features. This protocol outlines the steps necessary for the development of a CMS for DCM research and audit., Methods and Analysis: The CMS will be developed in accordance with the guidance developed by the Core Outcome Measures in Effectiveness Trials and the Consensus-based Standards for the selection of health Measurement Instruments. The process involves five phases. In phase 1, the steering committee agreed on the constructs to be measured by sourcing consensus definitions from patients, professionals and the literature. In phases 2 and 3, systematic reviews were conducted to identify tools for each construct and aggregate their evidence. Constructs with and without tools were identified, and scoping reviews were conducted for constructs without tools. Evidence on measurement properties, as well as on timing of assessments, are currently being aggregated. These will be presented in phase 4: a consensus meeting where a multi-disciplinary panel of experts will select the instruments that will form the CMS. Following selection, guidance on the implementation of the CMS will be developed and disseminated (phase 5). A preliminary CMS review scheduled at 4 years from release., Ethics and Dissemination: Ethical approval was obtained from the University of Cambridge (HBREC2019.14). Dissemination strategies will include peer-reviewed scientific publications; conference presentations; podcasts; the identification of AO Spine RECODE-DCM ambassadors; and engagement with relevant journals, funders and the DCM community., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction worldwide. However, the current incidence of DCM is poorly understood. The Hospital Episode Statistics (HES) database contains details of all secondary care admissions across NHS hospitals in England. This study aimed to use HES data to characterise surgical activity for DCM in England., Methods: The HES database was interrogated for all cases of DCM between 2012 and 2019. DCM cases were identified from 5 ICD-10 codes. Age-stratified values were collected for 'Finished Consultant Episodes' (FCEs), which correspond to a patient's hospital admission under a lead clinician. Data was analysed to explore current annual activity and longitudinal change., Results: 34,903 FCEs with one or more of the five ICD-10 codes were identified, of which 18,733 (53.6%) were of working age (18-64 years). Mean incidence of DCM was 7.44 per 100,000 (SD ± 0.32). Overall incidence of DCM rose from 6.94 per 100,000 in 2012-2013 to 7.54 per 100,000 in 2018-2019. The highest incidence was seen in 2016-2017 (7.94 per 100,000). The median male number of FCEs per year (2919, IQR: 228) was consistently higher than the median female number of FCEs per year (2216, IQR: 326). The rates of both emergency admissions and planned admissions are rising., Conclusions: The incidence of hospitalisation for DCM in England is rising. Health care policymakers and providers must recognise the increasing burden of DCM and act to address both early diagnoses and access to treatment in future service provision plans., (© 2022. The Author(s).)

Degenerative cervical myelopathy (DCM) is a progressive cervical spinal cord injury brought about by mechanical stress from degenerative changes in the cervical spine. It is typically diagnosed on clinical symptoms and examination findings together with MRI findings. In this study, we explore the significance of these degenerative pathology to onset of DCM by performing the first meta-analysis on the prevalence of degenerative features reported on MRI amongst healthy and asymptomatic populations and compare this to the prevalence of degenerative features reported on MRI amongst a symptomatic population calculated in a previous review. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, cognizant of their adaptation for epidemiological studies. A search strategy was used to identify original research carrying out MRI screening of cervical spines of asymptomatic patients in MEDLINE and Embase from 1985 to present day. The search yielded a total of 1098 studies of which 17 were included in this meta-analysis covering a total of 5059 patients. Ossification of posterior longitudinal ligament (pooled asymptomatic prevalence of 0.4%, 95% Confidence Interval [0.1%, 0.8%]), enlargement of ligamentum flavum (pooled asymptomatic prevalence of 11.8%, 95% Confidence Interval [5.3%, 18.4%]) and degenerative multilevel disc pathology (pooled asymptomatic prevalence of 64.5%, 95% Confidence Interval [48.3%, 80.8%], I 2 100%) were found to be significantly lower in asymptomatic populations. Symptomatic populations have a prevalence of 10.5% (95% Confidence Interval [7.7%, 13.3%]) for ossification of posterior longitudinal ligament, 56.8% (95% Confidence Interval [52.3%, 61.3%]) for enlargement of ligamentum flavum and 89.7% (95% Confidence Interval [86.9%, 92.5%]) for degenerative multilevel disc pathology [18]. Understanding the natural history of DCM is a recognised research priority, and whilst these perspectives require further evaluation, they may be of significant relevance to the evolving biomechanical understanding of the disease., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Study Design: Cross-sectional survey., Objectives: Degenerative cervical myelopathy (DCM) is a common syndrome of acquired spinal cord impairment caused by canal stenosis secondary to arthritic changes of the spine. International guidelines consider physiotherapy an option for mild, stable DCM; however, few studies have been conducted on nonoperative management. The objective was to determine current usage and perceptions of nonoperative physiotherapy for DCM., Methods: Persons with DCM were recruited to a web-based survey. Participants with complete responses that had not received surgery were included (n = 167). Variables included symptom duration, treatment history, current disability, and demographic characteristics., Results: Disease and demographic characteristics were equivalent between those who did and did not receive physiotherapy. In all, 19.5% of physiotherapy recipients reported subjective benefit from physiotherapy. Those perceiving benefit had significantly higher mJOA (modified Japanese Orthopaedic Association) scores, lower neck pain scores, and shorter symptom duration. In multivariate logistic regression analysis, those with mild DCM were more likely to perceive benefit than those with severe DCM, as were those with moderate DCM (to a lesser extent). Individuals whose diagnosis was delayed 1 to 2 years were less likely to perceive benefit than those that waited 0 to 6 months., Conclusions: The provision of nonoperative physiotherapy in the management of DCM is inconsistent and appears to differ from international guidelines. Few patients perceived benefit from physiotherapy; however, this was more likely in those with mild DCM and in those with shorter symptom durations. Further work is needed to establish the appropriate role of physiotherapy for this population.

Study Design: Mixed-methods cross-sectional study., Objectives: Degenerative cervical myelopathy (DCM) is a common and disabling condition. While classically, assessment and diagnosis has focused on neuromuscular symptoms, many other disabilities have been linked. The aim of this study was to explore the consequences of DCM for those with lived experience, producing a long list to inform the development of a core outcome set for DCM research., Methods: A 2-stage process was used: a focus group session of people with DCM (PwCM) and their supporters (n = 8) discussed the impact of DCM. This was used to develop a preliminary list of consequences, which were then placed into a survey of an online community of DCM sufferers (n = 224). Survey participants were asked to tick the consequences that they had experienced and given the opportunity to submit additional. Additional consequences were reviewed by a group of healthcare professionals and PwCM and included if not already represented. Demographic information including disease severity, age, and sex were captured for sampling comparison., Results: A total of 52 outcomes were identified from the focus group and nominally divided into 2 categories; symptoms (36 outcomes) and handicaps (18 outcomes), and further evaluated using a survey. All outcomes were recognized by at least 5% of respondents. A further 16 outcomes were added following the survey., Conclusions: A list of DCM consequences has been defined from the perspective of PwCM. This will now be evaluated as part of AO Spine RECODE-DCM, an international multistakeholder collaboration to establish a core outcome set for research.

Study Design: Literature Review (Narrative)., Objective: To introduce the number one research priority for Degenerative Cervical Myelopathy (DCM): Raising Awareness., Methods: Raising awareness has been recognized by AO Spine RECODE-DCM as the number one research priority. This article reviews the evidence that awareness is low, the potential drivers, and why this must be addressed. Case studies of success from other diseases are also reviewed, drawing potential parallels and opportunities for DCM., Results: DCM may affect as many as 1 in 50 adults, yet few will receive a diagnosis and those that do will wait many years for it. This leads to poorer outcomes from surgery and greater disability. DCM is rarely featured in healthcare professional training programs and has received relatively little research funding (<2% of Amyotrophic Lateral Sclerosis or Multiple Sclerosis over the last 25 years). The transformation of stroke and acute coronary syndrome services, from a position of best supportive care with occasional surgery over 50 years ago, to avoidable disability today, represents transferable examples of success and potential opportunities for DCM. Central to this is raising awareness., Conclusion: Despite the devastating burden on the patient, recognition across research, clinical practice, and healthcare policy are limited. DCM represents a significant unmet need that must become an international public health priority.

Study Design: Survey., Introduction: AO Spine Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy (AO Spine RECODE-DCM) is an international initiative that aims to accelerate knowledge discovery and improve outcomes by developing a consensus framework for research. This includes defining the top research priorities, an index term and a minimum data set (core outcome set and core data elements set - core outcome set (COS)/core data elements (CDE))., Objective: To describe how perspectives were gathered and report the detailed sampling characteristics., Methods: A two-stage, electronic survey was used to gather and seek initial consensus. Perspectives were sought from spinal surgeons, other healthcare professionals and people with degenerative cervical myelopathy (DCM). Participants were allocated to one of two parallel streams: (1) priority setting or (2) minimum dataset. An email campaign was developed to advertise the survey to relevant global stakeholder individuals and organisations. People with DCM were recruited using the international DCM charity Myelopathy.org and its social media channels. A network of global partners was recruited to act as project ambassadors. Data from Google Analytics, MailChimp and Calibrum helped optimise survey dissemination., Results: Survey engagement was high amongst the three stakeholder groups: 208 people with DCM, 389 spinal surgeons and 157 other healthcare professionals. Individuals from 76 different countries participated; the United States, United Kingdom and Canada were the most common countries of participants., Conclusion: AO Spine RECODE-DCM recruited a diverse and sufficient number of participants for an international PSP and COS/CDE process. Whilst PSP and COS/CDE have been undertaken in other fields, to our knowledge, this is the first time they have been combined in one process.

Study Design: Narrative review., Objective: Degenerative cervical myelopathy is one of the most frequent impairments of the spinal cord encountered internationally in adults. Currently, surgical decompression is the recommended treatment for people with DCM (PwCM) presenting with moderate to severe symptoms or neurological deficits. However, despite surgical intervention, not all patients make a complete recovery due to the irreversible tissue damage within the spinal cord. The objective of this review is to describe the state and gaps in the current literature on rehabilitation for PwCM and possible innovative rehabilitation strategies., Methods: Literature search., Results: In other neurological disorders such as stroke and acute traumatic spinal cord injury (SCI), timely and strategic rehabilitation has been shown to be indispensable for maximizing functional outcomes, and it is imperative that appropriate perioperative rehabilitative interventions accompany surgical approaches in order to enable the best outcomes. In this review, the current state of knowledge regarding rehabilitation for PwCM is described. Additionally, various therapies that have shown to improve outcomes in comparable neurological conditions such as stroke and SCI which may be translated to DCM will be reviewed., Conclusions: We conclude that locomotor training and arm/hand therapy may benefit PwCM. Further, we conclude that body weight support, robotic assistance, and virtual/augmented reality therapies may be beneficial therapeutic analogs to locomotor and hand therapies.

Study Design: Overview of the methods used for a James Lind Alliance (JLA) Priority Setting Partnership (PSP)., Objectives: The objectives of this article are to (i) provide a brief overview of the JLA-facilitated PSP process; (ii) outline how research uncertainties were initially processed in the AO Spine RECODE-DCM PSP; and (iii) delineate the methods for interim prioritization and the priority setting workshop., Methods: A steering group was created to define the scope for the PSP, organize its activities, and establish protocols for decision-making. A survey was created asking what questions on the diagnosis, treatment, and long-term management of DCM should be answered by future research. Results from the survey were sorted into summary questions. Several databases were searched to identify literature that already answered these summary questions. The final list of summary questions was distributed by survey for interim prioritization. Participants were asked to select the top ten most important summary questions. The questions that were ranked the highest were discussed at an in-person consensus workshop., Results: The initial survey yielded a total of 3404 potential research questions. Of the in-scope submissions, 988 were related to diagnosis, 1324 to treatment, and 615 to long-term management of DCM. A total of 76 summary questions were developed to reflect the original submissions. Following a second survey, a list of the top 26 interim priorities was generated and discussed at the in-person priority setting workshop., Conclusions: PSPs enable research priorities to be identified that consider the perspectives and interests of all relevant stakeholders.

Study Design: Narrative review., Objectives: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM)., Methods: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM., Results: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals' risk for DCM development. Non-myelopathic spinal cord compression (NMSCC) is a common phenomenon with a prevalence of 24.2% in the healthy population, and 35.3% among individuals >60 years of age. Clinical radiculopathy and/or electrophysiological signs of cervical cord dysfunction appear to be risk factors for myelopathy development. Radiological progression of incidental Ossification of the Posterior Longitudinal Ligament (OPLL) is estimated at 18.3% over 81-months and development of myelopathy ranges between 0-61.5% (follow-up ranging from 40 to 124 months between studies) among studies. In patients with symptomatic DCM undergoing non-operative treatment, 20-62% will experience neurological deterioration within 3-6 years., Conclusion: Current estimates surrounding the natural history of DCM, particularly those individuals with mild or minimal impairment, lack precision. Clear predictors of clinical deterioration for those treated with non-operative care are yet to be identified. Future studies are needed on this topic to help improve treatment counseling and clinical prognostication.

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.

Study Design: Narrative review., Objectives: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process., Methods: Literature review summarising current evidence of establishing diagnostic criteria for DCM., Results: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. Therefore, making a prompt diagnosis of DCM in order to facilitate early surgical intervention is a clinical priority in DCM., Conclusion: There are often extensive delays in the diagnosis of DCM. Presently, no single set of diagnostic criteria exists for DCM, making it challenging for clinicians to make the diagnosis. Earlier diagnosis and subsequent specialist referral could lead to improved patient outcomes using existing treatment modalities.

Study Design: Narrative review., Objective: The current review aimed to describe the role of existing techniques and emerging methods of imaging and electrophysiology for the management of degenerative cervical myelopathy (DCM), a common and often progressive condition that causes spinal cord dysfunction and significant morbidity globally., Methods: A narrative review was conducted to summarize the existing literature and highlight future directions., Results: Anatomical magnetic resonance imaging (MRI) is well established in the literature as the key imaging tool to identify spinal cord compression, disc herniation/bulging, and inbuckling of the ligamentum flavum, thus facilitating surgical planning, while radiographs and computed tomography (CT) provide complimentary information. Electrophysiology techniques are primarily used to rule out competing diagnoses. However, signal change and measures of cord compression on conventional MRI have limited utility to characterize the degree of tissue injury, which may be helpful for diagnosis, prognostication, and repeated assessments to identify deterioration. Early translational studies of quantitative imaging and electrophysiology techniques show potential of these methods to more accurately reflect changes in spinal cord microstructure and function., Conclusion: Currently, clinical management of DCM relies heavily on anatomical MRI, with additional contributions from radiographs, CT, and electrophysiology. Novel quantitative assessments of microstructure, perfusion, and function have the potential to transform clinical practice, but require robust validation, automation, and standardization prior to uptake.

Study Design: Literature Review (Narrative)., Objective: To introduce the number 10 research priority for Degenerative Cervical Myelopathy: Individualizing Surgery., Methods: This article summarizes the current recommendations and indications for surgery, including how known prognostic factors such as injury time, age, disease severity, and associated comorbidities impact surgical outcome. It also considers key areas of uncertainty that should be the focus of future research., Results: While a small proportion of conservatively managed patients may remain stable, the majority will deteriorate over time. To date, surgical decompression is the mainstay of treatment, able to halt disease progression and improve neurologic function and quality of life for most patients. Whilst this recognition has led to recommendations on when to offer surgery, there remain many uncertainties including the type of surgery, or timing in milder and/or asymptomatic cases. Their clarification has the potential to transform outcomes, by ensuring surgery offers each individual its maximum benefit., Conclusion: Developing the evidence to better guide surgical decision-making at the individual patient level is a research priority for Degenerative Cervical Myelopathy.

Study Design: Literature Review (Narrative)., Objective: To contextualize AO Spine RECODE-DCM research priority number 5: What is the socio-economic impact of DCM? (The financial impact of living with DCM to the individual, their supporters, and society as a whole)., Methods: In this review, we introduce the methodology of health-economic investigation, including potential techniques and approaches. We summarize the current health-economic evidence within DCM, so far focused on surgical treatment. We also cover the first national estimate, in partnership with Myelopathy.org from the United Kingdom, of the cost of DCM to society. We then demonstrate the significance of this question to advancing care and outcomes in the field., Results: DCM is a common and often disabling condition, with a significant lack of recognition. While evidence demonstrates the cost-effectives of surgery, even among higher income countries, health inequalities exist. Further the prevalent residual disability in myelopathy, despite treatment affects both the individual and society as a whole. A report from the United Kingdom provides the first cost-estimate to their society; an annual cost of ∼£681.6 million per year, but this is likely a significant underestimate., Conclusion: A clear quantification of the impact of DCM is needed to raise the profile of a common and disabling condition. Current evidence suggests this is likely to be globally substantial.

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.

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.

Cell transplantation is an attractive treatment strategy for a variety of brain disorders, as it promises to replenish lost functions and rejuvenate the brain. In particular, transplantation of astrocytes has come into light recently as a therapy for amyotrophic lateral sclerosis (ALS); moreover, grafting of astrocytes also showed positive results in models of other conditions ranging from neurodegenerative diseases of older age to traumatic injury and stroke. Despite clear differences in etiology, disorders such as ALS, Parkinson's, Alzheimer's, and Huntington's diseases, as well as traumatic injury and stroke, converge on a number of underlying astrocytic abnormalities, which include inflammatory changes, mitochondrial damage, calcium signaling disturbance, hemichannel opening, and loss of glutamate transporters. In this review, we examine these convergent pathways leading to astrocyte dysfunction, and explore the existing evidence for a therapeutic potential of transplantation of healthy astrocytes in various models. Existing literature presents a wide variety of methods to generate astrocytes, or relevant precursor cells, for subsequent transplantation, while described outcomes of this type of treatment also differ between studies. We take technical differences between methodologies into account to understand the variability of therapeutic benefits, or lack thereof, at a deeper level. We conclude by discussing some key requirements of an astrocyte graft that would be most suitable for clinical applications.