INTRODUCTION:Traumatic brachial plexus injuries (TBPI) are life-changing and can lead to permanent changes in function and pain within the arm and hand. Historically, TBPI research has reflected the priorities of researchers and clinicians rather than those with personal experience of living with a TBPI. The James Lind Alliance (JLA), supported by the National Institute for Health Research, has developed a rigorous methodology for increasing public engagement in research by giving an equal voice to patients, carers, and healthcare providers to ensure that their concerns are represented in future health research programmes. These projects are called priority setting partnerships (PSPs). METHODS:A JLA PSP, comprising patients, carers and clinicians, was created and completed to agree future research priorities in adult TBPI. The JLA PSP methodology was followed throughout. RESULTS:One-hundred and fifty-four respondents replied to an initial survey generating 704 questions. These were assessed, grouped and combined to create 68 summary questions or 'uncertainties'. Three were excluded after literature review suggested they had already been answered by research. Seventy-nine respondents answered an interim prioritization survey, choosing their top ten from the summary questions. In a workshop, nine patients, two carers and 11 clinicians met, discussed and ranked the top 22 questions from the interim survey to identify the top 10 research priorities. Psychology, physical therapy treatments and management pathways were among the top ranked priorities. CONCLUSION:These results will inform researchers and funding bodies about research priorities for patients, carers and clinicians to direct future research on TBPI. LEVEL OF EVIDENCE:V.

Each year, thousands of individuals, particularly young adults, experience traumatic brachial plexus injuries (TBPIs), leading to significant limitations, permanent disabilities, reduced quality of life, and infrequent return to work. Current treatments and assistive devices have shown limited success, resulting in considerable social and economic challenges for patients. Given the devastating nature of this injury and the lack of literature on return to work rates among young adults, this study aims to determine the percentage of individuals reintegrating into work after a TBPI. Furthermore, it compares outcomes across different health care systems, including those in Germany, Serbia, and the United Kingdom. This dual approach has been selected to investigate the influence of various factors on the outcomes associated with returning to work after TBPI. Preliminary findings indicate that approximately 60% of patients with TBPI return to work, although most require a change in their occupational roles. Despite variations in health care systems and governmental support, the reintegration of patients with TBPI into work and society remains a critical and universal challenge. This comparative analysis highlights disparities in TBPI research and outcomes, providing valuable insights for future improvements in patient care and support mechanisms.

A 73-year-old woman was referred to a National Centre for Peripheral Nerve Injury with a post-operative left radial nerve degenerative lesion following open reduction and internal fixation of a proximal third humerus fracture using radiolucent Arthrex FiberTape® Cerclage as an adjunct to plating to improve stability. Intra-operative photographs illustrate compression of the radial nerve under the cerclage construct. Use of radiolucent cerclage for humerus fractures is increasing with modern systems capable of withstanding an ultimate load of 4300 N. We highlight the risk of debilitating neurological injury when not deployed safely and describe anatomical high-risk zones for injury. We emphasize the impact of delay in diagnosis and treatment.

Nerve grafting, tendon transfer and joint fusion are routinely used to improve the upper limb function in patients with brachial plexus palsies. Newer techniques have been developed that provide additional options for reconstruction. Nerve transfer is a tool for restoring upper limb function in total root avulsions where nerve grafting is not possible. In partial brachial plexus injuries, nerve transfers can greatly improve shoulder, elbow, wrist and hand function. Intraoperative electrical stimulation can be used to diagnose precisely which nerve is injured and to choose which nerve fascicles should be transferred. Finally, measuring the postoperative outcome can improve the evaluation of our techniques. The aim of this article was to present the current techniques used to treat patients with brachial plexus injury.

IntroductionRegional anaesthesia provides important clinical benefits to patients but is underutilised. A barrier to widespread adoption may be the focus of regional anaesthesia research on novel techniques rather than evaluating and optimising existing approaches. Research priorities in regional anaesthesia identified by anaesthetists have been published, but the views of patients, carers and other healthcare professionals have not been considered previously. Therefore, we launched a multidisciplinary research priority setting partnership that aimed to establish key regional anaesthesia research priorities for the UK.MethodsResearch suggestions from key stakeholders (defined by their interaction with regional anaesthesia) were gathered using an online survey. These suggestions were analysed to identify common themes and then combined to formulate indicative research questions. After an extensive literature review, unanswered and partially answered questions were prioritised via an interim online survey and then ranked as a top 10 list during a final live virtual multidisciplinary prioritisation workshop.ResultsIn total, 210 individuals completed the initial survey and suggested 518 research questions. Fifty-seven indicative questions were formed, of which three were considered fully answered after literature review and one not feasible. The interim online survey received 335 responses, which identified the 24 highest priority questions from the 53 presented. At the final live prioritisation workshop, through a nominal group process, we identified the top 10 regional anaesthesia research priorities. These aligned with three broad thematic areas: pain management (two questions); patient safety (six questions); and recovery from surgery (two questions).DiscussionThis initiative has resulted in a list of research questions prioritised by patients, carers and a multidisciplinary group of healthcare professionals that should be used to inform and support future regional anaesthesia research in the UK.

BackgroundPeripheral nerve injuries are burdensome on healthcare systems, individuals and society as a whole. The current standard of treatment for neurotmesis is primary neurorrhaphy or nerve grafting. However, several patients do not recover their full function. There has been a suggestion that primary distal neurolysis at common entrapment sites maximises surgical outcomes; however, no guidelines exist on this practice. This scoping review aims to ascertain the existing evidence on prophylactic distal decompression of peripheral nerves following repair.MethodsA literature search was performed using Ovid Medline, PubMed, Embase and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews for studies published in the past 50 years. Studies were screened using a selection criteria and study quality was assessed using standardised tools. Furthermore, thematic content analysis was performed.ResultsSix studies were eligible for inclusion after screening; all studies were retrospective and at most level 3 evidence. No studies were designed specifically to assess the efficacy of distal neurolysis following proximal repair, thus no comparative data with control cohorts are available. All studies that recommended distal decompression of proximally repaired nerves based their conclusions on cases observed by the authors in practice or from theories on nerve regeneration.ConclusionsThis systematic review suggests that the evidence on the role of immediate distal neurolysis in primary neurorrhaphy is inadequate. Recommendations are limited by the lack of large-scale and generalisable data. Further research is needed with definitive objective outcomes and patient-related outcome measures.

Background Double fascicular nerve transfer (DFT) is often performed to re-animate the elbow flexors. Studies of motor recovery following this surgery have exclusively reported on the objective outcome of muscle power. Questionnaire studies allow researchers and clinicians to learn from patients and better direct care towards their needs. To date, no research has focused on self-assessed recovery following DFT for elbow flexion. Methods This observational cross-sectional study aimed to give an account of patient-assessed outcomes following DFT. The bespoke questionnaire included: (a) self-reported strength and (b) the Stanmore percentage of normal elbow assessment. Results Sixty-two patients participated in the study. Participants were grouped according to time post-surgery. Statistical analysis confirmed that data were comparable between groups ( p=0.10). Self-assessed strength Median scores were 0.5 kg <2 years post-surgery, 3 kg at 2 to 5 years, 2 kg at 5 to 8 years and 1.3 kg in the >8 years group. Stanmore Percentage of Normal Elbow Assessment Mean scores (%) were 35 (SD ± 25) <2 years, 56 (SD ± 31) at 2 to 5 years, 44 (SD ± 25) at 5 to 8 years and 46 (SD ± 29) >8 years groups. Conclusions This is the first study of self-assessed recovery following DFT. Scores peaked around 4 years post-operation. Future research should focus on the long-term self-reported outcome of nerve transfer surgery.

Optimal functional recovery following peripheral nerve injuries (PNIs) is dependent upon early recognition and prompt referral to specialist centres for appropriate surgical intervention. Technologies which facilitate the early detection of PNI would allow faster referral rates and encourage improvements in patient outcomes. Serum Neurofilament light chain (NfL) measurements are cheaper to perform, easier to access and interpret than many conventional methods used for nerve injury diagnosis, such as electromyography and/or magnetic resonance imaging assessments, but changes in serum NfL levels following traumatic PNI have not been investigated. This pre‐clinical study aimed to determine whether serum NfL levels can: (1) detect the presence of a nerve trauma and (2) delineate between different severities of nerve trauma.

Background:Qualitative studies following Brachial Plexus Injury (BPI) suggest that return to employment has a major influence on life satisfaction and psychological well-being. However, few studies have focused on return to work following BPI. The physical strain and intensity of an occupation may influence the ability of an individual to return to employment. This study aimed to provide information about the impact of workload intensity on employment status following BPI. Methods:This is an observational, retrospective study of 74 participants who responded to a postal questionnaire, sharing information regarding their employment status pre- and post-BPI. The reported occupations were assessed for workload intensity and assigned a Reichsausschuss für Arbeitszeitermittlung (REFA) classification by two assessors. Results:Forty-one out of 74 participants (57%) had to change their employment following their BPI. Changes in occupation were more likely if the pre-injury REFA score was 3 or 4 (n = 22). In the Complete plexus injury group (n = 8), 100% changed occupation. In the Partial plexus injury group (n = 66) 50% changed occupation. Hand dominance had no significant influence on change of employment (p = 0.37). Conclusion:This study is the first to focus on the impact of BPI on employment status and workload intensity. Just over half the participants did not maintain the same employment following their BPI and one in five became unemployed. Future research should review the factors that contribute to the inability to return to work. This may direct enhancements in rehabilitation provision and enable healthcare services to focus on facilitating individuals back to the workplace.

Aim: To investigate co-contraction in reinnervated elbow flexor muscles following a nerve transfer. Materials & methods: 12 brachial plexus injury patients who received a nerve transfer to reanimate elbow flexion were included in this study. Surface electromyography (EMG) recordings were used to quantify co-contraction during sustained and repeated isometric contractions of reinnervated and contralateral uninjured elbow flexor muscles. Reuslts: For the first time, this study reveals reinnervated muscles demonstrated a trend toward higher co-contraction ratios when compared with uninjured muscle and this is correlated with an earlier onset of muscle fatigability. Conclusion: Measurements of co-contraction should be considered within muscular function assessments to help drive improvements in motor recovery therapies.

This article explores the extent to which the emergence of networked conceptions of etiology and network-oriented approaches to the organization of medical practice were historically congruent. Focusing on interwar malariology, it contextualizes the development of ecological approaches to infection management and control in terms of mosquito-borne malariotherapeutic practice. In Britain, mosquito breeding programs directed toward the therapeutic infection of mental hospital patients prompted malariologists to modify and refine existing environmental approaches to malaria. Breeding mosquitoes, attending to patients, and maintaining sources of malarial blood modified malariologists' etiological presumptions, contributing to a wider breakdown of associations between race, place, and disease. Simultaneously, the emergence of an international network of malariotherapy-devoted institutions helped transform malariological practice. Examination of a collaboration between British and Romanian malariologists shows one way in which this network contributed to the transformation of malariology from a formal League of Nations-focused endeavor to one distributed along common lines of research and prevention.

Muscle spindles are sensory organs that detect and mediate both static and dynamic muscle stretch and monitor muscle position, through a specialised cell population, termed intrafusal fibres. It is these fibres that provide a key contribution to proprioception and muscle spindle dysfunction is associated with multiple neuromuscular diseases, aging and nerve injuries. To date, there are few publications focussed on de novo generation and characterisation of intrafusal muscle fibres in vitro. To this end, current models of skeletal muscle focus on extrafusal fibres and lack an appreciation for the afferent functions of the muscle spindle. The goal of this study was to produce and define intrafusal bag and chain myotubes from differentiated C2C12 myoblasts, utilising the addition of the developmentally associated protein, Neuregulin 1 (Nrg-1). Intrafusal bag myotubes have a fusiform shape and were assigned using statistical morphological parameters. The model was further validated using immunofluorescent microscopy and western blot analysis, directed against an extensive list of putative intrafusal specific markers, as identified in vivo. The addition of Nrg-1 treatment resulted in a 5-fold increase in intrafusal bag myotubes (as assessed by morphology) and increased protein and gene expression of the intrafusal specific transcription factor, Egr3. Surprisingly, Nrg-1 treated myotubes had significantly reduced gene and protein expression of many intrafusal specific markers and showed no specificity towards intrafusal bag morphology. Another novel finding highlights a proliferative effect for Nrg-1 during the serum starvation-initiated differentiation phase, leading to increased nuclei counts, paired with less myotube area per myonuclei. Therefore, despite no clear collective evidence for specific intrafusal development, Nrg-1 treated myotubes share two inherent characteristics of intrafusal fibres, which contain increased satellite cell numbers and smaller myonuclear domains compared with their extrafusal neighbours. This research represents a minimalistic, monocellular C2C12 model for progression towards de novo intrafusal skeletal muscle generation, with the most extensive characterisation to date. Integration of intrafusal myotubes, characteristic of native, in vivo intrafusal skeletal muscle into future biomimetic tissue engineered models could provide platforms for developmental or disease state studies, pre-clinical screening, or clinical applications.

The hope of translational medicine is to identify treatments that improve the rate and quality of neuronal recovery following peripheral nerve injuries (PNI). A major obstacle to the trial of new treatments for PNI is the absence of sensitive and responsive measures of clinical function, which are the ultimate outcome of the biological events of nerve regeneration.The development of objective clinical measures of nerve regeneration that are sensitive, responsive, and valid is challenging for a number of reasons. The Peripheral Nervous System (PNS) allows us to have complex interactions with our surroundings (for example, the perception of pain, touch, and temperature). Developing objective measures that reflect the multimodal function of the PNS and separate it from psychological influences on that experience is difficult. Secondly, the recovery of function following PNI is dependent upon a number of biological processes at multiple levels including the end organ, the damaged nerve segments, as well as the Central Nervous System (CNS). Clinical measures that quantify these changes and relate them to the recovery of function are not well documented.The biological process of neural regeneration is often assessed in the research arena through postmortem tissue assessment. However, the harvesting of vital nerve tissue for assessment of neural regeneration often risks the function that has been recovered. Therefore, this is not feasible when studying the biological process of regeneration in humans. This has necessitated the development of noninvasive methods to attain the same degree of assessment of biological regeneration.In order to assess the biological mechanisms of tissue and cellular regeneration, the relationship of these processes with human clinical experiences needs to be explained. Correlating these new areas of human assessment will help establish the influence of the complex biological processes that underpin nerve regeneration on the lived experience of nerve injury.This chapter provides an overview of the clinical, neurophysiological, and imaging assessments that can provide pre-, intra-, and postoperative measures of nerve regeneration. This will inform the development of outcome measures that have the capacity to detect a meaningful cinical response in clinical trials which aim to detemine the efficacy of new therapies for PNI.

>Peripheral nerve injuries(PNI) are common following blunt or penetrating trauma and can lead to disability and chronic pain in affected individuals, with limited options available to promote regeneration and functional recovery.From animal models, it is known that the regenerative capacity of the peripheral nervous system(PNS) is heavily dependent upon the remarkable ability of Schwann cells to undergo a phenotypic shift from a supportive/

The development of outcome measures that can track the recovery of reinnervated muscle would benefit the clinical investigation of new therapies which hope to enhance peripheral nerve repair. The primary objective of this study was to assess the validity of volumetric Magnetic Resonance Imaging (MRI) as an outcome measure of muscle reinnervation by testing its reproducibility, responsiveness and relationship with clinical indices of muscular function. Over a 3-year period 25 patients who underwent nerve transfer to reinnervate elbow flexor muscles were assessed using intramuscular electromyography (EMG) and MRI (median post-operative assessment time of 258 days, ranging from 86 days pre-operatively to 1698 days post- operatively). Muscle power (Medical Research Council (MRC) grade) and Stanmore Percentage of Normal Elbow Assessment (SPONEA) assessment was also recorded for all patients. Sub-analysis of peak volitional force (PVF), muscular fatigue and co-contraction was performed in those patients with MRC > 3. The responsiveness of each parameter was compared using Pearson or Spearman correlation. A Hierarchical Gaussian Process (HGP) was implemented to determine the ability of volumetric MRI measurements to predict the recovery of muscular function. Reinnervated muscle volume per unit Body Mass Index (BMI) demonstrated good responsiveness (R-2 = 0.73, p < 0.001). Using the temporal and muscle volume per unit BMI data, a HGP model was able to predict MRC grade and SPONEA with a mean absolute error (MAE) of 0.73 and 1.7 respectively. Muscle volume per unit BMI demonstrated moderate to good positive correlations with patient reported impairments of reinnervated muscle; co- contraction (R-2 = 0.63, p = 0.02) and muscle fatigue (R-2 = 0.64, p = 0.04). In summary, volumetric MRI analysis of reinnervated muscle is highly reproducible, responsive to post-operative time and demonstrates correlation with clinical indices of muscle function. This encourages the view that volumetric MRI is a promising outcome measure for muscle reinnervation which will drive advancements in motor recovery therapy.

Abstract Introduction Improved outcome measures of muscle reinnervation would facilitate clinical translation of new therapies which hope to enhance human peripheral nerve repair. Valid outcome measures should be receptive to the biological process of muscle reinnervation and correlate with clinical assessments of muscular function. This study investigated the responsiveness of volumetric MRI to the biological process of muscle reinnervation and its relationship with clinical indices of muscular function. Method Twenty-five patients who underwent nerve transfer to reinnervate elbow flexor muscles were followed-up at a median time of 258 days (-86 to 1698 days) post-operatively for a mean of two (one to three) volumetric MRI assessments. Medical Research Council (MRC) grade, peak volitional force (PVF), muscular fatigue, co-contraction and Stanmore Percentage of Normal Elbow Assessment (SPONEA) was also measured at each appointment. The responsiveness of each parameter was compared using Pearson or Spearman correlation as appropriate. Results Elbow flexor muscle volume per unit BMI demonstrated responsiveness to the biological process of muscle reinnervation (R2=0.73, p < 0.001) and correlated with patient reported impairments of reinnervated muscle; co-contraction (R2=0.63, p = 0.02) and muscle fatigue (R2=0.64, p = 0.04). Conclusions Volumetric MRI may is an excellent candidate as an outcome measure of muscle reinnervation.