Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

Idiopathic Fistula in an Unrepaired Submucous Cleft Palate.

Palatal fistulae are a recognised complication in individuals who have undergone surgical repair of a cleft palate, however, congenital or idiopathic palatal fistulae are rare. This report discusses the presentation and treatment of a 16-year-old female with a submucous cleft palate, who presented with a recent onset change in speech and evidence of a new palatal fistula. There was no history of recent infection or known trauma, and the patient had not undergone any previous palatal surgery. This report discusses the clinical presentation, recommended management and relevant literature for this rare phenomenon.

Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial.

BACKGROUND: Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation - commonly known as neuroma pain - and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP. METHODS: One hundred ten upper and lower limb amputees suffering from RLP will be recruited and assigned randomly to one of the surgical interventions (TMR, RPNI, or neuroma transposition) in an equal allocation ratio. Complete evaluations will be performed during a baseline period prior to the surgical intervention, and follow-ups will be conducted in short term (1, 3, 6, and 12 months post-surgery) and in long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participant is unsatisfied with the outcome of the treatment at that time, further treatment including one of the other procedures will be discussed in consultation with the clinical investigator at that site. DISCUSSION: A double-blind RCT is necessary for the establishment of evidence-based procedures, hence the motivation for this work. In addition, studies on pain are challenging due to the subjectivity of the experience and the lack of objective evaluation methods. Here, we mitigate this problem by including different pain evaluation methods known to have clinical relevance. We plan to analyse the primary variable, mean change in NRS (0-10) between baseline and the 12-month follow-up, using the intention-to-treat (ITT) approach to minimise bias and keep the advantage of randomisation. The secondary outcomes will be analysed on both ITT and per-protocol (PP). An adherence protocol (PP population) analysis will be used for estimating a more realistic effect of treatment. TRIAL REGISTRATION: ClincialTrials.gov NCT05009394.

Chronic Exertional Compartment Syndrome Requiring Bilateral Fasciotomy: An Atypical Complication of Familial Stiff Skin Syndrome in a Father and Son.

ABSTRACT: Stiff skin syndrome (SSS) is a rare cutaneous disorder characterized by cutaneous fibrosis resulting in the early onset of thickened and indurated skin, joint mobility restrictions, and contractures. We describe a father and son with familial SSS who presented with bilateral exertional pain and a confirmed diagnosis of chronic exertional compartment syndrome on 4-compartment pressure testing. Patients experienced restored functionality with bilateral 4-compartment fasciotomy. Chronic exertional compartment syndrome should be considered in the differential diagnosis of patients with SSS and chronic pain of the lower limbs.

Upper limb prostheses: bridging the sensory gap.

Replacing human hand function with prostheses goes far beyond only recreating muscle movement with feedforward motor control. Natural sensory feedback is pivotal for fine dexterous control and finding both engineering and surgical solutions to replace this complex biological function is imperative to achieve prosthetic hand function that matches the human hand. This review outlines the nature of the problems underlying sensory restitution, the engineering methods that attempt to address this deficit and the surgical techniques that have been developed to integrate advanced neural interfaces with biological systems. Currently, there is no single solution to restore sensory feedback. Rather, encouraging animal models and early human studies have demonstrated that some elements of sensation can be restored to improve prosthetic control. However, these techniques are limited to highly specialized institutions and much further work is required to reproduce the results achieved, with the goal of increasing availability of advanced closed loop prostheses that allow sensory feedback to inform more precise feedforward control movements and increase functionality.

Comparison of Patient Satisfaction on a Day-case Mastectomy Pathway for Breast Cancer Versus a Traditional Inpatient Delivery Model, Using a Validated Questionnaire.

BACKGROUND: In 2011, a guidance was issued by the National Health Service (NHS) Improvement a model on how mastectomy could be offered in the day-case setting. The goal of this guidance was to reduce inpatient bed days and cost to the NHS, and demonstrate that it can be performed within an acceptable safety profile. The aim of this study was to assess whether patients find the day-case pathway for mastectomy an acceptable management model. We compared complication rates between the day-case and inpatient delivery model. PATIENTS AND METHODS: This study was a retrospective analysis of patients' experience undergoing day-case (n=26) and inpatient mastectomy (n=60). The primary outcome measure was based on a telephone interview using a validated, standardised questionnaire. RESULTS: No statistically significant difference in the satisfaction levels between the two groups (raw scores 6.76 day-case vs. 6.15 inpatient, p=0.37) was demonstrated. We found no statistically significant difference between the two groups when specifically analysing whether patients found the first night harder as a day-case or inpatient (3.192 vs. 2.80, p=0.59, range 0-10). Our overall complications were 11.4% (day-case) and 18.3% (inpatients). Rates were comparable between the two groups and equivalent to published rates in the literature. CONCLUSION: There was no statistically significant difference in satisfaction scores between patients who had a mastectomy as an inpatient versus those who had their operation as a day-case procedure. In addition, there were no significant differences in the complication rates between the two groups. We conclude then that it is feasible and safe to offer day-case mastectomy, with no loss in patient satisfaction.

Outcomes, Challenges, and Pitfalls after Targeted Muscle Reinnervation in High-Level Amputees: Is It Worth the Effort?

BACKGROUND: Although the distal targets have been lost in proximal upper limb amputees, the neural signals for intuitive hand and arm function are still available and thus can be incorporated into more useful prosthetic function using targeted muscle reinnervation technique. In this article, the authors present their outcomes and range of indications in addition to experiences and pitfalls after 30 targeted muscle reinnervation cases at above-elbow and shoulder disarticulation level of amputation. METHODS: Thirty patients with above-elbow or shoulder disarticulation amputations were enrolled between 2012 and 2017. Indications for targeted muscle reinnervation surgery differed between improvement of prosthetic function (n = 19) and/or pain (n = 11). Functional outcome was evaluated with the Action Research Arm Test, the Southampton Hand Assessment Procedure, and the Clothespin-Relocation Test. Functional evaluation was performed at least at 6 months after final prosthetic fitting. RESULTS: All nerve transfers were successful and provided independent myoelectric signals. The 10 patients available for final functional evaluation showed Action Research Arm Test scores of 20.4 ± 1.9 and Southampton Hand Assessment Procedure scores of 40.5 ± 8.1. The Clothespin-Relocation Test showed a mean time of 34.3 ± 14.4 seconds. CONCLUSIONS: Targeted muscle reinnervation has improved prosthetic control and revolutionized neuroma treatment in upper limb amputees. Still, the rate of abandonment even after targeted muscle reinnervation surgery has been shown high, and several advances within the biotechnological interface will be needed to improve prosthetic function and acceptance in these patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Fascicular shifting: a novel technique to overcome large nerve defects.

OBJECTIVE Over the last decade, a number of authors have investigated the utility of different biological and synthetic matrices as alternatives to conventional nerve grafts. However, the autologous nerve graft remains the gold standard, even though it often involves using a pure sensory nerve to reconstruct a mixed or even a pure motor nerve. Furthermore, limited donor sites often necessitate a significant mismatch of needed nerve tissue, especially for large proximal nerve defects such as brachial plexus lesions. Here, the authors present a new technique that overcomes these problems: the fascicular shift procedure (FSP). A fascicular group of the nerve distal to the injury is harvested in a sufficient length to bridge the nerve defect. METHODS The method of fascicular shifting was tested at the sciatic nerve in 45 Lewis rats. In the experimental group, a 15-mm nerve defect was created and reconstructed with a fascicular group that was harvested directly distal to the gap. This group was compared with 1 negative control group (defect without reconstruction) and 3 positive control groups (sensory, motor, and mixed graft). After 12 weeks of nerve regeneration, outcome was evaluated using retrograde labeling, histomorphometric analysis, and muscle force analysis. RESULTS All reconstructed groups showed successful regeneration with various levels of function. The negative control group showed minimal force measurements that were of no functional value. The fascicular shift provided sufficient guidance to overcome nerve defects, had higher (p < 0.1) motor neuron counts (1958.75 ± 657.21) than the sensory graft (1263.50 ± 538.90), and was equal to motor grafts (1490.43 ± 794.80) and mixed grafts (1720.00 ± 866.421). This tendency of improved motor regeneration was confirmed in all analyses. The mixed graft group was compared with the experimental group to investigate the influence of the potential damage induced by the fascicular shift distal to the repair site. However, none of the analyses revealed an impairment of nerve regeneration for both the tibial and common peroneal index muscles. CONCLUSIONS This study demonstrates that harvesting a transplant from the nerve segment distal to the injury site offers a mixed graft without causing additional donor-site morbidity. These grafts perform statistically better than a standard sensory graft in terms of motor recovery. The fascicular shift presents a novel method to reconstruct large proximal nerve defects, making it immensely attractive in brachial plexus reconstruction.

Prosthesis Control with an Implantable Multichannel Wireless Electromyography System for High-Level Amputees: A Large-Animal Study.

BACKGROUND: Myoelectric prostheses lack a strong human-machine interface, leading to high abandonment rates in upper limb amputees. Implantable wireless electromyography systems improve control by recording signals directly from muscle, compared with surface electromyography. These devices do not exist for high amputation levels. In this article, the authors present an implantable wireless electromyography system for these scenarios tested in Merino sheep for 4 months. METHODS: In a pilot trial, the electrodes were implanted in the hind limbs of 24 Sprague-Dawley rats. After 8 or 12 weeks, impedance and histocompatibility were assessed. In the main trial, the system was tested in four Merino sheep for 4 months. Impedance of the electrodes was analyzed in two animals. Electromyographic data were analyzed in two freely moving animals repeatedly during forward and backward gait. RESULTS: Device implantation was successful in all 28 animals. Histologic evaluation showed a tight encapsulation after 8 weeks of 78.2 ± 26.5 µm subcutaneously and 92.9 ± 31.3 µm on the muscular side. Electromyographic recordings show a distinct activation pattern of the triceps, brachialis, and latissimus dorsi muscles, with a low signal-to-noise ratio, representing specific patterns of agonist and antagonist activation. Average electrode impedance decreased over the whole frequency range, indicating an improved electrode-tissue interface during the implantation. All measurements taken over the 4 months of observation used identical settings and showed similar recordings despite changing environmental factors. CONCLUSION: This study shows the implantation of this electromyography device as a promising alternative to surface electromyography, providing a potentially powerful wireless interface for high-level amputees.

Bionic reconstruction to restore hand function after brachial plexus injury: a case series of three patients.

BACKGROUND: Brachial plexus injuries can permanently impair hand function, yet present surgical reconstruction provides only poor results. Here, we present for the first time bionic reconstruction; a combined technique of selective nerve and muscle transfers, elective amputation, and prosthetic rehabilitation to regain hand function. METHODS: Between April 2011, and May 2014, three patients with global brachial plexus injury including lower root avulsions underwent bionic reconstruction. Treatment occurred in two stages; first, to identify and create useful electromyographic signals for prosthetic control, and second, to amputate the hand and replace it with a mechatronic prosthesis. Before amputation, the patients had a specifically tailored rehabilitation programme to enhance electromyographic signals and cognitive control of the prosthesis. Final prosthetic fitting was applied as early as 6 weeks after amputation. FINDINGS: Bionic reconstruction successfully enabled prosthetic hand use in all three patients. After 3 months, mean Action Research Arm Test score increased from 5·3 (SD 4·73) to 30·7 (14·0). Mean Southampton Hand Assessment Procedure score improved from 9·3 (SD 1·5) to 65·3 (SD 19·4). Mean Disabilities of Arm, Shoulder and Hand score improved from 46·5 (SD 18·7) to 11·7 (SD 8·42). INTERPRETATION: For patients with global brachial plexus injury with lower root avulsions, who have no alternative treatment, bionic reconstruction offers a means to restore hand function. FUNDING: Austrian Council for Research and Technology Development, Austrian Federal Ministry of Science, Research & Economy, and European Research Council Advanced Grant DEMOVE.

Multiregion thermal sensitivity mapping of the hand.

Previous neurophysiological studies of discrete hand regions have suggested the dorsum to be more sensitive to temperature changes than the palmar surface, but no multiple-region investigation of the corresponding dorsal and palmar regions has been performed. This study aimed to investigate whether the dorsum of the hand is more sensitive to temperature changes than the palm across multiple regions. In 15 healthy human volunteers, cold and warmth detection thresholds were measured in 10 defined areas of the hand using a thermode of 2.56 cm(2). The testing algorithm employed was the Method of Limits with a baseline temperature of 32 °C and a rate of change of 1°/s. In five subjects, cold-pain and heat-pain thresholds were also measured. All dorsal regions were significantly more sensitive to cold than equivalent palmar areas. Differences in warmth thresholds were not uniform but, overall, dorsal sensitivity was significantly higher. This study finds that the dorsal aspect of the hand was more sensitive to temperature changes than the palm, with higher sensitivity to painful thermal stimuli.