Autonomic nerve fibers aberrantly reinnervate denervated facial muscles and alter muscle fiber population.

The surgical redirection of efferent neural input to a denervated muscle via a nerve transfer can reestablish neuromuscular control after nerve injuries. The role of autonomic nerve fibers during the process of muscular reinnervation remains largely unknown. Here, we investigated the neurobiological mechanisms behind the spontaneous functional recovery of denervated facial muscles in male rodents. Recovered facial muscles demonstrated an abundance of cholinergic axonal endings establishing functional neuromuscular junctions. The parasympathetic source of the neuronal input was confirmed to be in the pterygopalatine ganglion. Furthermore, the autonomically reinnervated facial muscles underwent a muscle fiber change to a purely intermediate muscle fiber population (MHCIIa). Finally, electrophysiological tests revealed that the postganglionic parasympathetic fibers travel to the facial muscles via the sensory infraorbital nerve. Our findings demonstrated expanded neuromuscular plasticity of denervated striated muscles enabling functional recovery via alien autonomic fibers. These findings may further explain the underlying mechanisms of sensory protection implemented to prevent atrophy of a denervated muscle.SIGNIFICANCE STATEMENT:Nerve injuries represent significant morbidity and disability for patients. Rewiring motor nerve fibers to other target muscles have shown to be a successful approach in the restoration of motor function. This demonstrates the remarkable capacity of the central nervous system to adapt to the needs of the neuromuscular system. Yet, the capability of skeletal muscles being reinnervated by non-motor axons remains largely unknown. Here, we show that under deprivation of original efferent input, the neuromuscular system can undergo functional and morphological remodeling via autonomic nerve fibers. This may explain neurobiological mechanisms of the sensory protection phenomenon, which is due to parasympathetic reinnervation.

Spinal cord from body donors is suitable for multicolor immunofluorescence.

Immunohistochemistry is a powerful tool for studying neuronal tissue from humans at the molecular level. Obtaining fresh neuronal tissue from human organ donors is difficult and sometimes impossible. In anatomical body donations, neuronal tissue is dedicated to research purposes and because of its easier availability, it may be an alternative source for research. In this study, we harvested spinal cord from a single organ donor 2 h (h) postmortem and spinal cord from body donors 24, 48, and 72 h postmortem and tested how long after death, valid multi-color immunofluorescence or horseradish peroxidase (HRP) immunohistochemistry is possible. We used general and specific neuronal markers and glial markers for immunolabeling experiments. Here we showed that it is possible to visualize molecularly different neuronal elements with high precision in the body donor spinal cord 24 h postmortem and the quality of the image data was comparable to those from the fresh organ donor spinal cord. High-contrast multicolor images of the 24-h spinal cords allowed accurate automated quantification of different neuronal elements in the same sample. Although there was antibody-specific signal reduction over postmortem intervals, the signal quality for most antibodies was acceptable at 48 h but no longer at 72 h postmortem. In conclusion, our study has defined a postmortem time window of more than 24 h during which valid immunohistochemical information can be obtained from the body donor spinal cord. Due to the easier availability, neuronal tissue from body donors is an alternative source for basic and clinical research.

Feasibility of a Wireless Implantable Multi-electrode System for High-bandwidth Prosthetic Interfacing: Animal and Cadaver Study.

BACKGROUND: Currently used prosthetic solutions in upper extremity amputation have limited functionality, owing to low information transfer rates of neuromuscular interfacing. Although surgical innovations have expanded the functional potential of the residual limb, available interfaces are inefficacious in translating this potential into improved prosthetic control. There is currently no implantable solution for functional interfacing in extremity amputation which offers long-term stability, high information transfer rates, and is applicable for all levels of limb loss. In this study, we presented a novel neuromuscular implant, the the Myoelectric Implantable Recording Array (MIRA). To our knowledge, it is the first fully implantable system for prosthetic interfacing with a large channel count, comprising 32 intramuscular electrodes. QUESTIONS/PURPOSES: The purpose of this study was to evaluate the MIRA in terms of biocompatibility, functionality, and feasibility of implantation to lay the foundations for clinical application. This was achieved through small- and large-animal studies as well as test surgeries in a human cadaver. METHODS: We evaluated the biocompatibility of the system's intramuscular electromyography (EMG) leads in a rabbit model. Ten leads as well as 10 pieces of a biologically inert control material were implanted into the paravertebral muscles of four animals. After a 3-month implantation, tissue samples were taken and histopathological assessment performed. The probes were scored according to a protocol for the assessment of the foreign body response, with primary endpoints being inflammation score, tissue response score, and capsule thickness in µm. In a second study, chronic functionality of the full system was evaluated in large animals. The MIRA was implanted into the shoulder region of six dogs and three sheep, with intramuscular leads distributed across agonist and antagonist muscles of shoulder flexion. During the observation period, regular EMG measurements were performed. The implants were removed after 5 to 6 months except for one animal, which retained the implant for prolonged observation. Primary endpoints of the large-animal study were mechanical stability, telemetric capability, and EMG signal quality. A final study involved the development of test surgeries in a fresh human cadaver, with the goal to determine feasibility to implant relevant target muscles for prosthetic control at all levels of major upper limb amputation. RESULTS: Evaluation of the foreign body reaction revealed favorable biocompatibility and a low-grade tissue response in the rabbit study. No differences regarding inflammation score (EMG 4.60 ± 0.97 [95% CI 4.00 to 5.20] versus control 4.20 ± 1.48 [95% CI 3.29 to 5.11]; p = 0.51), tissue response score (EMG 4.00 ± 0.82 [95% CI 3.49 to 4.51] versus control 4.00 ± 0.94 [95% CI 3.42 to 4.58]; p > 0.99), or thickness of capsule (EMG 19.00 ± 8.76 µm [95% CI 13.57 to 24.43] versus control 29.00 ± 23.31 µm [95% CI 14.55 to 43.45]; p = 0.29) were found compared with the inert control article (high-density polyethylene) after 3 months of intramuscular implantation. Throughout long-term implantation of the MIRA in large animals, telemetric communication remained unrestricted in all specimens. Further, the implants retained the ability to record and transmit intramuscular EMG data in all animals except for two sheep where the implants became dislocated shortly after implantation. Electrode impedances remained stable and below 5 kΩ. Regarding EMG signal quality, there was little crosstalk between muscles and overall average signal-to-noise ratio was 22.2 ± 6.2 dB. During the test surgeries, we found that it was possible to implant the MIRA at all major amputation levels of the upper limb in a human cadaver (the transradial, transhumeral, and glenohumeral levels). For each level, it was possible to place the central unit in a biomechanically stable environment to provide unhindered telemetry, while reaching the relevant target muscles for prosthetic control. At only the glenohumeral level, it was not possible to reach the teres major and latissimus dorsi muscles, which would require longer lead lengths. CONCLUSION: As assessed in a combination of animal model and cadaver research, the MIRA shows promise for clinical research in patients with limb amputation, where it may be employed for all levels of major upper limb amputation to provide long-term stable intramuscular EMG transmission. CLINICAL RELEVANCE: In our study, the MIRA provided high-bandwidth prosthetic interfacing through intramuscular electrode sites. Its high number of individual EMG channels may be combined with signal decoding algorithms for accessing spinal motor neuron activity after targeted muscle reinnervation, thus providing numerous degrees of freedom. Together with recent innovations in amputation surgery, the MIRA might enable improved control approaches for upper limb amputees, particularly for patients with above-elbow amputation where the mismatch between available control signals and necessary degrees of freedom for prosthetic control is highest.

Rehabilitation of high upper limb amputees after Targeted Muscle Reinnervation.

STUDY DESIGN: This is a Delphi study based on a scoping literature review. INTRODUCTION: Targeted muscle reinnervation (TMR) enables patients with high upper limb amputations to intuitively control a prosthetic arm with up to six independent control signals. Although there is a broad agreement regarding the importance of structured motor learning and prosthetic training after such nerve transfers, to date, no evidence-based protocol for rehabilitation after TMR exists. PURPOSE OF THE STUDY: We aimed at developing a structured rehabilitation protocol after TMR surgery after major upper limb amputation. The purpose of the protocol is to guide clinicians through the full rehabilitation process, from presurgical patient education to functional prosthetic training. METHODS: European clinicians and researchers working in upper limb prosthetic rehabilitation were invited to contribute to a web-based Delphi study. Within the first round, clinical experts were presented a summary of recent literature and were asked to describe the rehabilitation steps based on their own experience and scientific evidence. The second round was used to refine these steps, while the importance of each step was rated within the third round. RESULTS: Experts agreed on a rehabilitation protocol that consists of 16 steps and starts before surgery. It is based on two overarching principles, namely the necessity of multiprofessional teamwork and a careful selection and education of patients within the rehabilitation team. Among the different steps in therapy, experts rated the training with electromyographic biofeedback as the most important one. DISCUSSION: Within this study, a first rehabilitation protocol for TMR patients based on a broad experts' consensus and relevant literature could be developed. The detailed steps for rehabilitation start well before surgery and prosthetic fitting, and include relatively novel interventions as motor imagery and biofeedback. Future studies need to further investigate the clinical outcomes and thereby improve therapists' practice. CONCLUSION: Graded rehabilitation offered by a multiprofessional team is needed to enable individuals with upper limb amputations and TMR to fully benefit from prosthetic reconstruction. LEVEL OF EVIDENCE: Low.

[Surgical management of peripheral nerves after extremity loss]. / Der chirurgische Umgang mit peripheren Nerven nach Extremitätenverlust.

BACKGROUND: After limb loss, it is the surgeon's task to provide the patient with a pain-free and resilient residual limb. Particularly in the upper extremity, there is an additional functional aspect, as appropriate muscle signals are needed to control myoelectric prostheses. Surgical management of peripheral nerves within the residual limb plays a central role both in terms of pain treatment as well as functional human-machine interfacing. OBJECTIVES: The presentation of current surgical procedures for dealing with peripheral nerves after limb amputation. MATERIAL AND METHODS: A literature search is carried out regarding the surgical prophylaxis and therapy of neuroma and phantom limb pain, as well as techniques to improve the functional interface between residual limb and prosthesis. Practical recommendations are formulated based on relevant literature, as well as the experiences of the authors. RESULTS AND CONCLUSIONS: There is a large number of different surgical techniques, particularly for the management of painful neuromas. Of the conventional methods, intramuscular implantation of the terminal nerves is commonly used with good results. Newer techniques such as targeted muscle reinnervation (TMR) and the regenerative peripheral nerve interface (RPNI) aim for the first time to provide functional end organs to the nerve even after amputation. In addition to the improved control of myoelectric prostheses, these methods further show excellent results for treatment and prevention of neuroma and phantom limb pain.

Neuralgic amyotrophy: a paradigm shift in diagnosis and treatment.

Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome, is characterised by sudden pain attacks, followed by patchy muscle paresis in the upper extremity. Recent reports have shown that incidence is much higher than previously assumed and that the majority of patients never achieve full recovery. Traditionally, the diagnosis was mainly based on clinical observations and treatment options were confined to application of corticosteroids and symptomatic management, without proven positive effects on long-term outcomes. These views, however, have been challenged in the last years. Improved imaging methods in MRI and high-resolution ultrasound have led to the identification of structural peripheral nerve pathologies in NA, most notably hourglass-like constrictions. These pathognomonic findings have paved the way for more accurate diagnosis through high-resolution imaging. Furthermore, surgery has shown to improve clinical outcomes in such cases, indicating the viability of peripheral nerve surgery as a valuable treatment option in NA. In this review, we present an update on the current knowledge on this disease, including pathophysiology and clinical presentation, moving on to diagnostic and treatment paradigms with a focus on recent radiological findings and surgical reports. Finally, we present a surgical treatment algorithm to support clinical decision making, with the aim to encourage translation into day-to-day practice.

[The role of the reconstructive surgeon treating neuropathic pain after iatrogenic nerve lesions]. / Die Rolle der rekonstruktiven Chirurgie bei neuropathischen Schmerzen.

The role of the reconstructive surgeon treating neuropathic pain after iatrogenic nerve lesions Abstract. Any surgical intervention bears the potential risk of iatrogenic nerve lesions with consecutive functional deficits and chronic neuropathic pain syndromes. These complications obviously result in patient dissatisfaction and frequently bear legal consequences. A broad experience in diagnosis and treatment of peripheral nerve lesions is needed to initiate the proper diagnostics and treatment modalities in an according time frame. The quick and appropriate response after any nerve trauma is an important criterion for success or failure of the reconstruction. Surgeons from other specialities, who do not deal with nerve lesions in their daily routine, need a distinct overview about diagnostics and treatment, to initiate the adequate therapy shortly after the injury. This review provides an overview of peripheral nerve lesions, the underlying pathomechanisms, the diagnosis and reconstructive treatment options. Even with highest accuracy and experience, nerve lesions are part of any surgical practice. However, we are convinced that with adequate and prompt action of the primary surgeon a good patient-doctor relationship may be maintained, often more favourable results may be achieved after reconstruction and legal trials avoided.

Bionic hand as artificial organ: Current status and future perspectives.

Even though the hand comprises only 1% of our body weight, about 30% of our central nervous systems (CNS) capacity is related to its control. The loss of a hand thus presents not only the loss of the most important tool allowing us to interact with our environment, but also leaves a dramatic sensory-motor deficit that challenges our CNS. Reconstruction of hand function is therefore not only an essential part of restoring body integrity and functional wholeness but also closes the loop of our neural circuits diminishing phantom sensation and neural pain. If biology fails to restore meaningful function, today we can resort to complex mechatronic replacement that have functional capabilities that in some respects even outperform biological alternatives, such as hand transplantation. As with replantation and transplantations, the challenge of bionic replacement is connecting the target with the CNS to achieve natural and intuitive control. In recent years, we have developed a number of strategies to improve neural interfacing, signal extraction, interpretation and stable mechanical attachment that are important parts of our current research. This work gives an overview of recent advances in bionic reconstruction, surgical refinements over technological interfacing, skeletal fixation, and modern rehabilitation tools that allow quick integration of prosthetic replacement.

Predicting wrist kinematics from motor unit discharge timings for the control of active prostheses.

BACKGROUND: Current myoelectric control algorithms for active prostheses map time- and frequency-domain features of the interference EMG signal into prosthesis commands. With this approach, only a fraction of the available information content of the EMG is used and the resulting control fails to satisfy the majority of users. In this study, we predict joint angles of the three degrees of freedom of the wrist from motor unit discharge timings identified by decomposition of high-density surface EMG. METHODS: We recorded wrist kinematics and high-density surface EMG signals from six able-bodied individuals and one patient with limb deficiency while they performed movements of three degrees of freedom of the wrist at three different speeds. We compared the performance of linear regression to predict the observed individual wrist joint angles from, either traditional time domain features of the interference EMG or from motor unit discharge timings (which we termed neural features) obtained by EMG decomposition. In addition, we propose and test a simple model-based dimensionality reduction, based on the physiological notion that the discharge timings of motor units are partly correlated. RESULTS: The regression approach using neural features outperformed regression on classic global EMG features (average R2 for neural features 0.77 and 0.64, for able-bodied subjects and patients, respectively; for time-domain features 0.70 and 0.52). CONCLUSIONS: These results indicate that the use of neural information extracted from EMG decomposition can advance man-machine interfacing for prosthesis control.

Axonal components of nerves innervating the human arm.

OBJECTIVE: Axons traveling within the brachial plexus are responsible for the dexterous control of human arm and hand movements. Despite comprehensive knowledge on the topographical anatomy of nerves innervating the human upper limbs, the definite quantity of sensory and motor axons within this neural network remains elusive. Our aim was to perform a quantitative analysis of the axonal components of human upper limb nerves based on highly specific molecular features from spinal cord level to the terminal nerves at wrist level. METHODS: Nerve specimen harvest at predefined harvesting sites (plexus roots and cords as well as major nerves originating from the brachial plexus innervating the arm and hand) was performed in 9 human heart-beating organ donors. Double immunofluorescence staining using antibodies against choline-acetyltransferase and neurofilament was performed to differentiate motor and sensory axons on nerve cross sections. RESULTS: Three hundred fifty thousand axons emerge from the spinal cord to innervate the human upper limb, of which 10% are motor neurons. In all nerves studied, sensory axons outnumber motor axons by a ratio of at least 9:1. The sensory axon contribution increases when moving distally, whereas only 1,700 motor axons reach the hand to innervate the intrinsic musculature. INTERPRETATION: Our results suggest that upper limb motor execution, and particularly dexterous coordination of hand movement, require an unexpectedly low number of motor neurons, with a large convergence of afferent input for feedback control. Ann Neurol 2017;82:396-408.

Home-Based Tactile Discrimination Training Reduces Phantom Limb Pain.

BACKGROUND: Phantom limb pain (PLP) affects a high percentage of amputees. Since treatment options are limited, low quality of life and addiction to pain medication frequently occur. New treatments, such as mirror therapy or electrical sensory discrimination training, make use of the brain's plasticity to alleviate this centrally derived pain. AIM: This pilot study assessed the question of whether home-based tactile discrimination training (TDT) leads to a stronger decrease in PLP levels compared to standard massage treatment. DESIGN: Controlled study. SETTING: Outpatient. POPULATION: Amputees (upper/lower extremity) with a PLP score of 4 or higher out of a possible 10 points on the visual analog scale. METHODS: Eight patients participated in the study. The treatment phase comprised 2 weeks (15 minutes daily). Subjects were examined at baseline, after treatment, 2 weeks after completing treatment, and 4 weeks after completing treatment. Pain was assessed using the West Haven-Yale Multidimensional Pain Inventory. RESULTS: There was a significantly stronger reduction in PLP in the treatment group receiving TDT. PLP intensity ratings were significantly reduced at the end of therapy, and at 2 and 4 weeks after completing treatment compared to pretreatment. CONCLUSIONS: TDT seems to be an easy, cheap, time-effective, and safe method to achieve sustained alleviation of PLP and also brings about a positive change in body image. REHABILITATION IMPACT: Home-based TDT could achieve a sustained reduction in PLP and should be considered as a possible alternative to established treatment methods.

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.

Automated muscle fiber type population analysis with ImageJ of whole rat muscles using rapid myosin heavy chain immunohistochemistry.

INTRODUCTION: Skeletal muscle consists of different fiber types which adapt to exercise, aging, disease, or trauma. Here we present a protocol for fast staining, automatic acquisition, and quantification of fiber populations with ImageJ. METHODS: Biceps and lumbrical muscles were harvested from Sprague-Dawley rats. Quadruple immunohistochemical staining was performed on single sections using antibodies against myosin heavy chains and secondary fluorescent antibodies. Slides were scanned automatically with a slide scanner. Manual and automatic analyses were performed and compared statistically. RESULTS: The protocol provided rapid and reliable staining for automated image acquisition. Analyses between manual and automatic data indicated Pearson correlation coefficients for biceps of 0.645-0.841 and 0.564-0.673 for lumbrical muscles. Relative fiber populations were accurate to a degree of ± 4%. CONCLUSIONS: This protocol provides a reliable tool for quantification of muscle fiber populations. Using freely available software, it decreases the required time to analyze whole muscle sections. Muscle Nerve 54: 292-299, 2016.

Diffusion tensor tractography for the surgical management of peripheral nerve sheath tumors.

OBJECT Peripheral nerve sheath tumors (PNSTs) are uncommon but bear a significant risk of malignancy. High-resolution MRI is the standard technique for characterizing PNSTs. However, planning the appropriate extent of resection and subsequent reconstructive strategies is highly dependent on the intraoperative findings because preoperative MRI evaluation can be insufficient. Diffusion tensor tractography (DTT) represents a recently developed advanced MRI technique that reveals the microstructure of tissues based on monitoring the random movement of water molecules. DTT has the potential to provide diagnostic insights beyond conventional MRI techniques due to its mapping of specific fibrillar nerve structures. Here, DTT was applied to evaluate PNSTs and to examine the usefulness of this method for the correct delineation of tumor and healthy nerve tissue and the value of this information in the preoperative planning of surgical interventions. METHODS In this prospective study, patients with the clinical symptoms of a PNST were investigated using DTT 3-Tesla MRI scans. Image data processing and tractography were performed using the FACT (fiber assessment by continuous tracking) algorithm and multiple-regions-of-interest approach. The surgical findings were then compared with the results of the DTT MRI scans. Preoperative fascicle visualization and the correlation with the intraoperative findings were graded. RESULTS In a 21-month period, 12 patients with PNSTs were investigated (7 female and 5 male patients with a mean age of 46.2 ± 19.2 years). All patients underwent surgical removal of the tumor. Schwannoma was the most common benign histopathological finding (n = 7), whereas 2 malignant lesions were detected. In 10 of 12 patients, good preoperative nerve fascicle visualization was achieved using DTT scans. In 9 of 10 patients with good preoperative fascicle visualization, good intraoperative correlation between the DTT scans and surgical anatomy was found. CONCLUSIONS DTT properly visualizes the peripheral nerve fascicles and their correct anatomical relation to PNST. DTT represents a promising new method for the preinterventional planning of nerve tumor resection.

Targeted muscle reinnervation in bionic upper limb reconstruction: current status and future directions.

Selective nerve transfers are used in the setting of upper limb amputation to improve myoelectric prosthesis control. This surgical concept is referred to as targeted muscle reinnervation (TMR) and describes the rerouting of the major nerves of the arm onto the motor branches of the residual limb musculature. Aside from providing additional myosignals for prosthetic control, TMR can treat and prevent neuroma pain and possibly also phantom limb pain. This article reviews the history and current applications of TMR in upper limb amputation, with a focus on practical considerations. It further explores and identifies technological innovations to improve the man-machine interface in amputation care, particularly regarding implantable interfaces, such as muscle electrodes and osseointegration. Finally, future clinical directions and possible scientific avenues in this field are presented and critically discussed.

Excitation of natural spinal reflex loops in the sensory-motor control of hand prostheses.

Sensory feedback for prosthesis control is typically based on encoding sensory information in specific types of sensory stimuli that the users interpret to adjust the control of the prosthesis. However, in physiological conditions, the afferent feedback received from peripheral nerves is not only processed consciously but also modulates spinal reflex loops that contribute to the neural information driving muscles. Spinal pathways are relevant for sensory-motor integration, but they are commonly not leveraged for prosthesis control. We propose an approach to improve sensory-motor integration for prosthesis control based on modulating the excitability of spinal circuits through the vibration of tendons in a closed loop with muscle activity. We measured muscle signals in healthy participants and amputees during different motor tasks, and we closed the loop by applying vibration on tendons connected to the muscles, which modulated the excitability of motor neurons. The control signals to the prosthesis were thus the combination of voluntary control and additional spinal reflex inputs induced by tendon vibration. Results showed that closed-loop tendon vibration was able to modulate the neural drive to the muscles. When closed-loop tendon vibration was used, participants could achieve similar or better control performance in interfaces using muscle activation than without stimulation. Stimulation could even improve prosthetic grasping in amputees. Overall, our results indicate that closed-loop tendon vibration can integrate spinal reflex pathways in the myocontrol system and open the possibility of incorporating natural feedback loops in prosthesis control.

Emerging Value of Osseointegration for Intuitive Prosthetic Control after Transhumeral Amputations: A Systematic Review.

Background: Upper extremity limb loss profoundly impacts a patient's quality of life and well-being and carries a significant societal cost. Although osseointegration allows the attachment of the prosthesis directly to the bone, it is a relatively recent development as an alternative to conventional socket prostheses. The objective of this review was to identify reports on osseointegrated prosthetic embodiment for transhumeral amputations and assess the implant systems used, postoperative outcomes, and complications. Methods: A systematic review following PRISMA and AMSTAR guidelines assessed functional outcomes, implant longevity and retention, activities of daily living, and complications associated with osseointegrated prostheses in transhumeral amputees. Results: The literature search yielded 794 articles, with eight of these articles (retrospective analyses and case series) meeting the inclusion criteria. Myoelectric systems equipped with Osseointegrated Prostheses for the Rehabilitation of Amputees implants have been commonly used as transhumeral osseointegration systems. The transhumeral osseointegrated prostheses offered considerable improvements in functional outcomes, with participants demonstrating enhanced range of motion and improved performance of activities compared with traditional socket-based prostheses. One study demonstrated the advantage of an osseointegrated implant as a bidirectional gateway for signal transmission, enabling intuitive control of a bionic hand. Conclusions: Osseointegrated prostheses hold the potential to significantly improve the quality of life for individuals with transhumeral amputations. Continued research and clinical expansion are expected to lead to the realization of enhanced efficacy and safety in this technique, accompanied by cost reductions over time as a result of improved efficiencies and advancements in device design.

Peripheral neural interfaces: Skeletal muscles are hyper-reinnervated according to the axonal capacity of the surgically rewired nerves.

Advances in robotics have outpaced the capabilities of man-machine interfaces to decipher and transfer neural information to and from prosthetic devices. We emulated clinical scenarios where high- (facial) or low-neural capacity (ulnar) donor nerves were surgically rewired to the sternomastoid muscle, which is controlled by a very small number of motor axons. Using retrograde tracing and electrophysiological assessments, we observed a nearly 15-fold functional hyper-reinnervation of the muscle after high-capacity nerve transfer, demonstrating its capability of generating a multifold of neuromuscular junctions. Moreover, the surgically redirected axons influenced the muscle's physiological characteristics, by altering the expression of myosin heavy-chain types in alignment with the donor nerve. These findings highlight the remarkable capacity of skeletal muscles to act as biological amplifiers of neural information from the spinal cord for governing bionic prostheses, with the potential of expressing high-dimensional neural function for high-information transfer interfaces.