Search

OBJECTIVE Intrinsic function is indispensable for dexterous hand movements. Distal ulnar nerve defects can result in intrinsic muscle dysfunction and sensory deficits. Although the ulnar nerve’s fascicular anatomy has been extensively studied, quantitative and topographic data on motor axons traveling within this nerve remain elusive. METHODS The ulnar nerves of 14 heart-beating organ donors were evaluated. The motor branches to the flexor carpi ulnaris (FCU) and flexor digitorum profundus (FDP) muscles and the dorsal branch (DoBUN) as well as 3 segments of the ulnar nerve were harvested in 2-cm increments. Samples were subjected to double immunofluorescence staining using antibodies against choline acetyltransferase and neurofilament. RESULTS Samples revealed more than 25,000 axons in the ulnar nerve at the forearm level, with a motor axon proportion of only 5%. The superficial and DoBUN showed high axon numbers of more than 21,000 and 9300, respectively. The axonal mapping of more than 1300 motor axons revealed an increasing motor/sensory ratio from the proximal ulnar nerve (1:20) to the deep branch of the ulnar nerve (1:7). The motor branches (FDP and FCU) showed that sensory axons outnumber motor axons by a ratio of 10:1. CONCLUSIONS Knowledge of the detailed axonal architecture of the motor and sensory components of the human ulnar nerve is of the utmost importance for surgeons considering fascicular grafting or nerve transfer surgery. The low number of efferent axons in motor branches of the ulnar nerve and their distinct topographical distribution along the distal course of the nerve is indispensable information for modern nerve surgery.

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.

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 myosin heavy chain type IIa. 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 STATEMENTNerve injuries represent significant morbidity and disability for patients. Rewiring motor nerve fibers to other target muscles has shown to be a successful approach in the restoration of motor function. This demonstrates the remarkable capacity of the CNS to adapt to the needs of the neuromuscular system. Yet, the capability of skeletal muscles being reinnervated by nonmotor axons remains largely unknown. Here, we show that under deprivation of original efferent input, the neuromuscular system can undergo functional and morphologic remodeling via autonomic nerve fibers. This may explain neurobiological mechanisms of the sensory protection phenomenon, which is because of parasympathetic reinnervation.

The authors report the case of a forty-year old man with an inveterate ulnar nerve neuroma following a laceration injury of his left wrist twenty-three years ago. He presented with a typical ulnar claw-hand deformity and debilitating neuropathic pain in his hand (VAS 8.4). Pre-operative imaging revealed a neuroma of the ulnar nerve at the Guyon’s canal. Moreover, a complete atrophy of all intrinsic hand muscles innervated by the ulnar nerve was present. A Zancolli lasso procedure was performed to reduce the clawing effect. The neuroma was resected producing a nerve defect of five centimeters. Since the injury dated back more than two decades and any motor recovery was deemed impossible at that point, the motor fascicle of the ulnar nerve, i.e. the deep branch, was harvested and used as an autologous nerve graft to bridge the defect. The deep branch fascicle was dissected proximally, harvested and shifted into the defect to be coapted with the superficial branch fascicle in an end-to-end fashion. The presented procedure resulted in satisfying and sustained pain reduction (VAS 2.5) at two-year follow-up. Hence, the authors recommend considering fascicular shift procedure in peripheral sensory nerve reconstruction as a cost-effective alternative.

Zusammenfassung Operationsziel Ziel dieser Operation ist eine frühzeitige Innervation der intrinsischen Handmuskulatur durch Fasern des N. medianus, um einer irreversiblen Atrophie des Muskelgewebes vorzubeugen. Der Nerventransfer erfolgt mittels Babysitter-Interponat, welches jeweils End-zu-Seit an Spender- und Empfängernerv koaptiert wird. Der Eingriff wird kombiniert mit einer proximalen Rekonstruktion des N. ulnaris. Indikationen Hochgradige Läsionen des N. ulnaris ohne spontane Regeneration, insbesondere bei proximaler Läsionshöhe und/oder später Patientenvorstellung. Kontraindikationen Irreversible Denervation der intrinsischen Muskulatur; Schwäche oder Ausfall des R. thenaris. Operationstechnik Der Zugang erfolgt über dem beugeseitigen Handgelenk durch eine longitudinale Inzision. Der R. profundus des N. ulnaris sowie der R. thenaris des N. medianus werden nach Spalten des Retinaculum flexorum dargestellt. Es erfolgt eine Verbindung der beiden Nerven über ein autologes Interponat, welches jeweils in End-zu-Seit-Manier über ein epineurales Fenster an den Spender- (R. thenaris) und den Empfängernerv (R. profundus) koaptiert wird. Dies ermöglicht die zeitgerechte Regeneration einiger motorischer Medianusaxone in die intrinsische Muskulatur, um einer irreversiblen Degeneration vorzubeugen. Aufgrund der End-zu-Seit-Nervennaht wird der Schaden des Spendernervs auf ein Minimum reduziert. Durch die gleichzeitig durchgeführte Rekonstruktion des N. ulnaris auf Höhe der Läsion wird im späteren Verlauf auch eine autochthone Reinnervation der intrinsischen Muskulatur ermöglicht. Weiterbehandlung Postoperativ werden Laschen eingebracht und ein steriler Handverband angelegt. Erster Verbandswechsel und Zug der Laschen am ersten postoperativen Tag, Nahtentfernung in der Regel nach 2 Wochen. Bereits nach 1 Woche kann die ergotherapeutische Beübung zum Erhalt der Gelenkbeweglichkeit erfolgen. Nach den ersten Zeichen der motorischen und/oder sensiblen Reinnervation erfolgt eine zielgerichtete Physiotherapie zum Wiedererlernen der alltäglichen Handfunktion. Ergebnisse Diese Technik wurde bisher an 3 Patienten mit hochgradiger Läsion des N. ulnaris vorgestellt. Bei einer Follow-up-Zeit von 6 Jahren konnten alle Patienten Muskelkraft von ≥ M3 erlangen, mit allgemein gutem bis exzellentem Ergebnis anhand der modifizierten Bishop Rating Scale.

Immunohistochemistry is a powerful tool to study neuronal tissue from humans at the molecular level. To obtain 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 the easier availability, it may be an alternative source for research. In the present study, we harvested spinal cord from a single organ donor 2 hours (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 as well as glial markers to visualize different neurons. Here we showed that it is possible to visualize molecularly different neuronal elements with high precision in the body donor spinal cord 24h postmortem and the quality of the image data was comparable to those from the fresh organ donor spinal cord. High contrast multicolor images of 24h 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 was acceptable for most antibodies at 48h but no longer at 72h postmortem. In conclusion, our study has defined a postmortem time window of more than 24h during which valid immunohistochemical information can be obtained from body donor spinal cord. Due to the easier availability, neuronal tissue from body donors is an alternative source for basic and clinical research.

Negative expectations regarding nerve reconstruction in the elderly prevail in the literature, but little is known about the effectiveness of nerve transfers in patients with brachial plexus injuries aged over 60 years. We present a series of five patients (1 female, 4 male) aged between 60 and 81 years (median 62.0 years) who underwent nerve reconstruction using multiple nerve transfers in brachial plexopathies. The etiology of brachial plexus injury was trauma (n = 2), or iatrogenic, secondary to spinal surgical laminectomy, tumor excision and radiation for breast cancer (n = 3). All but one patient underwent a one-stage reconstruction including neurolysis and extra-anatomical nerve transfer alone (n = 2) or combined with anatomical reconstruction by sural nerve grafts (n = 2). One patient underwent a two-stage reconstruction, which involved a first stage anatomical brachial plexus reconstruction followed by a second stage nerve transfer. Neurotizations were performed as double (n = 3), triple (n = 1) or quadruple (n = 1) nerve or fascicular transfers. Overall, at least one year postoperatively, successful results, characterized by a muscle strength of M3 or more, were restored in all cases, two patients even achieving M4 grading in the elbow flexion. This patient series challenges the widely held dogma that brachial plexus reconstruction in older patients will produce poor outcomes. Distal nerve transfers are advantageous as they shorten the reinnervation distance. Healthy, more elderly patients should be judiciously offered the whole spectrum of reconstructive methods and postoperative rehabilitation concepts to regain useful arm and hand function and thus preserve independence after a traumatic or nontraumatic brachial plexus injury.

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.The presentation of current surgical procedures for dealing with peripheral nerves after limb amputation.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.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.HINTERGRUND: Nach Verlust einer Gliedmaße ist es die Aufgabe des Chirurgen, einen möglichst schmerzfreien und belastbaren Stumpf zu formen. Hierbei kommt insbesondere an der oberen Extremität ein funktioneller Aspekt hinzu, da zur Steuerung myoelektrischer Prothesen entsprechende Muskelsignale notwendig sind. Der Umgang mit peripheren Nerven im Stumpfbereich nimmt sowohl hinsichtlich der Schmerztherapie als auch der funktionellen Mensch-Maschinen-Anbindung eine zentrale Rolle ein.Die Darstellung aktueller chirurgischer Verfahren zum Umgang mit peripheren Nerven nach Extremitätenamputation.Es erfolgt eine Literaturrecherche bzgl. chirurgischer Prophylaxe und Therapie von Neurom- und Phantomschmerzen, sowie zu Techniken zur Verbesserung der funktionellen Schnittstelle zwischen Stumpf und Prothese. Anhand relevanter Arbeiten sowie der Erfahrungen der Autoren werden entsprechende Empfehlungen formuliert.Es gibt eine große Anzahl an verschiedenen Operationstechniken, insbesondere im Umgang mit schmerzhaften Neuromen. Von den klassischen Verfahren findet besonders häufig die intramuskuläre Verlagerung der endständiger Nerven Anwendung. Neuere Techniken wie Targeted Muscle Reinnervation (TMR) und Regenerative Peripheral Nerve Interface (RPNI) zielen erstmals darauf ab, dem Nerven auch nach Amputation funktionelle Endorgane zu liefern. Neben der verbesserten Steuerung myoelektrischer Prothesen zeigen diese Verfahren auch exzellente Ergebnisse in Bezug auf Neurom- und Phantomschmerzen.

Conventional prosthetic arms suffer from poor controllability and lack of sensory feedback. Owing to the absence of tactile sensory information, prosthetic users must rely on incidental visual and auditory cues. In this study, we investigated the effect of providing tactile perception on motor coordination during routine grasping and grasping under uncertainty. Three transhumeral amputees were implanted with an osseointegrated percutaneous implant system for direct skeletal attachment and bidirectional communication with implanted neuromuscular electrodes. This neuromusculoskeletal prosthesis is a novel concept of artificial limb replacement that allows to extract control signals from electrodes implanted on viable muscle tissue, and to stimulate severed afferent nerve fibers to provide somatosensory feedback. Subjects received tactile feedback using three biologically inspired stimulation paradigms while performing a pick and lift test. The grasped object was instrumented to record grasping and lifting forces and its weight was either constant or unexpectedly changed in between trials. The results were also compared to the no-feedback control condition. Our findings confirm, in line with the neuroscientific literature, that somatosensory feedback is necessary for motor coordination during grasping. Our results also indicate that feedback is more relevant under uncertainty, and its effectiveness can be influenced by the selected neuromodulation paradigm and arguably also the prior experience of the prosthesis user.

We report the use of a bone-anchored, self-contained robotic arm with both sensory and motor components over 3 to 7 years in four patients after transhumeral amputation. The implant allowed for bidirectional communication between a prosthetic hand and electrodes implanted in the nerves and muscles of the upper arm and was anchored to the humerus through osseointegration, the process in which bone cells attach to an artificial surface without formation of fibrous tissue. Use of the device did not require formal training and depended on the intuitive intent of the user to activate movement and sensory feedback from the prosthesis. Daily use resulted in increasing sensory acuity and effectiveness in work and other activities of daily life. (Funded by the Promobilia Foundation and others.).

Removal of benign peripheral nerve sheath tumors (bPNST) represents a surgical challenge. The morphological relation of bPNST and healthy nerve fascicles are of utmost importance for achieving both removal of the entire tumor and preservation of functional integrity of the peripheral nerve. Thus, we intraoperatively assessed the morphological patterns between bPNST and nerve fascicles using photo documentation obtained between January 2009 and September 2021. In 31 patients (20 women and 11 men) with a mean age of 48 ± 18 years a total of 34 bPNST were removed. Four constant morphological patterns between bPNST relatively to nerve fascicles were detected: (1) bPNST is located peripherally (n = 16), (2) it splits the nerve into two main fascicles (n = 5), (3) it totally splits up the nerve out of the nerve’s center (n = 8) und (4) it encloses the nerve and its fascicles (n = 5) without any detectable boundary layer. Histology revealed 28 schwannomas, five neurofibromas, and one perineurioma. The proposed classification reflects the increasing complexity of tumor removal with a higher type number. This might be beneficial for preoperative diagnostics, i.e., high-resolution ultrasound or MRI-tractography, as well as for planning the bPNST’s surgical resection and the possible need for nerve reconstruction.

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.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.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.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]; p0.99), 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.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.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.

Removal of benign peripheral nerve sheath tumors (bPNST) represents a surgical challenge. The morphological relation of bPNST and healthy nerve fascicles are of utmost importance for achieving both removal of the entire tumor and preservation of functional integrity of the peripheral nerve. Thus, we intraoperatively assessed the morphological patterns between bPNST and nerve fascicles using photo documentation obtained between January 2009 and September 2021. In 31 patients (20 women and 11 men) with a mean age of 48 ± 18 years a total of 34 bPNST were removed. Four constant morphological patterns between bPNST relatively to nerve fascicles were detected: (1) bPNST is located peripherally (n = 16), (2) it splits the nerve into two main fascicles (n = 5), (3) it totally splits up the nerve out of the nerve’s center (n = 8) und (4) it encloses the nerve and its fascicles (n = 5) without any detectable boundary layer. Histology revealed 28 schwannomas, five neurofibromas, and one perineurioma. The proposed classification reflects the increasing complexity of tumor removal with a higher type number. This might be beneficial for preoperative diagnostics, i.e., high-resolution ultrasound or MRI-tractography, as well as for planning the bPNST’s surgical resection and the possible need for nerve reconstruction.

The peroneal nerve is one of the most commonly injured nerves of the lower extremity. Nerve grafting has been shown to result in poor functional outcomes. The aim of this study was to evaluate and compare anatomical feasibility as well as axon count of the tibial nerve motor branches and the tibialis anterior motor branch for a direct nerve transfer to reconstruct ankle dorsiflexion. In an anatomical study on 26 human body donors (52 extremities) the muscular branches to the lateral (GCL) and the medial head (GCM) of the gastrocnemius muscle, the soleus muscle (S) as well as the tibialis anterior muscle (TA) were dissected, and each nerve’s external diameter was measured. Nerve transfers from each of the three donor nerves (GCL, GCM, S) to the recipient nerve (TA) were performed and the distance between the achievable coaptation site and anatomic landmarks was measured. Additionally, nerve samples were taken from eight extremities, and antibody as well immunofluorescence staining were performed, primarily evaluating axon count. The average diameter of the nerve branches to the GCL was 1.49 ± 0.37, to GCM 1.5 ± 0.32, to S 1.94 ± 0.37 and to TA 1.97 ± 0.32 mm, respectively. The distance from the coaptation site to the TA muscle was 43.75 ± 12.1 using the branch to the GCL, 48.31 ± 11.32 for GCM, and 19.12 ± 11.68 mm for S, respectively. The axon count for TA was 1597.14 ± 325.94, while the donor nerves showed 297.5 ± 106.82 (GCL), 418.5 ± 62.44 (GCM), and 1101.86 ± 135.92 (S). Diameter and axon count were significantly higher for S compared to GCL as well as GCM, while regeneration distance was significantly lower. The soleus muscle branch exhibited the most appropriate axon count and nerve diameter in our study, while also reaching closest to the tibialis anterior muscle. These results indicate the soleus nerve transfer to be the favorable option for the reconstruction of ankle dorsiflexion, in comparison to the gastrocnemius muscle branches. This surgical approach can be used to achieve a biomechanically appropriate reconstruction, in contrast to tendon transfers which generally only achieve weak active dorsiflexion.

Surgical nerve transfers are used to efficiently treat peripheral nerve injuries, neuromas, phantom limb pain, or improve bionic prosthetic control. Commonly, one donor nerve is transferred to one target muscle. However, the transfer of multiple nerves onto a single target muscle may increase the number of muscle signals for myoelectric prosthetic control and facilitate the treatment of multiple neuromas. Currently, no experimental models are available. This study describes a novel experimental model to investigate the neurophysiological effects of peripheral double nerve transfers to a common target muscle. In 62 male Sprague-Dawley rats, the ulnar nerve of the antebrachium alone (n=30) or together with the anterior interosseus nerve (n=32) was transferred to reinnervate the long head of the biceps brachii. Before neurotization, the motor branch to the biceps’ long head was transected at the motor entry point. Twelve weeks after surgery, muscle response to neurotomy, behavioral testing, retrograde labeling, and structural analyses were performed to assess reinnervation. These analyses indicated that all nerves successfully reinnervated the target muscle. No aberrant reinnervation was observed by the originally innervating nerve. Our observations suggest a minimal burden for the animal with no signs of functional deficit in daily activities or auto-mutilation in both procedures. Furthermore, standard neurophysiological analyses for nerve and muscle regeneration were applicable. This newly developed nerve transfer model allows for the reliable and standardized investigation of neural and functional changes following the transfer of multiple donor nerves to one target muscle.

Surgical nerve transfers are used to efficiently treat peripheral nerve injuries, neuromas, phantom limb pain or improve bionic prosthetic control. Commonly, one donor nerve is transferred to one target muscle. However, the transfer of multiple nerves onto a single target muscle may increase the number of muscle signals for myoelectric prosthetic control and facilitate the treatment of multiple neuromas. Currently, no experimental models are available for multiple nerve transfers to a common target muscle in the upper extremity. This study describes a novel experimental model to investigate the neurophysiological effects of peripheral double nerve transfers. For this purpose, we developed a forelimb model to enable tension-free transfer of one or two donor nerves in the upper extremity. Anatomic dissections were performed to design the double nerve transfer model (n=8). In 62 male Sprague-Dawley rats the ulnar nerve of the antebrachium alone (n=30) or together with the anterior interosseus nerve (n=32) was transferred to reinnervate the long head of the biceps brachii. Before neurotization, the motor branch to the biceps’ long head was transected at the motor entry point and resected up to its original branch to prevent auto-reinnervation. In all animals, coaptation of both nerves to the motor entry point could be performed tension-free. Mean duration of the procedure was 49 ± 13 min for the single nerve transfer and 78 ± 20 min for the double nerve transfer. Twelve weeks after surgery, muscle response to neurotomy, behavioral testing, retrograde labeling and structural analyses were performed to assess reinnervation. These analyses indicated that all nerves successfully reinnervated the target muscle. No aberrant reinnervation was observed by the originally innervating nerve. Our observations suggest a minimal burden for the animal with no signs of functional deficit in daily activities or auto-mutilation in both procedures. Furthermore, standard neurophysiological analyses for nerve and muscle regeneration were applicable. This newly developed nerve transfer model allows for the reliable and standardized investigation of neural and functional changes following the transfer of multiple donor nerves to one target muscle.

For large avians such as vultures, limb loss leads to loss of ambulation and eventually death from malnutrition. Prosthetic devices may replace the limb, however, conventional prosthetic sockets are not feasible in feathered limbs and the extreme stress and strain of unreflected daily use in animals. Osseointegration is a novel technique, where external prosthetic parts are connected directly to a bone anchor to provide a solid skeletal-attachment. This concept provides a high degree of embodiment since osseoperception will provide direct intuitive feedback allowing natural use of the limb in gait and feeding. Here we demonstrate for the first time an osseointegrated bionic reconstruction of a limb in a vulture after a tarsometatarsal amputation with a longterm follow-up.

Summary Background Loss of an extremity at any level has a major impact on a patient’s life. Using bionic reconstruction, extremity function can be restored and the patient reintegrated into daily life. Surgical procedures including selective nerve transfer and anchoring of prostheses into bone are combined with structured rehabilitation and modern prosthetic fitting. The patient is thereby able to use the prostheses intuitively and with multiple degrees of freedom. Methods This article presents the concept and approach for modern bionic reconstruction in detail and the relevant literature. The nerve transfer matrices for targeted muscle reinnervation (TMR) and the concept of osseointegration to optimally fit a patient with a modern prosthesis are described in detail. As a clinical example, the case of a patient who suffered from traumatic amputation and subsequently received TMR in combination with an osseointegrated implant and structured rehabilitation is presented. Results Using bionic reconstruction, basic hand functions can be restored and bimanual dexterity can expand the range of daily activities. Besides this approach to bionic reconstruction, its advantages and disadvantages are compared to hand transplantation. The limitations and perspectives of modern bionic reconstruction are also discussed. Conclusions Bionic reconstruction is a sophisticated method for restoring extremity function and nowadays can be considered a standard of care for all levels of upper extremity amputations. An interdisciplinary approach and structured rehabilitation are necessary to master prosthetic function to ultimately reintegrate patients into daily life.

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. Inaddition, 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 R 2 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.

Die Indikation zum prothetischen Ersatz der oberen Extremitat wurde in den letzten Jahren von der klassischen Amputation auch auf Patienten mit Verlust oder angeborenen Defiziten der Hand- und Armfunktion ausgeweitet. Des Weiteren wurde die Steuerung myoelektrischer Hand- und Armprothesen mittels selektiver Nerventransfers im Stumpfbereich deutlich verbessert. Ubersicht uber die chirurgischen, therapeutischen und prothetischen Moglichkeiten bei Amputationen oder Funktionsverlust der oberen Extremitat. Es erfolgte eine selektive Literaturrecherche unter Berucksichtigung eigener Erfahrungen des klinischen Alltags und Durchsicht von Patientenakten. Die elektive Amputation mit prothetischem Ersatz fuhrt bei Patienten mit funktionsloser Hand zu einer deutlichen Verbesserung der Hand- und Armfunktion und zeigt dadurch auch substanzielle Verbesserungen der Lebensqualitat in diesem speziellen Patientengut. Im Falle einer hohen Amputation ermoglichen selektive Transfers der Nerven des Plexus brachialis auf die verbliebene Stumpfmuskulatur die Etablierung von bis zu 6 Signalgebern, wodurch intuitiv und simultan die verschiedenen prothetischen Gelenke gesteuert werden konnen. Auf diese Weise ist eine deutlich effizientere Steuerung moglich, ohne zwischen den verschiedenen Steuerungsebenen der Prothese wechseln zu mussen. Der prothetische Ersatz der oberen Extremitat stellt nicht nur den Goldstandard nach Amputationen dar, sondern ermoglicht auch fur Patienten mit funktionsloser Hand aufgrund massiver Weichteil- oder Nervenverletzung sowie angeborener Defekte eine funktionelle Wiederherstellung.

Funding Information: The authors would like to thank Aron Cserveny for the preparation of the illustrations included in the manuscript. Furthermore, we thank Xaver Fuchs, Kristina Staudt, Herta Flor, and Martin Diers from Zentralinstitut f?r Seelische Gesundheit Mannheim (Germany) for their input regarding the formulation of the statements evaluating prosthetic embodiment. Funding. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 810346) and the Academy of Finland under project Hi-Fi BiNDIng (No 333149). Publisher Copyright: © Copyright © 2021 Sturma, Hruby, Boesendorfer, Pittermann, Salminger, Gstoettner, Politikou, Vujaklija, Farina and Aszmann. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. Brachial plexus injuries with multiple-root involvement lead to severe and long-lasting impairments in the functionality and appearance of the affected upper extremity. In cases, where biologic reconstruction of hand and arm function is not possible, bionic reconstruction may be considered as a viable clinical option. Bionic reconstruction, through a careful combination of surgical augmentation, amputation, and prosthetic substitution of the functionless hand, has been shown to achieve substantial improvements in function and quality of life. However, it is known that long-term distortions in the body image are present in patients with severe nerve injury as well as in prosthetic users regardless of the level of function. To date, the body image of patients who voluntarily opted for elective amputation and prosthetic reconstruction has not been investigated. Moreover, the degree of embodiment of the prosthesis in these patients is unknown. We have conducted a longitudinal study evaluating changes of body image using the patient-reported Body Image Questionnaire 20 (BIQ-20) and a structured questionnaire about prosthetic embodiment. Six patients have been included. At follow up 2.5–5 years after intervention, a majority of patients reported better BIQ-20 scores including a less negative body evaluation (5 out of 6 patients) and higher vital body dynamics (4 out of 6 patients). Moreover, patients described a strong to moderate prosthesis embodiment. Interestingly, whether patients reported performing bimanual tasks together with the prosthetic hand or not, did not influence their perception of the prosthesis as a body part. In general, this group of patients undergoing prosthetic substitution after brachial plexus injury shows noticeable inter-individual differences. This indicates that the replacement of human anatomy with technology is not a straight-forward process perceived in the same way by everyone opting for it.

Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs., This Perspective argues that technologies for the neural interfacing of robotic devices with the body that have been clinically tested in humans should be leveraged toward the creation of a new generation of high-performance bionic limbs.

Background: Modern surgery demands high-quality and reproducibility. Due to new working directives, resident duty hours have been restricted and evidence exists that pure on-the-job training provides insufficient exposure. We hypothesize that supplemental simulations in animal models provide a realistic training to augment clinical experiences. This study reviews surgical training models, their costs and survey results illustrating academic acceptance. Methods: Animal models were identified by literature research. Costs were analyzed from multiple German and Austrian training programs. A survey on their acceptance was conducted among faculty and medical students. Results: 915 articles were analyzed, thereof 91 studies described in-vivo animal training models, predominantly for laparoscopy (30%) and microsurgery (24%). Cost-analysis revealed single-training costs between 307€ and 5861€ depending on model and discipline. Survey results illustrated that 69% of the participants had no experience, but 66% would attend training under experienced supervision. Perceived public acceptance was rated intermediate by medical staff and students (4.26; 1 – low, 10 high). Conclusion: Training in animals is well-established and was rated worth attending in a majority of a representative cohort to acquire key surgical skills, in light of reduced clinical exposure. Animal models may therefore supplement the training of tomorrow’s surgeons to overcome limited hands-on experience until virtual simulations can provide such educational tools.

The objective of this surgery is to achieve early reinnervation of the intrinsic hand muscles through axons of the median nerve, preventing irreversible atrophy of the muscle tissue. The nerve transfer is achieved via a babysitter graft, which is sutured end-to-side to the donor as well as the recipient nerve. The procedure is carried out in combination with a proximal reconstruction of the ulnar nerve.High-grade lesions of the ulnar nerve without spontaneous regeneration, particularly when lesions are located proximally and/or when patients present late.Irreversible denervation of the intrinsic muscles; weakness or palsy of the thenar branch.The approach is taken through a longitudinal incision over the volar wrist. The deep branch of the ulnar nerve as well as the thenar branch of the median nerve are visualized after transection of the flexor retinaculum. An autologous graft is then placed between the two nerves, sutured to the donor (thenar branch) as well as the recipient nerve (ulnar deep branch) via an epineural window in an end-to-side manner. This facilitates timely regeneration of motor axons from the median nerve into the intrinsic muscles, thereby preventing irreversible degeneration. Through the end-to-side nerve coaptation, damage to the donor nerve is reduced to a minimum. At the same time reconstruction of the ulnar nerve is performed proximally to the lesion, facilitating original reinnervation of the intrinsic muscles at a later time.Postoperatively, Penrose drains are placed and a sterile hand dressing is applied. Drain removal and dressing change are performed on the first day, suture removal after 2 weeks. Physical therapy for mobility of the joints can be started as early as 1 week after surgery. After the first signs of motor and/or sensory reinnervation, a targeted retraining of daily skills should be initiated.This procedure has so far been reported on three patients with high-grade ulnar nerve injury. After a follow-up duration of 6 years, each achieved muscle strength of ≥ M3, with good to excellent overall regeneration according to the modified Bishop rating scale.OPERATIONSZIEL: Ziel dieser Operation ist eine frühzeitige Innervation der intrinsischen Handmuskulatur durch Fasern des N. medianus, um einer irreversiblen Atrophie des Muskelgewebes vorzubeugen. Der Nerventransfer erfolgt mittels Babysitter-Interponat, welches jeweils End-zu-Seit an Spender- und Empfängernerv koaptiert wird. Der Eingriff wird kombiniert mit einer proximalen Rekonstruktion des N. ulnaris.Hochgradige Läsionen des N. ulnaris ohne spontane Regeneration, insbesondere bei proximaler Läsionshöhe und/oder später Patientenvorstellung.Irreversible Denervation der intrinsischen Muskulatur; Schwäche oder Ausfall des R. thenaris.Der Zugang erfolgt über dem beugeseitigen Handgelenk durch eine longitudinale Inzision. Der R. profundus des N. ulnaris sowie der R. thenaris des N. medianus werden nach Spalten des Retinaculum flexorum dargestellt. Es erfolgt eine Verbindung der beiden Nerven über ein autologes Interponat, welches jeweils in End-zu-Seit-Manier über ein epineurales Fenster an den Spender- (R. thenaris) und den Empfängernerv (R. profundus) koaptiert wird. Dies ermöglicht die zeitgerechte Regeneration einiger motorischer Medianusaxone in die intrinsische Muskulatur, um einer irreversiblen Degeneration vorzubeugen. Aufgrund der End-zu-Seit-Nervennaht wird der Schaden des Spendernervs auf ein Minimum reduziert. Durch die gleichzeitig durchgeführte Rekonstruktion des N. ulnaris auf Höhe der Läsion wird im späteren Verlauf auch eine autochthone Reinnervation der intrinsischen Muskulatur ermöglicht.Postoperativ werden Laschen eingebracht und ein steriler Handverband angelegt. Erster Verbandswechsel und Zug der Laschen am ersten postoperativen Tag, Nahtentfernung in der Regel nach 2 Wochen. Bereits nach 1 Woche kann die ergotherapeutische Beübung zum Erhalt der Gelenkbeweglichkeit erfolgen. Nach den ersten Zeichen der motorischen und/oder sensiblen Reinnervation erfolgt eine zielgerichtete Physiotherapie zum Wiedererlernen der alltäglichen Handfunktion.Diese Technik wurde bisher an 3 Patienten mit hochgradiger Läsion des N. ulnaris vorgestellt. Bei einer Follow-up-Zeit von 6 Jahren konnten alle Patienten Muskelkraft von ≥ M3 erlangen, mit allgemein gutem bis exzellentem Ergebnis anhand der modifizierten Bishop Rating Scale.

Global brachial plexopathies including multiple nerve root avulsions may result in complete upper limb paralysis despite surgical treatment. Bionic reconstruction, which includes the elective amputation of the functionless hand and its replacement with a mechatronic device, has been described for the transradial level. Here, we present for the first time that patients with global brachial plexus avulsion injuries and lack of biological shoulder and elbow function benefit from above-elbow amputation and prosthetic rehabilitation. Between 2012 and 2017, forty-five patients with global brachial plexus injuries approached our centre, of which nineteen (42.2%) were treated with bionic reconstruction. While fourteen patients were amputated at the transradial level, the entire upper limb was replaced with a prosthetic arm in a total of five patients. Global upper extremity function before and after bionic arm substitution was assessed using two objective hand function tests, the action research arm test (ARAT), and the Southampton hand assessment procedure (SHAP). Other outcome measures included the DASH questionnaire, VAS to assess deafferentation pain and the SF-36 health survey to evaluate changes in quality of life. Using a hybrid prosthetic arm mean ARAT scores improved from 0.6 &plusmn, 1.3 to 11.0 &plusmn, 6.7 (p = 0.042) and mean SHAP scores increased from 4.0 &plusmn, 3.7 to 13.8 &plusmn, 9.2 (p = 0.058). After prosthetic arm replacement mean DASH scores improved from 52.5 &plusmn, 9.4 to 31.2 &plusmn, 9.8 (p = 0.003). Deafferentation pain decreased from mean VAS 8.5 &plusmn, 1.0 to 6.7 &plusmn, 2.1 (p = 0.055), while the physical and mental component summary scale as part of the SF-36 health survey improved from 32.9 &plusmn, 6.4 to 40.4 &plusmn, 9.4 (p = 0.058) and 43.6 &plusmn, 8.9 to 57.3 &plusmn, 5.5 (p = 0.021), respectively. Bionic reconstruction can restore simple but robust arm and hand function in longstanding brachial plexus patients with lack of treatment alternatives.

There is a large body of evidence demonstrating high rates of prosthesis abandonment in the upper extremity. However, these surveys were conducted years ago, thus the influence of recent refinements in prosthetic technology on acceptance is unknown. This study aims to gather current data on prosthetic usage, to assess the effects of these advancements.A questionnaire was sent to 68 traumatic upper limb amputees treated within the Austrian Trauma Insurance Agency between the years 1996 and 2016. Responses were grouped by the year of amputation to assess the effect of time.The rejection rate at all levels of amputation was 44%. There was no significant difference in acceptance between responders amputated before or after 2006 (The advancements of the last decade in the arena of upper limb prosthetics have not yet achieved a significant change in prosthetic abandonment within this study cohort. Although academic solutions have been presented to tackle patient's complaints, clinical reality still shows high rejection rates of cost-intensive prosthetic devices.Implications for rehabilitationAbandonment rates in prosthetic rehabilitation after upper limb amputation have shown to be 50% and higher.The advancements of the last decade in the arena of upper limb prosthetics have not yet achieved a significant change in prosthetic abandonment.Well-structured and patient-tailored prosthetic training as well as ensuring the amputee's active participation in the decision making process will most likely improve prosthetic acceptance.

Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported.Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS).Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg).Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.

BACKGROUND Plexiform neurofibromas (PN) are a hallmark feature of Neurofibromatosis type 1 (NF1). 10% of PN undergo malignant transformation. As malignant peripheral nerve sheath tumors are a leading cause of death in NF1-patients, early detection of malignancy is essential. 2-deoxy-2-[ 18F]fluoro-D-glucose [18F]FDG PET/CT imaging is used in patients with NF1 to judge malignant transformation. AIMS: The present study evaluated [18F]FDG PET/MRI in pediatric NF1 patients at high risk for MPNST and its utility as a possible screening tool for malignant transformation of yet asymptomatic lesions. METHODS Patients aged 0-25 with symptomatic and asymptomatic neurofibromas who underwent PET/MRI from 2014 to 2021 were included. Chart review of imaging data, clinical and histological findings was performed retrospectively. RESULTS 41 patients (18 female) with a median age at first PET/MRI of 16.87 years (6.21-24.41) were included. 40 lesions were operated as indicated by clinical (e.g. pain, rapid growth) or imaging findings. Based on histopathological analysis 7 lesions in 4 patients were categorized as malignant, 3 as atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP). 4/7 malignant and 2/3 ANNUBP lesions were asymptomatic (i.e. without rapid growth, pain, neurologic dysfunction). 5/7 symptomatic tumors were without significant FDG-PET and proven benign by histology. 18 lesions (2 symptomatic) in 9 patients that showed an increased uptake suspect of malignant transformation were histologically classified as benign. None of the patients died during follow-up, 1 symptomatic MPNST patient received postsurgical radio- and chemotherapy. CONCLUSION Our data indicate that malignant transformation of PN also occurs in asymptomatic patients. [18F]FDG PET/MRI is feasible in pediatric and adolescent patients with the tumor predisposition syndrome NF1 and is an alternative to PET/CT when assessing for malignancy thereby drastically reducing radiation exposure. Early detection through screening of high-risk NF1 patients with [18F]FDG PET/MRI could potentially increase overall survival by facilitating early curative resection.

OBJECTIVEGlobal brachial plexus lesions with multiple root avulsions are among the most severe nerve injuries, leading to lifelong disability. Fortunately, in most cases primary and secondary reconstructions provide a stable shoulder and restore sufficient arm function. Restoration of biological hand function, however, remains a reconstructive goal that is difficult to reach. The recently introduced concept of bionic reconstruction overcomes biological limitations of classic reconstructive surgery to restore hand function by combining selective nerve and muscle transfers with elective amputation of the functionless hand and its replacement with a prosthetic device. The authors present their treatment algorithm for bionic hand reconstruction and report on the management and long-term functional outcomes of patients with global brachial plexopathies who have undergone this innovative treatment.METHODSThirty-four patients with posttraumatic global brachial plexopathies leading to loss of hand function consulted the Center for Advanced Restoration of Extremity Function between 2011 and 2015. Of these patients, 16 (47%) qualified for bionic reconstruction due to lack of treatment alternatives. The treatment algorithm included progressive steps with the intent of improving the biotechnological interface to allow optimal prosthetic hand replacement. In 5 patients, final functional outcome measurements were obtained with the Action Arm Research Test (ARAT), the Southampton Hand Assessment Procedure (SHAP), and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire.RESULTSIn all 5 patients who completed functional assessments, partial hand function was restored with bionic reconstruction. ARAT scores improved from 3.4 ± 4.3 to 25.4 ± 12.7 (p = 0.043; mean ± SD) and SHAP scores improved from 10.0 ± 1.6 to 55 ± 19.7 (p = 0.042). DASH scores decreased from 57.9 ± 20.6 to 32 ± 28.6 (p = 0.042), indicating decreased disability.CONCLUSIONSThe authors present an algorithm for bionic reconstruction leading to useful hand function in patients who lack biological treatment alternatives for a stiff, functionless, and insensate hand resulting from global brachial plexopathies.

In patients with global brachial plexus injury and lack of biological treatment alternatives, bionic reconstruction, including the elective amputation of the functionless hand and its replacement with a prosthesis, has recently been described. Optimal prosthetic function depends on a structured rehabilitation protocol, as residual muscle activity in a patient’s arm is later translated into prosthetic function. Surface electromyographic (sEMG) biofeedback has been used during rehabilitation after stroke, but has so far not been used in patients with complex peripheral nerve injuries. Here, we present our rehabilitation protocol implemented in patients with global brachial plexus injuries suitable for bionic reconstruction, starting from identification of sEMG signals to final prosthetic training. This structured rehabilitation program facilitates motor relearning, which may be a cognitively debilitating process after complex nerve root avulsion injuries, aberrant re-innervation and extra-anatomical reconstruction (as is the case with nerve transfer surgery). The rehabilitation protocol using sEMG biofeedback aids in the establishment of new motor patterns as patients are being made aware of the advancing re-innervation process of target muscles. Additionally, faint signals may also be trained and improved using sEMG biofeedback, rendering a clinically "useless" muscle (exhibiting muscle strength M1 on the British Medical Research Council [BMRC] scale) eligible for dexterous prosthetic hand control. Furthermore, functional outcome scores after successful bionic reconstruction are presented in this article.

After severe nerve injuries, selective nerve transfers provide an opportunity to restore motor and sensory function. Functional recovery depends both on the successful re-innervation of the targets in the periphery and on the motor re-learning process entailing cortical plasticity. While there is an increasing number of methods to improve rehabilitation, their routine implementation in a clinical setting remains a challenge due to their complexity and long duration. Therefore, recommendations for rehabilitation strategies are presented with the aim of guiding medical doctors and therapists through the long-lasting rehabilitation process and providing step-by-step instructions for supporting motor re-learning. Directly after nerve transfer surgery, no motor function is present, and therapy should focus on promoting activity in the sensory-motor cortex areas of the paralyzed body part. After about two to six months (depending on the severity and modality of injury, the distance of nerve regeneration and many other factors), the first motor activity can be detected via electromyography (EMG). Within this phase of rehabilitation, multimodal feedback is used to re-learn the motor function. This is especially critical after nerve transfers, as muscle activation patterns change due to the altered neural connection. Finally, muscle strength should be sufficient to overcome gravity/resistance of antagonistic muscles and joint stiffness, and more functional tasks can be implemented in rehabilitation.

Targeted muscle reinnervation (TMR) amplifies the electrical activity of nerves at the stump of amputees by redirecting them in remnant muscles above the amputation. The electrical activity of the reinnervated muscles can be used to extract natural control signals. Nonetheless, current control systems, mainly based on noninvasive muscle recordings, fail to provide accurate and reliable control over time. This is one of the major reasons for prosthetic abandonment. This prospective interventional study includes three unilateral above-elbow amputees and reports the long-term (2.5 years) implant of wireless myoelectric sensors in the reinnervation sites after TMR and their use for control of robotic arms in daily life. It therefore demonstrates the clinical viability of chronically implanted myoelectric interfaces that amplify nerve activity through TMR. The patients showed substantial functional improvements using the implanted system compared with control based on surface electrodes. The combination of TMR and chronically implanted sensors may drastically improve robotic limb replacement in above-elbow amputees.

Research on machine learning approaches for upper limb prosthesis control has shown impressive progress. However, translating these results from the lab to patient's everyday lives remains a challenge, because advanced control schemes tend to break down under everyday disturbances, such as electrode shifts. Recently, it has been suggested to apply adaptive transfer learning to counteract electrode shifts using as little newly recorded training data as possible. In this paper, we present a novel, simple version of transfer learning and provide the first user study demonstrating the effectiveness of transfer learning to counteract electrode shifts. For this purpose, we introduce the novel Box and Beans test to evaluate prosthesis proficiency and compare user performance with an initial simple pattern recognition system, the system under electrode shifts, and the system after transfer learning. Our results show that transfer learning could significantly alleviate the impact of electrode shifts on user performance in the Box and Beans test.