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ZusammenfassungDie Behandlung von peripheren Nervenverletzungen und Kompressionssyndromen erfordert eine rasche und präzise Diagnose. Nervenpathologien korrekt zu identifizieren ist klinisch jedoch oft diffizil, womit wichtige Zeit bis zur fachgerechten Therapie verlorengeht. In diesem Positionspaper der deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie (DAM) wird der derzeitige Status Quo zur Diagnostik von peripheren Nerven bei traumatischen Läsionen und Kompressionssyndromen analysiert. Hierbei wurde der Stellenwert der klassischen klinischen Diagnostik in Zusammenschau mit Elektrophysiologie, hochauflösendem Nervenultraschall und Magnetresonanz-Neurographie bewertet sowie die Mitglieder der DAM zu ihrem diagnostischen Zugang befragt. Die beschriebenen Inhalte wurden im Zuge eines Konsensusworkshops anlässlich der 42. Jahrestagung der DAM 2021 in Graz erarbeitet.

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.

OBJECTIVE Until recently, autologous sensory nerve grafting has remained the gold-standard technique in peripheral nerve reconstruction. However, there are several disadvantages to these grafts, such as donor site morbidity, limited availability, and a qualitative mismatch. Building on this shortage, a new concept, the fascicular shift procedure, was proposed and successfully demonstrated nerve regeneration in a rat nerve injury model. This approach involves harvesting a fascicular group distal to a peripheral nerve injury and shifting it to bridge the defect. The present study aimed to evaluate the clinical applicability of this technique in brachial plexus reconstruction. METHODS The supra- and infraclavicular nerves of the brachial plexus were bilaterally explored in 18 formalin-fixed cadaveric specimens. Following dissection, their fascicular shifting potential was evaluated. The medial antebrachial cutaneous and sural nerves were investigated and used as references for the required cross-sectional area of potential nerve grafts. Furthermore, 29 brachial plexus injuries, which qualified for surgical repair, were subjected to retrospective analysis. The intraoperatively measured lengths of the harvested and ultimately transplanted nerve grafts served as a basis to assess graft requirements in brachial plexus lesions. RESULTS The transplanted nerve grafts measured a total length of 51.9 ± 28.1 cm in brachial plexus injuries. The individual inserted nerve grafts averaged 10.3 ± 5.1 cm. In the anatomical exploration, the ulnar and median nerves qualified for fascicular shifting. Their fascicular graft lengths measured 26.6 ± 2.5 cm and 24.8 ± 5.2 cm, respectively. The long thoracic, suprascapular, musculocutaneous, thoracodorsal, and axillary nerves were not suitable for fascicular shifting. The sensory graft length of the medial antebrachial cutaneous nerve measured 20.6 ± 3.4 cm. CONCLUSIONS In the surgical reconstruction of brachial plexus injuries, fascicular shifting of the ulnar and median nerves provides sufficient donor material. Even though potential donor length is limited in the radial nerve, it may still help to expand the surgical armamentarium in selected clinical scenarios. Overall, the fascicular shift procedure presents a novel alternative to allow modality-matched grafting in the reconstruction of large proximal nerve defects and was found to be an attractive option in brachial plexus reconstruction.

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.

Background Bilateral proximal upper limb loss is a dramatic life-changing event. Replacement of the lost function with prosthetic arms, including multiple mechatronic joints, has remained a challenge from the control, comfort, and pain management perspectives. Targeted muscle reinnervation (TMR) is a peripheral nerve surgical procedure proposed to improve the intuitive control of the prosthetic arm and for neuroma and phantom pain management. Moreover, osseointegrated percutaneous implants (OPIs) allow for direct skeletal attachment of the prosthetic arm, ensuring freedom of movement to the patient’s residual articulations. Case Description We have reported the first combined application of TMR and an OPI to treat a 24-year-old woman with a bilateral amputation at the shoulder level on the right side and at the very proximal transhumeral level on the left side. TMR was performed bilaterally in a single day, accounting for the peculiar patient’s anatomy, as preparatory stage to placement of the OPI, and considering the future availability of implantable electromyographic sensors. The 2 OPI surgeries on the left side were completed after 8.5 months, and prosthetic treatment was completed 17 months after TMR. Conclusions The use of TMR resolved the phantom pain bilaterally and the right-side neuroma pain. It had also substantially reduced the left side neuroma pain. The actual prosthetic control result was intuitive, although partially different from expectations. At 2 years after TMR, the patient reported improvement in essential activities of daily living, with a remarkable preference for the OPI prosthesis. Only 1 suspected case of superficial infection was noted, which had resolved. Overall, this combined treatment required a highly competent multidisciplinary team and exceptional commitment by the patient and her family.

Osseointegration is a relatively new technique for prosthetic limb attachment that offers various improvements for patients with amputation and facilitates joint preservation. We present a case of implant loosening during rehabilitation in a patient with transtibial amputation that was successfully managed through a combination of measures, aiming to promote re-osseointegration of the implant.Not much is known about structured management of adverse events after osseointegration. Septic or aseptic loosening is currently regarded as implant failure, prompting removal and possible re-implantation at a later stage. The objective of this case report was to evaluate the feasibility of salvaging a loosened implant.Case report.A novel treatment approach was employed to enable renewed osseointegration of the implant. First, the bone-implant interface was disrupted and renewed through axial rotation and distal repositioning of the implant. Afterwards, extracorporal shockwave therapy and antibiotic treatment were administered. Prosthetic rehabilitation was then started anew. Regular follow-up x-rays and clinical evaluations were conducted, including standardized outcome tests.These combined measures led to a successful re-osseointegration of the implant. In a 21-month follow-up, the patient regained a stable and secure gait pattern, using his prosthesis every day for 15 hours and scoring above average on standardized outcome measures.This represents the first report of implant salvage after failed primary osseointegration. As the associated risks of this novel treatment are very low, investigations are warranted to evaluate this approach on a larger scale.

Zusammenfassung. Neuropathische Schmerzen können auch in Folge iatrogener Nervenläsionen auftreten. Iatrogene oder traumatische Nervenläsionen führen häufig zu erheblichen funktionellen Beeinträchtigungen und können chronische neuropathische Schmerzen nach sich ziehen. Nur wer sich regelmässig mit der Problematik peripherer Nervenläsionen auseinandersetzt, kann auf einen ausreichend grossen diagnostischen und chirurgischen Erfahrungsschatz zurückgreifen, um rasch und effizient die richtige Diagnose und gegebenenfalls Indikation zur optimalen rekonstruktiven Therapie zu stellen. Zeit ist meist der Hauptfaktor, welcher über den Erfolg der Schadensbehebung oder zumindest -begrenzung entscheidet. Chirurgen anderer Fachdisziplinen, die nicht routinemässig, sondern rein komplikationsbedingt plötzlich mit dieser spezifischen Problemstellung konfrontiert sind, benötigen daher einen klaren Überblick über die adäquate Abklärung und Rekonstruktionsmöglichkeiten, um ihren Patienten zeitgerecht die richtige Diagnostik und Therapie zukommen zu lassen. In dieser Übersichtsarbeit sollen einerseits jene Operationen aufgelistet werden, bei denen besonders häufig iatrogene Nervenläsionen dokumentiert wurden. Des Weiteren möchten wir gemäss unseren Erfahrungen aus dem Spezialgebiet der peripheren Nervenchirurgie über die richtige und effiziente Diagnostik sowie die rekonstruktiven Möglichkeiten informieren. Mit funktionierender interdisziplinärer Zusammenarbeit und einem entsprechenden diagnostischen und therapeutischen Vorgehen lassen sich die Ergebnisse nach iatrogenen Nervenverletzungen verbessern und somit auch eventuelle juristische Konsequenzen verhindern.

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.

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.

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.

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

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.

Targeted muscle reinnervation (TMR) is a surgical procedure, whereby nerves without muscle targets after extremity amputation are transferred to residual stump muscles. Thereby, the control of prosthesis is improved by increasing the number of independent muscle signals. The authors describe indications for TMR to improve prosthetic control and present standard nerve transfer matrices suitable for transhumeral and glenohumeral amputees. In addition, the perioperative procedure is described, including preoperative testing, surgical approach, and postoperative rehabilitation. Based on recent neurophysiological insights and technological advances, they present an outlook into the future of prosthetic control combining TMR and implantable electromyographic technology.

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.