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

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

[Prosthetic Fitting Concepts after Major Amputation in the Upper Limb - an Overview of Current Possibilities]. / Prothetische Versorgungskonzepte nach Majoramputation der oberen Extremität ­ eine Übersicht gegenwärtiger Möglichkeiten.

BACKGROUND: The upper extremity and particularly the hands are crucial for patients in interacting with their environment, therefore amputations or severe damage with loss of hand function significantly impact their quality of life. In cases where biological reconstruction is not feasible or does not lead to sufficient success, bionic reconstruction plays a key role in patient care. Classical myoelectric prostheses are controlled using two signals derived from surface electrodes in the area of the stump muscles. Prosthesis control, especially in high amputations, is then limited and cumbersome. The surgical technique of Targeted Muscle Reinnervation (TMR) offers an innovative solution: The major arm nerves that have lost their target organs due to amputation are rerouted to muscles in the stump area. This enables the establishment of cognitive control signals that allow significantly improved prosthesis control. PATIENTS/MATERIALS AND METHODS: A selective literature review on TMR and bionic reconstruction was conducted, incorporating relevant articles and discussing them considering the clinical experience of our research group. Additionally, a clinical case is presented. RESULTS: Bionic reconstruction combined with Targeted Muscle Reinnervation enables intuitive prosthetic control with simultaneous movement of various prosthetic degrees of freedom and the treatment of neuroma and phantom limb pain. Long-term success requires a high level of patient compliance and intensive signal training during the prosthetic rehabilitation phase. Despite technological advances, challenges persist, especially in enhancing signal transmission and integrating natural sensory feedback into bionic prostheses. CONCLUSION: TMR surgery represents a significant advancement in the bionic care of amputees. Employing selective nerve transfers for signal multiplication and amplification, opens up possibilities for improving myoelectric prosthesis function and thus enhancing patient care. Advances in the area of external prosthetic components, improvements in the skeletal connection due to osseointegration and more fluid signal transmission using wireless, fully implanted electrode systems will lead to significant progress in bionic reconstruction, both in terms of precision of movement and embodiment.

Axonal mapping of the motor cranial nerves.

Basic behaviors, such as swallowing, speech, and emotional expressions are the result of a highly coordinated interplay between multiple muscles of the head. Control mechanisms of such highly tuned movements remain poorly understood. Here, we investigated the neural components responsible for motor control of the facial, masticatory, and tongue muscles in humans using specific molecular markers (ChAT, MBP, NF, TH). Our findings showed that a higher number of motor axonal population is responsible for facial expressions and tongue movements, compared to muscles in the upper extremity. Sensory axons appear to be responsible for neural feedback from cutaneous mechanoreceptors to control the movement of facial muscles and the tongue. The newly discovered sympathetic axonal population in the facial nerve is hypothesized to be responsible for involuntary control of the muscle tone. These findings shed light on the pivotal role of high efferent input and rich somatosensory feedback in neuromuscular control of finely adjusted cranial systems.

Nerve transfer reversal to treat co-contraction after anatomic brachial plexus reconstruction and Oberlin transfer: A case report.

Distal nerve transfers to restore elbow flexion have become standard of care in brachial plexus reconstruction. The purpose of this report is to draw attention to intractable co-contraction as a rare but significant adverse event of distal nerve transfers. Here we report of treatment of a disabling co-contraction of the brachialis muscle and wrist/finger flexors after median to brachialis fascicular transfer in a 61-year-old male patient. The primary injury was an postganglionic lesion of roots C5/C6 and a preganglionic injury of C7/C8 with intact root Th1 after a motor bicycle accident. After upper brachial plexus reconstruction (C5/C6 to suprascapular nerve and superior trunk) active mobility in the shoulder joint (supraspinatus, deltoid) could be restored. However, due to lacking motor recovery of elbow flexion the patient underwent additional median to brachialis nerve transfer. Shortly after, active elbow flexion commenced with rapid recovery to M4 at 9 months postoperatively. However, despite intensive EMG triggered physiotherapy the patient could not dissociate hand from elbow function and was debilitated by this iatrogenic co-contraction. After preoperative ultrasound-guided block resulted in preserved biceps function, the previously transferred median nerve fascicle was reversed. This was done by dissecting the previous nerve transfer of the median nerve fascicle to the brachialis muscle branch and adapting the fascicles to their original nerve. Postoperatively, the patient was followed up for 10 months without a complication and maintained M4 elbow flexion with independent strong finger flexion. Distal nerve transfers are an excellent option to restore function, however, in some patients cognitive limitations may prevent cortical reorganization and lead to disturbing co-contractions.

Nerve Transfers for Brachial Plexus Reconstruction in Patients over 60 Years.

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.

Axonal mapping of motor and sensory components within the ulnar nerve and its branches.

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.

Newly identified axon types of the facial nerve unveil supplemental neural pathways in the innervation of the face.

INTRODUCTION: Neuromuscular control of the facial expressions is provided exclusively via the facial nerve. Facial muscles are amongst the most finely tuned effectors in the human motor system, which coordinate facial expressions. In lower vertebrates, the extracranial facial nerve is a mixed nerve, while in mammals it is believed to be a pure motor nerve. However, this established notion does not agree with several clinical signs in health and disease. OBJECTIVES: To elucidate the facial nerve contribution to the facial muscles by investigating axonal composition of the human facial nerve. To reveal new innervation pathways of other axon types of the motor facial nerve. METHODS: Different axon types were distinguished using specific molecular markers (NF, ChAT, CGRP and TH). To elucidate the functional role of axon types of the facial nerve, we used selective elimination of other neuronal support from the trigeminal nerve. We used retrograde neuronal tracing, three-dimensional imaging of the facial muscles, and high-fidelity neurophysiological tests in animal model. RESULTS: The human facial nerve revealed a mixed population of only 85% motor axons. Rodent samples revealed a fiber composition of motor, afferents and, surprisingly, sympathetic axons. We confirmed the axon types by tracing the originating neurons in the CNS. The sympathetic fibers of the facial nerve terminated in facial muscles suggesting autonomic innervation. The afferent fibers originated in the facial skin, confirming the afferent signal conduction via the facial nerve. CONCLUSION: These findings reveal new innervation pathways via the facial nerve, support the sympathetic etiology of hemifacial spasm and elucidate clinical phenomena in facial nerve regeneration.

Distal Nerve Transfers in High Peroneal Nerve Lesions: An Anatomical Feasibility Study.

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.

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

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

Proof of concept for multiple nerve transfers to a single 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. 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.

[Babysitter nerve transfer from the thenar branch to the deep terminal branch of the ulnar nerve : An option to preserve the intrinsic hand muscles in proximal lesions of the ulnar nerve]. / "Babysitter"-Nerventransfer vom R. thenaris zum R. profundus nervi ulnaris : Eine Option zum Erhalt der intrinsischen Handmuskulatur bei hohen Läsionen des N. ulnaris.

OBJECTIVE: 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. INDICATIONS: High-grade lesions of the ulnar nerve without spontaneous regeneration, particularly when lesions are located proximally and/or when patients present late. CONTRAINDICATIONS: Irreversible denervation of the intrinsic muscles; weakness or palsy of the thenar branch. SURGICAL TECHNIQUE: 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. POSTOPERATIVE MANAGEMENT: 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. RESULTS: 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.

Selective Denervation of the Facial Dermato-Muscular Complex in the Rat: Experimental Model and Anatomical Basis.

The facial dermato-muscular system consists of highly specialized muscles tightly adhering to the overlaying skin and thus form a complex morphological conglomerate. This is the anatomical and functional basis for versatile facial expressions, which are essential for human social interaction. The neural innervation of the facial skin and muscles occurs via branches of the trigeminal and facial nerves. These are also the most commonly pathologically affected cranial nerves, often requiring surgical treatment. Hence, experimental models for researching these nerves and their pathologies are highly relevant to study pathophysiology and nerve regeneration. Experimental models for the distinctive investigation of the complex afferent and efferent interplay within facial structures are scarce. In this study, we established a robust surgical model for distinctive exploration of facial structures after complete elimination of afferent or efferent innervation in the rat. Animals were allocated into two groups according to the surgical procedure. In the first group, the facial nerve and in the second all distal cutaneous branches of the trigeminal nerve were transected unilaterally. All animals survived and no higher burden was caused by the procedures. Whisker pad movements were documented with video recordings 4 weeks after surgery and showed successful denervation. Whole-mount immunofluorescent staining of facial muscles was performed to visualize the innervation pattern of the neuromuscular junctions. Comprehensive quantitative analysis revealed large differences in afferent axon counts in the cutaneous branches of the trigeminal nerve. Axon number was the highest in the infraorbital nerve (28,625 ± 2,519), followed by the supraorbital nerve (2,131 ± 413), the mental nerve (3,062 ± 341), and the cutaneous branch of the mylohyoid nerve (343 ± 78). Overall, this surgical model is robust and reliable for distinctive surgical deafferentation or deefferentation of the face. It may be used for investigating cortical plasticity, the neurobiological mechanisms behind various clinically relevant conditions like facial paralysis or trigeminal neuralgia as well as local anesthesia in the face and oral cavity.

Case Report: Bionic Reconstruction in an Adult With Obstetric Brachial Plexus Injury.

Introduction: Many adults who had a severe Narakas IV obstetric brachial plexus injury (OBPI) suffer from extensive impairments in daily living due to limited hand-arm function. The dramatic loss of axonal support at this very early age of development often render the entire extremity a biologic wasteland and reconstructive methods and therapies often fail to recover any functional hand use. In this scenario bionic reconstruction, including an elective amputation and a subsequent prosthetic fitting, may enable functional improvement in adults suffering from the consequences of such severe brachial plexus injuries. We here describe our experience in treating such patients and lay out the surgical rational and rehabilitation protocol exemplified in one patient. Case Presentation/Methods: A 27-year-old adult with a unilateral OBPI contacted our center. He presented with globally diminished function of the affected upper extremity with minimal hand activity, resulting in an inability to perform various tasks of daily living. No biological reconstructive efforts were available to restore meaningful hand function. An interdisciplinary evaluation, including a psychosocial assessment, was used to assess eligibility for bionic reconstruction. Before the amputation and after the prosthetic fitting functional assessments and self-reported questionnaires were performed. Results: One month after the amputation and de-rotation osteotomy of the humerus the patient was fitted with a myoelectric prosthesis. At the 1.5 year-follow-up assessment, the patient presented with a distinct improvement of function: the ARAT improved from 12 to 20 points, SHAP score improved from 8 to 29, and the DASH value improved from 50 to 11.7. The average wearing times of the prosthesis were 5 to 6 h per day (on 4-5 days a week). Discussion: The options for adults suffering from the consequences of severe OBPIs to improve function are limited. In selected patients in whom the neurological deficit is so severe that biologic hand function is unsatisfactory, an elective amputation and subsequent restoration of the hand with mechatronic means may be an option. The follow-up results indicate that this concept can indeed lead to solid hand function and independence in daily activities after amputation, subsequent prosthetic fitting, and rehabilitation.

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

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