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1.
J Neurosci ; 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216502

RESUMO

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.

2.
N Engl J Med ; 382(18): 1732-1738, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32348644

RESUMO

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.).


Assuntos
Amputação Cirúrgica/reabilitação , Amputação Traumática/reabilitação , Membros Artificiais , Neuroestimuladores Implantáveis , Desenho de Prótese , Robótica , Adulto , Membros Artificiais/efeitos adversos , Humanos , Úmero/lesões , Úmero/cirurgia , Masculino , Pessoa de Meia-Idade , Osseointegração
3.
Histochem Cell Biol ; 159(1): 23-45, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36201037

RESUMO

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


Assuntos
Neurônios , Medula Espinal , Humanos , Imuno-Histoquímica , Imunofluorescência , Doadores de Tecidos
4.
Microsurgery ; 43(7): 717-721, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37349939

RESUMO

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.

5.
Clin Orthop Relat Res ; 480(6): 1191-1204, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35202032

RESUMO

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


Assuntos
Membros Artificiais , Animais , Cadáver , Cães , Eletrodos Implantados , Eletromiografia , Estudos de Viabilidade , Humanos , Inflamação , Coelhos , Ovinos
6.
J Hand Ther ; 35(1): 58-66, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33250398

RESUMO

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


Assuntos
Amputados , Membros Artificiais , Amputação Cirúrgica/reabilitação , Amputados/reabilitação , Braço , Biorretroalimentação Psicológica , Eletromiografia , Humanos , Músculo Esquelético , Extremidade Superior
7.
Orthopade ; 50(1): 14-23, 2021 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-33231741

RESUMO

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.


Assuntos
Cotos de Amputação/cirurgia , Nervos Periféricos/cirurgia , Membro Fantasma , Amputação Cirúrgica , Extremidades , Humanos
8.
J Neurol Neurosurg Psychiatry ; 91(8): 879-888, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32487526

RESUMO

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.


Assuntos
Neurite do Plexo Braquial/diagnóstico , Neurite do Plexo Braquial/patologia , Neurite do Plexo Braquial/cirurgia , Diagnóstico Diferencial , Humanos , Nervos Periféricos/patologia , Nervos Periféricos/cirurgia
9.
Ther Umsch ; 77(6): 281-286, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32930076

RESUMO

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


Assuntos
Neuralgia/diagnóstico , Neuralgia/etiologia , Cirurgiões , Humanos , Doença Iatrogênica , Nervos Periféricos
10.
Artif Organs ; 43(2): 109-118, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30653695

RESUMO

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


Assuntos
Membros Artificiais , Biônica , Mãos , Desenho de Prótese , Humanos
11.
J Neuroeng Rehabil ; 16(1): 47, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953528

RESUMO

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


Assuntos
Algoritmos , Membros Artificiais , Eletromiografia/métodos , Processamento de Sinais Assistido por Computador , Articulação do Punho/fisiologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Movimento/fisiologia
12.
J Neuroeng Rehabil ; 16(1): 49, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975158

RESUMO

BACKGROUND: Replacement of a lost limb by an artificial substitute is not yet ideal. Resolution and coordination of motor control approximating that of a biological limb could dramatically improve the functionality of prosthetic devices, and thus reduce the gap towards a suitable limb replacement. METHODS: In this study, we investigated the control resolution and coordination exhibited by subjects with transhumeral amputation who were implanted with epimysial electrodes and an osseointegrated interface that provides bidirectional communication in addition to skeletal attachment (e-OPRA Implant System). We assessed control resolution and coordination in the context of routine and delicate grasping using the Pick and Lift and the Virtual Eggs Tests. Performance when utilizing implanted electrodes was compared with the standard-of-care technology for myoelectric prostheses, namely surface electrodes. RESULTS: Results showed that implanted electrodes provide superior controllability over the prosthetic terminal device compared to conventional surface electrodes. Significant improvements were found in the control of the grip force and its reliability during object transfer. However, these improvements failed to increase motor coordination, and surprisingly decreased the temporal correlation between grip and load forces observed with surface electrodes. We found that despite being more functional and reliable, prosthetic control via implanted electrodes still depended highly on visual feedback. CONCLUSIONS: Our findings indicate that incidental sensory feedback (visual, auditory, and osseoperceptive in this case) is insufficient for restoring natural grasp behavior in amputees, and support the idea that supplemental tactile sensory feedback is needed to learn and maintain the motor tasks internal model, which could ultimately restore natural grasp behavior in subjects using prosthetic hands.


Assuntos
Membros Artificiais , Eletrodos Implantados , Desempenho Psicomotor/fisiologia , Amputados , Eletromiografia/instrumentação , Eletromiografia/métodos , Retroalimentação Sensorial , Feminino , Força da Mão , Humanos , Masculino , Reprodutibilidade dos Testes
13.
J Neurosci ; 37(46): 11285-11292, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-29054880

RESUMO

We compared the behavior of motor neurons innervating their physiological muscle targets with motor neurons from the same spinal segment whose axons were surgically redirected to remnant muscles (targeted muscle reinnervation). The objective was to assess whether motor neurons with nonphysiological innervation receive similar synaptic input and could be voluntary controlled as motor neurons with natural innervation. For this purpose, we acquired high-density EMG signals from the biceps brachii in 5 male transhumeral amputees who underwent targeted reinnervation of this muscle by the ulnar nerve and from the first dorsal interosseous muscle of 5 healthy individuals to investigate the natural innervation of the ulnar nerve. The same recordings were also performed from the biceps brachii muscle of additional 5 able-bodied individuals. The EMG signals were decomposed into discharges of motor unit action potentials. Motor neurons were progressively recruited for the full range of submaximal muscle activation in all conditions. Moreover, their discharge rate significantly increased from recruitment to target activation level in a similar way across the subject groups. Motor neurons across all subject groups received common synaptic input as identified by coherence analysis of their spike trains. However, the relative strength of common input in both the delta (0.5-5 Hz) and alpha (5-13 Hz) bands was significantly smaller for the surgically reinnervated motor neuron pool with respect to the corresponding physiologically innervated one. The results support the novel approach of motor neuron interfacing for prosthesis control and provide new insights into the role of afferent input on motor neuron activity.SIGNIFICANCE STATEMENT Targeted muscle reinnervation surgically redirects nerves that lost their target in the amputation into redundant muscles in the region of the stump. The study of the behavior of motor neurons following this surgery is needed for designing biologically inspired prosthetic control strategies. Moreover, targeted muscle reinnervation offers a human experimental framework for studying the control and behavior of motor neurons when changing their target innervated muscle fibers and sensory feedback. Here, we show that the control of motor neurons and their synaptic input, following reinnervation, was remarkably similar to that of the physiological innervation, although with reduced common drive at some frequencies. The results advance our knowledge on the role of sensory input in the generation of the neural drive to muscles and provide the basis for designing physiologically inspired methods for prosthesis control.


Assuntos
Cotos de Amputação/inervação , Neurônios Motores/fisiologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Regeneração Nervosa/fisiologia , Sinapses/fisiologia , Potenciais de Ação/fisiologia , Adulto , Cotos de Amputação/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neurorretroalimentação/métodos , Neurorretroalimentação/fisiologia , Nervo Radial/fisiologia
14.
Ann Neurol ; 82(3): 396-408, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28833372

RESUMO

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


Assuntos
Braço/inervação , Axônios/fisiologia , Neurônios Motores/fisiologia , Células Receptoras Sensoriais/fisiologia , Colina O-Acetiltransferase/metabolismo , Humanos , Filamentos Intermediários/metabolismo , Células Receptoras Sensoriais/metabolismo
15.
Pediatr Blood Cancer ; 65(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28771999

RESUMO

PURPOSE: About 10% of patients with neurofibromatosis type 1 (NF-1) develop malignant peripheral nerve sheath tumours (MPNST) mostly arising in plexiform neurofibroma (PN); 15% of MPNST arise in children and adolescents. 2-[18 F]fluoro-2-deoxy-d-glucose ([18 F]FDG)-PET (where PET is positron emission tomography) is a sensitive method in differentiating PN and MPNST in symptomatic patients with NF-1. This study assesses the value of [18 F]FDG-PET imaging in detecting malignant transformation in symptomatic and asymptomatic children with PN. METHODS: Forty-one patients with NF-1 and extensive PN underwent prospective [18 F]FDG imaging from 2003 to 2014. Thirty-two of the patients were asymptomatic. PET data, together with histological results and clinical course were re-evaluated retrospectively. Maximum standardised uptake values (SUVmax) and lesion-to-liver ratio were assessed. RESULTS: A total of 104 examinations were performed. Mean age at first PET was 13.5 years (2.6-22.6). Eight patients had at least one malignant lesion; four of these patients were asymptomatic. Two of four symptomatic patients died, while all patients with asymptomatic malignant lesions are alive. All malignant tumours could be identified by PET imaging in both symptomatic and asymptomatic patients. All lesions judged as benign by [18 F]FDG imaging and clinical judgment were either histologically benign if removed or remained clinically silent during follow-up. SUVmax of malignant and benign lesions overlapped, but no malignant lesion showed FDG uptake ≤3.15. Asymptomatic malignant lesions were detected with a sensitivity of 100%, a negative predictive value of 100% and a specificity of 45.1%. CONCLUSION: Malignant transformation of PN also occurs in asymptomatic children and adolescents. Detection of MPNST at early stages could increase the possibility of oncologically curative resections.


Assuntos
Fluordesoxiglucose F18/administração & dosagem , Neurofibroma Plexiforme/diagnóstico por imagem , Neurofibromatose 1/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino
16.
Arthroscopy ; 34(10): 2874-2883, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30181057

RESUMO

PURPOSE: To (1) confirm the correct identification of the infrapatellar branches of the saphenous nerve (IPBSNs) by high-resolution ultrasound (HRUS) with ink marking and consecutive dissection in anatomic specimens; (2) evaluate the origin, course, and end-branch distribution in healthy volunteers; and (3) visualize the variable anatomic course of the IPBSN by HRUS. METHODS: HRUS with high-frequency probes (15-22 MHz) was used to locate the IPBSN in 14 fresh anatomic specimens at 4 different locations. The correct identification of the IPBSN was verified by ink marking and consecutive dissection. Moreover, the IPBSNs were located in both knees of 20 healthy volunteers (n = 40). Their courses were marked on the volunteers' skin in a flexed-knee position. Distances were measured from the IPBSN branch closest to the median of the patella base (D1), center (D2), and apex (D3) and in a 45° (D4) and 0° (D5) relation to the median patella apex. Standardized photographs of all knees were mapped on 1 typically shaped knee. RESULTS: Dissection confirmed the correct identification of the IPBSN in 86% to 100% of branches, depending on their location. Intraindividual differences for distance measurements were observed for D1 (P < .001) and D2 (P = .002). The coefficient of variation was highest for D5 (0.86) and lowest for D1 (0.14). Mapping of the nerve branches on a typical knee showed a highly variable course for the IPBSN. CONCLUSIONS: This study confirmed the reliable ability to visualize the IPBSN and its variations with HRUS in anatomic specimens and in healthy volunteers; such visualization may therefore enhance the diagnostic and therapeutic management of patients with anteromedial knee pain. CLINICAL RELEVANCE: Ultrasound successfully pinpoints the variable course of the IPBSN from the origin to the most distal point and, therefore, may enable the correct identification of (iatrogenic) nerve damage in every location.


Assuntos
Rede Nervosa/diagnóstico por imagem , Patela/inervação , Ultrassonografia/métodos , Adulto , Feminino , Humanos , Articulação do Joelho/inervação , Masculino , Dor/diagnóstico , Patela/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/diagnóstico , Estudos Prospectivos , Adulto Jovem
18.
Pain Pract ; 18(6): 709-715, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29105971

RESUMO

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


Assuntos
Membro Fantasma/prevenção & controle , Estimulação Física/métodos , Adulto , Amputação Cirúrgica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida
19.
Lancet ; 385(9983): 2183-9, 2015 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-25724529

RESUMO

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


Assuntos
Membros Artificiais , Biônica/métodos , Neuropatias do Plexo Braquial/reabilitação , Plexo Braquial/lesões , Procedimentos de Cirurgia Plástica/métodos , Recuperação de Função Fisiológica/fisiologia , Adulto , Amputação Cirúrgica , Eletromiografia , Mãos/fisiologia , Humanos , Masculino , Músculo Esquelético/fisiologia , Resultado do Tratamento
20.
Muscle Nerve ; 54(2): 292-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26788932

RESUMO

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


Assuntos
Fibras Musculares Esqueléticas/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Animais , Diagnóstico por Computador , Diagnóstico por Imagem , Imuno-Histoquímica , Masculino , Cadeias Pesadas de Miosina/classificação , Ratos , Ratos Sprague-Dawley , Análise de Regressão
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