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JOURNAL/nrgr/04.03/01300535-202506000-00029/figure1/v/2024-08-05T133530Z/r/image-tiff Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits (tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects (typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk+ tNGCs with the tubes without holes (silk- tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk+ tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk+ group was found compared with autologous nerve transplants and silk-, accompanied by improved axon regeneration at the distal coaptation point compared with the silk- tNGCs at 7 weeks postoperatively. In the 15-mm (critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk+ tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk+ tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

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A 71-year-old man who had hip abductor insufficiency due to a chronic injury to the right superior gluteal nerve injury after lipoma resection presented to our outpatient clinic 1.5 years postoperatively with persistent pain, atrophy of the gluteus medius muscle, and Trendelenburg sign with a corresponding limp. A magnetic resonance imaging scan and neurophysiological diagnostics confirmed a chronic lesion of the superior gluteal nerve with completed reinnervation and absent pathological spontaneous activity, excluding neurosurgical options to restore hip abduction. Following interdisciplinary evaluation of the patient's case, we performed a vastus lateralis transfer in May 2023 to stabilize the right hip joint. The entire vastus lateralis muscle was carefully freed from the surrounding tissue, and its attachment to the quadriceps tendon was separated. The proximal section of the lateral vastus was then fixed to the ilium and greater trochanter, while the muscle's distal portion was sutured to a more proximal part of the quadriceps muscle. The postoperative course was without any complications, and the patient left the hospital with an abduction splint 10 days after surgery. When he presented to our outpatient clinic 10 weeks after surgery, he reported a significantly improved gait and reduction of pain. Trendelenburg sign was now absent, but right knee function was not impaired and the patient was able to ambulate without the regular need for an orthosis. A transfer of the vastus lateralis muscle is therefore a valuable option to restore hip abductor function in cases of chronic nerve lesions which exclude neurosurgical options.

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Surgical techniques in amputation medicine did not change for a long time, while prosthesis technology underwent rapid development. The focus shifted to optimising the residual limb for prostheses use. At the same time, digital technologies such as gamification, virtual and mixed reality revolutionised rehabilitation. The use of gamification elements increases motivation and adherence to therapy, while immersive technologies enable realistic and interactive therapy experiences. This is particularly useful in the context of controlling modern prostheses and treating phantom pain. In addition, digital applications contribute to optimised documentation of symptoms and therapy successes. Overall, these technologies open up new, effective and personalised therapeutic approaches that can significantly improve the quality of life of amputation patients.

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Introduction Managing open lower extremity fractures is challenging, with potential complications such as amputation and infection. The aim of the study was to determine whether the time delay and initial treatment of the patients treated in a non-specialized hospital before being transferred to a dedicated level I trauma center led to a worse outcome. Methods Retrospective data from 44 patients (37 males and seven females) undergoing free tissue transfer for lower extremity open fractures from January 2017 to December 2022 were analyzed. Group A received primary care externally and was later transferred for definitive treatment (n=17, 38.6%), while group B received initial care at a level I trauma center (n=27, 61.4%). Surgical outcomes, complications, the duration of the hospital stay, and assessment times were compared. Various demographic variables, co-morbidities, prior interventions, and flap types were analyzed.  Results Average age (A: 55.1±16.7; B: 38.7±19.8 years; p=0.041), overall hospitalization (A: 55.7±22.8; B: 42.8±21.3 days; p=0.041), and time to soft tissue reconstruction differed significantly between groups (A: 30.7±12.2; B: 18.9±9.3 days; p=0.013). Overall, 31.8% had multiple injuries without statistical differences between groups A and B (29.4% vs. 33.3%; p>0.05). There were no statistical differences between the groups in terms of major and minor complications and bone healing characteristics. Limb salvage was successful overall in 93.2% (A: 94.1%; B: 92.6%; P>0.05). Major complications occurred in 9.1%; three patients underwent major amputation (A: n=2; B: n=1). Minor complications were observed in 43.2% of patients (partial flap necrosis, wound dehiscence and non-union; A: 41.2%; B: 44.4%; p>0.05). Overall, 65.9% of patients (A: 64.7%; B: 66.7%; p>0.05) experienced uneventful bone healing, while 18.2% of patients (A: 23.5%; B: 14.8%; p>0.05) experienced delayed healing. Flaps used were mostly musculocutaneous (71.7%). Various assessed demographic characteristics, including age and presence of polytrauma, showed no significant influence on complications (p>0.05). Conclusion  Although there is a significant difference in the time course of externally treated patients with open fractures, prolonged treatment is not associated with a higher complication rate or compromised bone healing outcome. Despite the findings, it is important to avoid delays and strive for interdisciplinary collaboration.

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BACKGROUND: The versatile musculocutaneous latissimus dorsi flap and the thoracodorsal artery (TDA) perforator flap have developed into indispensable approaches in reconstructive surgery. While the anatomy of the TDA is consistent, the skin perforators vary in location and course. Dynamic infrared thermography (DIRT) recently gained popularity for perforator identification; however, its use and accuracy in thoracodorsal artery perforator (TDAP) mapping is yet to be determined. METHODS: TDAPs were visualized in 50 cases by DIRT. Based on the thermographic hotspots, the corresponding perforators were then identified by color duplex ultrasound (CDU) and handheld Doppler in a blinded fashion by two separate examiners. RESULTS: The midpoint of all perforator fascia passages was localized 99.7 mm caudal and 13.5 mm medial of the posterior axillary fold. The positive predictive value of perforator identification by dynamic infrared thermography was 86.5% and the correlating perforator fascia passage was 9.9 ± 5.8 mm from the hotspot midpoint, with a maximum of 29 mm. The positive predictive value of perforator identification by handheld Doppler was 95% and the signal was 7.2 ± 5.1 mm from the perforator fascia passage. CONCLUSION: DIRT precisely localizes TDAPs. The fusion with CDU combines both modalities' advantages. The combination with handheld Doppler is a fast way of perforator imaging, decreasing the handheld Dopplers' high false positive rate.

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BACKGROUND: The causes of spasticity are various and include cerebral palsy, spinal cord injury, stroke, multiple sclerosis or other congenital or acquired lesions of the central nervous system (CNS). While there is often a partial functional component, spasticity also results in varying degrees of impairment of the quality of life. OBJECTIVE: A review of surgical treatment options for spasticity. MATERIAL AND METHODS: A systematic PubMed review of the literature on epidemiology and treatment options with a focus on neurosurgical interventions for spasticity and developments in the last 20 years as well as inclusion of still valid older landmark papers was carried out. Illustration of indications, technique, follow-up, and possible pitfalls of the different methods for the surgical treatment of spasticity. RESULTS: Depending on the affected region, the number of muscle groups, and the extent of spasticity, focal (selective peripheral neurotomy, nerve transfer), regional (selective dorsal rhizotomy), or generalized (baclofen pump) procedures can be performed. The indications are usually established by an interdisciplinary team. Conservative (physiotherapy, oral medications) and focally invasive (botulinum toxin injections) methods should be performed in advance. In cases of insufficient response to treatment or only short-term relief, surgical methods can be evaluated. These are usually preceded by test phases with, for example, trial injections. CONCLUSION: Surgical methods are a useful adjunct in cases of insufficient response to conservative treatment in children and adults with spasticity.

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Arthritic disorders have become one of the main contributors to the global burden of disease. Today, they are one of the leading causes of chronic pain and disability worldwide. Current therapies are incapable of treating pain sufficiently and preventing disease progression. The lack of understanding basic mechanisms underlying the initiation, maintenance and progression of arthritic disorders and related symptoms represent the major obstacle in the search for adequate treatments. For a long time, histological evaluation of joint pathology was the predominant outcome parameter in preclinical arthritis models. Nevertheless, quantification of pain and functional limitations analogs to arthritis related symptoms in humans is essential to enable bench to bedside translation and to evaluate the effectiveness of new treatment strategies. As the experience of pain and functional deficits are often associated with altered gait behavior, in the last decades, automated gait analysis has become a well-established tool for the quantitative evaluation of the sequalae of arthritic disorders in animal models. The purpose of this review is to provide a detailed overview on the current literature on the use of the CatWalk gait analysis system in rodent models of arthritic disorders, e.g., Osteoarthritis, Monoarthritis and Rheumatoid Arthritis. Special focus is put on the assessment and monitoring of pain-related behavior during the course of the disease. The capability of evaluating the effect of distinct treatment strategies and the future potential for the application of the CatWalk in rodent models of arthritic disorders is also addressed in this review. Finally, we discuss important consideration and provide recommendations on the use of the CatWalk in preclinical models of arthritic diseases.

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BACKGROUND: The functional deficits that develop after a peripheral nerve injury mean a considerable reduction in the quality of life for the affected patients. However, interventions on the injured nerve are not always possible or effective. In this case, secondary procedures, e.g. tendon transfers, are a feasible option for functional reconstruction. OBJECTIVES: An overview of the most common secondary surgical procedures for functional reconstruction after peripheral nerve injuries. METHODS: Presentation and discussion of the most common secondary surgical procedures with emphasis on tendon transfers. Illustration of the primary functions that need to be reconstructed depending on the respective nerve lesion. RESULTS: The basic principle of secondary surgical procedures after nerve injuries is the transposition of a healthy tendomuscular unit to replace a lost function following a loss of muscle or tendon or if an intervention on the nerve is not promising. For example, by transferring flexor forearm muscles, wrist, finger and thumb extension can be reconstructed after radial nerve injury. By transposing the tibialis posterior muscle, dorsiflexion in the talocrural joint can be restored to enable the affected patient to walk safely without an orthosis. CONCLUSIONS: Secondary surgical procedures are a valuable option for functional reconstruction after nerve injury.

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BACKGROUND: Facial aesthetics are of great importance in social interaction. With the widespread adoption of face masks in response to the Covid-19 pandemic, there is growing interest in understanding how wearing masks might impact perceptions of attractiveness, as they partially or completely conceal facial features that are typically associated with attractiveness. OBJECTIVES: This study aimed to explore the impact of mask wearing on attractiveness and to investigate whether the color (red or blue) of the mask has any effect on the perception of a person's attractiveness, while also considering gender and age as contributing factors. Additionally, the study intended to evaluate gaze patterns, initial focus, and dwell time in response to masked and unmasked faces. METHODS: 30 AI-generated images of 15 female and 15 male faces were presented to 71 participants (35 male, 36 female) in 3 conditions: not wearing any mask, wearing a red surgical mask, and wearing a blue surgical mask. The perceived attractiveness was rated on an ordinal scale of 1-10 (10 being most attractive). Gaze behavior, dwell time and initial focus were recorded using a stationary eye-tracking system. RESULTS: The study found that wearing masks had no significant effect on the attractiveness ratings of female faces (p = .084), but it did benefit the perceived attractiveness of male faces which were initially rated lower (p = .16). Gender and age also played a significant role, as both male and female participants rated female stimuli higher than male stimuli (p < .001), and younger participants rated both genders as less attractive than older participants (p < .01). However, there was no significant influence of the mask's color on attractiveness. During the eye-tracking analysis, the periorbital region was of greater interest while masked, with the time to first fixation for the eyes being lower than the non-masked stimulus (p < .001) and showed a longer dwell time (p < .001). The lower face was shown less interest while masked as the time to first fixation was higher (p < .001) and the fixation count was less (p < .001). Mask color did not influence the scan path and there was no difference in revisits to the mask area between red or blue masks (p = .202), nor was there a difference in time to first fixation (p = .660). CONCLUSIONS: The study findings indicate that there is an interplay between the gender and age of the participant and the facial stimuli. The color red did have an effect on the perception attractiveness, however not in female faces. The results suggest that masks, especially red ones, might be more beneficial for male faces, which were perceived as less attractive without a mask. However, wearing a mask did not significantly impact already attractive faces. The eye-tracking results revealed that the periorbital region attracted more attention and was fixated on more quickly while wearing a mask, indicating the importance of eyes in social interaction and aesthetic perception.

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Sleep deprivation is known to have serious consequences, including a decrease in performance, attention and neurocognitive function. It seems common knowledge that medical residents are routinely sleep deprived, yet there is little objective research recording their average sleep times. To discern whether residents may be suffering from the abovementioned side effects, this review aimed to analyze their average sleep times. Thirty papers recording the average sleep time of medical residents were found via a literature search using the key words "resident" and "sleep". An analysis of the mean sleep times cited therein revealed a range of sleep from 4.2 to 8.6 h per night, the median being 6.2 h. A sub-analysis of papers from the USA showed barely any significant differences in sleep time between the specialties, but the mean sleep times were below 7 h. The only significant difference (p = 0.039) was between the mean sleep times of pediatric and urology residents, with the former achieving less sleep. The comparison of methods for data collection showed no significant difference in the sleep times collected. The results of this analysis imply that residents are regularly sleep deprived and may therefore suffer from the abovementioned consequences.

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PURPOSE: Muscle-in-vein conduits provide an alternative for bridging digital nerve defects when tension-free suture is not possible. Low donor site morbidity and absence of additional costs are favorable advantages compared with autografts or conduits. METHODS: We retrospectively reviewed 37 patients with 43 defects of proper palmar digital nerves. Primary repair by muscle-in-vein conduits was performed in 22 cases, whereas 21 cases underwent secondary reconstruction. Recovery of sensibility was assessed using static and moving 2-point discrimination and Semmes-Weinstein monofilament testing. Results were compared with the contralateral side serving as a control. Outcome data were stratified according to international guidelines and evaluated for differences in terms of age, gap length, time of reconstruction, and concomitant injuries. RESULTS: The median gap length was 20 mm (range, 9-60 mm). After a median follow-up of 25.0 months (interquartile range, 29.0 months), the median static and moving 2-point discrimination were 7.0 mm and 5.0 mm (interquartile range, 3.0 mm), respectively. The evaluation with Semmes-Weinstein monofilament revealed a median reduction of sensibility of 2 levels compared with the contralateral side. According to the American Society for Surgery of the Hand guidelines, 81.4% of the results were classified as excellent or good, whereas fair and poor results were noted in 9.3% of the cases each. The modified Highet and Sander's criteria rated complete clinical recovery in 13 cases; 23 results were regarded as S3+. CONCLUSIONS: Muscle-in-vein conduits can be considered for primary and secondary reconstruction of digital nerves. Successful sensory recovery in terms of measurable 2-point discrimination was achieved in 91% of all cases. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

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AIM: Peripheral nerve tumors (PNT) are rare lesions. To date, no systematic multicenter studies on epidemiology, clinical symptoms, treatment strategies and outcomes, genetic and histopathologic features, as well as imaging characteristics of PNT were published. The main goal of our PNT Registry is the systematic multicenter investigation to improve our understanding of PNT and to assist future interventional studies in establishing hypotheses, determining potential endpoints, and assessing treatment efficacy. METHODS: Aims of the PNT registry were set at the 2015 Meeting of the Section of Peripheral Nerve Surgery of the German Society of Neurosurgery. A study protocol was developed by specialists in PNT care. A minimal data set on clinical status, treatment types and outcomes is reported by each participating center at initial contact with the patient and after 1 year, 2 years, and 5 years. Since the study is coordinated by the Charité Berlin, the PNR Registry was approved by the Charité ethics committee (EA4/058/17) and registered with the German Trials Registry (www.drks.de). On a national level, patient inclusion began in June 2016. The registry was rolled out across Europe at the 2019 meeting of the European Association of Neurosurgery in Dublin. RESULTS: Patient recruitment has been initiated at 10 centers throughout Europe and 14 additional centers are currently applying for local ethics approval. CONCLUSION: To date, the PNT registry has grown into an international study group with regular scientific and clinical exchange awaiting the first results of the retrospective study arm.

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Currently, there is neither a standardized mode for the documentation of phantom sensations and phantom limb pain, nor for their visualization as perceived by patients. We have therefore created a tool that allows for both, as well as for the quantification of the patient's visible and invisible body image. A first version provides the principal functions: (1) Adapting a 3D avatar for self-identification of the patient; (2) modeling the shape of the phantom limb; (3) adjusting the position of the phantom limb; (4) drawing pain and cramps directly onto the avatar; and (5) quantifying their respective intensities. Our tool (C.A.L.A.) was evaluated with 33 occupational therapists, physiotherapists, and other medical staff. Participants were presented with two cases in which the appearance and the position of the phantom had to be modeled and pain and cramps had to be drawn. The usability of the software was evaluated using the System Usability Scale and its functional range was evaluated using a self-developed questionnaire and semi-structured interview. In addition, our tool was evaluated on 22 patients with limb amputations. For each patient, body image as well as phantom sensation and pain were modeled to evaluate the software's functional scope. The accuracy of the created body image was evaluated using a self-developed questionnaire and semi-structured interview. Additionally, pain sensation was assessed using the SF-McGill Pain Questionnaire. The System Usability Scale reached a level of 81%, indicating high usability. Observing the participants, though, identified several operational difficulties. While the provided functions were considered useful by most participants, the semi-structured interviews revealed the need for an improved pain documentation component. In conclusion, our tool allows for an accurate visualization of phantom limbs and phantom limb sensations. It can be used as both a descriptive and quantitative documentation tool for analyzing and monitoring phantom limbs. Thus, it can help to bridge the gap between the therapist's conception and the patient's perception. Based on the collected requirements, an improved version with extended functionality will be developed.

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The rat median nerve model is a well-established and frequently used model for peripheral nerve injury and repair. The grasping test is the gold-standard to evaluate functional recovery in this model. However, no comprehensive review exists to summarize the course of functional recovery in regard to the lesion type. According to PRISMA-guidelines, research was performed, including the databases PubMed and Web of Science. Groups were: (1) crush injury, (2) transection with end-to-end or with (3) end-to-side coaptation and (4) isogenic or acellular allogenic grafting. Total and respective number, as well as rat strain, type of nerve defect, length of isogenic or acellular allogenic allografts, time at first signs of motor recovery (FSR) and maximal recovery grasping strength (MRGS), were evaluated. In total, 47 articles met the inclusion criteria. Group I showed earliest signs of motor recovery. Slow recovery was observable in group III and in graft length above 25 mm. Isografts recovered faster compared to other grafts. The onset and course of recovery is heavily dependent from the type of nerve injury. The grasping test should be used complementary in addition to other volitional and non-volitional tests. Repetitive examinations should be planned carefully to optimize assessment of valid and reliable data.

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Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT-applied within the subacute and chronic phase of SCI (spinal cord injury) on recovery in a rat spinal cord contusion model. Outcomes were evaluated by gait analysis, µCT and histological analysis of spinal cords. A panel of serum-derived miRNAs after SCI and after ESWT was investigated to identify injury-, regeneration- and treatment-associated expression patterns. Rats receiving ESWT showed significant improvement in motor function in both a subacute and a chronic experimental setting. This effect was not reflected in changes in morphology, µCT-parameters or histological markers after ESWT. Expression analysis of various miRNAs, however, revealed changes after SCI and ESWT, with increased miR-375, indicating a neuroprotective effect, and decreased miR-382-5p potentially improving neuroplasticity via its regulatory involvement with BDNF. We were able to demonstrate a functional improvement of ESWT-treated animals after SCI in a subacute and chronic setting. Furthermore, the identification of miR-375 and miR-382-5p could potentially provide new targets for therapeutic intervention in future studies.

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Investigations reporting positive effects of extracorporeal shockwave therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7 mm segment of the right median nerve was reconstructed either with an ANG or an MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. The animals were observed for 12 weeks, and nerve regeneration was assessed using computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here, we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair.

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Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in cases of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly under-investigated. In this study, we analyzed the presence of lymphatic vasculature in healthy and regenerated murine peripheral nerves, revealing that nerve autografts contained increased numbers of lymphatic vessels after segmental damage. This led us to elucidate the interaction between lymphatic endothelial cells (LECs) and Schwann cells (SCs) in vitro. We show that SC and LEC secretomes did not influence the respective other cell types' migration and proliferation in 2D scratch assay experiments. Furthermore, we successfully created lymphatic microvascular structures in SC-embedded 3D fibrin hydrogels, in the presence of supporting cells; whereas SCs seemed to exert anti-lymphangiogenic effects when cultured with LECs alone. Here, we describe, for the first time, increased lymphangiogenesis after peripheral nerve injury and repair. Furthermore, our findings indicate a potential lymph-repellent property of SCs, thereby providing a possible explanation for the lack of lymphatic vessels in the healthy endoneurium. Our results highlight the importance of elucidating the molecular mechanisms of SC-LEC interaction.

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We report the case of a 62-year-old female patient with a triple-crush radial nerve injury, diagnosed in subsequent order following a fracture of the left humerus. The patient developed flaccid paralysis of all muscles innervated by the left radial nerve except the triceps brachii and reported a sensory deficit corresponding to the innervation territories of the posterior nerve of the forearm as well as the superficial branch of the radial nerve. Following neurolysis of the radial nerve at the humerus level, wrist extension as well as sensory perception on the dorsal aspect of the forearm recovered, but finger extension and thumb abduction were still impossible. Following neurological evaluation and nerve ultrasound, supinator syndrome was diagnosed and the patient underwent decompression surgery. Following surgical decompression, motor recovery was observable but a sensory deficit remained in the area innervated by the superficial branch of the radial nerve. In consequence, the third crush injury of the left radial nerve, that is, Wartenberg syndrome or cheiralgia paraesthetica was diagnosed. Decompression surgery of the superficial branch of the radial nerve was performed and the patient reported profound amelioration of her sensory symptoms during a follow-up examination at our outpatient clinic 6 weeks postoperatively.

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Peripheral nerve injuries are a common clinical problem. They not only affect the physical capabilities of the injured person due to loss of motor or sensory function but also have a significant impact on psychosocial aspects of life. The aim of this work is to review the interplay of psychosocial factors and peripheral nerve lesions. By reviewing the published literature, we identified several factors to be heavily influenced by peripheral nerve lesions. In addition to psychological factors like pain, depression, catastrophizing and stress, social factors like employment status and worker's compensation status could be identified to be influenced by peripheral nerve lesions as well as serving as predictors of functional outcome themselves, respectively. This work sheds a light not only on the impact of peripheral nerve lesions on psychosocial aspects of life, but also on the prognostic values of these factors of functional outcome. Interdisciplinary, individualized treatment of patients is required to identify patient at risk for adverse outcomes and provide them with emotional support when adapting to their new life situation.

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The gold-standard method for reconstruction of segmental nerve defects, the autologous nerve graft, has several drawbacks in terms of tissue availability and donor site morbidity. Therefore, feasible alternatives to autologous nerve grafts are sought. Muscle-in-vein conduits have been proposed as an alternative to autologous nerve grafts almost three decades ago, given the abundance of both tissues throughout the body. Based on the anti-inflammatory effects of veins and the proregenerative environment established by muscle tissue, this approach has been studied in various preclinical and some clinical trials. There is still no comprehensive systematic summary to conclude efficacy and feasibility of muscle-in-vein conduits for reconstruction of segmental nerve defects. Given this lack of a conclusive summary, we performed a meta-analysis to evaluate the potential of muscle-in-vein conduits. This work's main findings are profound discrepancies regarding the results following nerve repair by means of muscle-in-vein conduits in a preclinical or clinical setting. We identified differences in study methodology, inter-species neurobiology and the limited number of clinical studies to be the main reasons for the still inconclusive results. In conclusion, we advise for large animal studies to elucidate the feasibility of muscle-in-vein conduits for repair of segmental defects of critical size in mixed nerves.

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