Muscle Reinnervation Research Articles

Targeted Muscle Reinnervation of the Supraclavicular Nerve to the Motor Branch of the Omohyoid Muscle in Patients Undergoing Thoracic Outlet Syndrome Procedures.

Summary:Transection of the supraclavicular nerve (SCN) through supraclavicular incisions can lead to debilitating neuroma formation. Targeted muscle reinnervation (TMR) proved to be an effective technique for the prevention and treatment of neuroma. In this case series, we propose the TMR of the SCN to the motor branch of the omohyoid muscle (OM) to prevent the formation of neuroma and avoid chronic pain at the supraclavicular area after thoracic outlet syndrome (TOS) procedures. A total of 10 patients underwent the procedure. Dissection of the SCN and its branches was performed through a supraclavicular incision. The branches were transected close to the clavicle. The inferior belly of the OM was identified and its motor branch isolated. Coaptation of the SCN branches with the motor branch of the OM was performed under the microscope and the wound was closed in layers. All the patients denied pain or hypersensitivity at the supraclavicular area on follow-up. In summary, the motor branch of the OM is a viable recipient for the TMR of the SCN and can prevent and treat painful neuromas at the supraclavicular area with minimal morbidity.

Impact of Timing of Targeted Muscle Reinnervation on Pain and Opioid Intake Following Major Limb Amputation.

Targeted muscle reinnervation (TMR) has been shown to play an important role in managing neuromas. However, the impact of the timing of TMR on pain visual analogue scale (VAS) scores or patient opioid use has not been thoroughly explored. We hypothesized that TMR performed acutely would lead to lower VAS scores and decreased opioid intake. Prospectively collected data from an amputation registry at a single institution were utilized to identify patients who underwent TMR. Acute TMR was defined as TMR performed within 1 month of the major limb amputation. Primary outcomes included VAS pain scores and patient-reported opioid consumption. In all, 25 patients (26 limbs) were identified in the acute group, and 18 patients (18 limbs) were identified in the delayed group. At intermediate follow-up (between 4 and 8 months postoperatively) and at final follow-up, the average pain VAS score in the delayed TMR group was significantly higher than that in the acute group (5.2 vs. 1.9 at intermediate P = .01 and 6.2 vs. 1.9 at final P = .002). In all, 84% of the amputees overall were not consuming opioid medications at the time of final follow-up (79% acute, 88% delayed, P = .72). There were no statistically significant differences in opioid consumption between the acute and delayed group at intermediate follow-up (P = .35) or at final follow-up (P = .68). TMR is an effective procedure to reduce pain following major limb amputation. Patients with TMR performed acutely had significantly lower VAS pain scores at both intermediate and final follow-up than patients with TMR performed in a delayed setting. Therapeutic II.

Primary Targeted Muscle Reinnervation after Below-Knee Amputation Is Not Associated with an Increased Risk of Major or Minor Surgical Complications: A Multi-Institutional, Propensity Score-Matched Analysis.

Targeted muscle reinnervation has emerged as a technique to reduce neuroma and phantom limb pain after below-knee amputation; however, the incidence of postoperative complications remains unknown. This multi-institutional study assessed the risk of postoperative complications among patients who underwent targeted muscle reinnervation at the time of below-knee amputation. Patients who underwent below-knee amputation with targeted muscle reinnervation were propensity score-matched 1:3 to patients who underwent below-knee amputation alone. Study outcomes included the incidence of major or minor complications within 60 days. Regression models were used to estimate the relative risk of major and minor complications. Overall, 96 patients were matched, including 31 patients who had below-knee amputation with targeted muscle reinnervation and 65 who had below-knee amputation alone. In the matched sample, a higher incidence of major complications (29 percent versus 24.6 percent), readmission (25.8 percent versus 18.5 percent), and reoperation (19.4 percent versus 10.8 percent) was seen after both procedures compared with below-knee amputation alone. Patients who underwent both procedures displayed a higher incidence of minor complications (25.8 percent versus 20.0 percent), blood transfusion (22.6 percent versus 18.5 percent), and wound healing complications (45.2 percent versus 33.8 percent) and longer operative time (mean ± SD, 188.5 ± 63.6 minutes versus 88 ± 28.2 minutes). There was no statistically significant difference in the risk of major (relative risk, 1.20; 90 percent CI, 0.68, 2.11) or minor (relative risk, 1.21; 90 percent CI, 0.61, 2.41) complications between the two cohorts. Despite an increased incidence of postoperative complications, undergoing below-knee amputation with targeted muscle reinnervation does not confer a statistically significant increased risk of major or minor complications. Future studies are needed to delineate patient selection criteria when assessing the suitability of targeted muscle reinnervation at the time of major limb amputation. Therapeutic, III.

Use of Vascularized, Denervated Muscle Targets for Prevention and Treatment of Upper-Extremity Neuromas

Neuroma formation following upper-extremity peripheral nerve injury often results in persistent, debilitating neuropathic pain with a limited response to medical management. Vascularized, denervated muscle targets (VDMTs) offer a newly described surgical approach to address this challenging problem. Like targeted muscle reinnervation and regenerative peripheral nerve targets, VDMTs are used to redirect regenerating axons from an injured nerve into denervated muscle to prevent neuroma formation. By providing a vascularized muscle target that is reinnervated via direct neurotization, VDMTs offer some theoretical advantages in comparison with the other contemporary surgical options. In this study, we followed the short-term pain outcomes of patients who underwent VDMT surgery for neuroma prevention or treatment. We performed a retrospective chart review of 9 patients (2 pediatric and 7 adult) who underwent VDMTs either for symptomatic upper-extremity neuromas or as a prophylactic measure to prevent primary neuroma formation. In-person and/or telephone interviews were conducted to assess their postoperative clinical outcomes, including the visual analog pain scale simple pain score. Of the 9 patients included in this study, 7 underwent VDMT surgery as a prophylactic measure against neuroma formation, and 2 presented with symptomatic neuromas that were treated with VDMTs. The average follow-up was 5.6 ± 4.1 months (range, 0.5-13.2 months). The average postoperative pain score of the 7 adult patients was 1.1 (range, 0-8). This study demonstrated favorable short-term outcomes in a small cohort of patients treated with VDMTs in the upper extremity. Larger, prospective, and comparative studies with validated patient-reported and objective outcome measures and longer-term follow-ups are needed to further evaluate the benefits of VDMTs in upper-extremity neuroma management and prevention. Therapeutic III.

Sensory nerve regeneration and reinnervation in muscle following peripheral nerve injury.

Sensory afferent fibers are an important component of motor nerves and compose the majority of axons in many nerves traditionally thought of as "pure" motor nerves. These sensory afferent fibers innervate special sensory end organs in muscle, including muscle spindles that respond to changes in muscle length and Golgi tendons that detect muscle tension. Both play a major role in proprioception, sensorimotor extremity control feedback, and force regulation. After peripheral nerve injury, there is histological and electrophysiological evidence that sensory afferents can reinnervate muscle, including muscle that was not the nerve's original target. Reinnervation can occur after different nerve injury and muscle models, including muscle graft, crush, and transection injuries, and occurs in a nonspecific manner, allowing for cross-innervation to occur. Evidence of cross-innervation includes the following: muscle spindle and Golgi tendon afferent-receptor mismatch, vagal sensory fiber reinnervation of muscle, and cutaneous afferent reinnervation of muscle spindle or Golgi tendons. There are several notable clinical applications of sensory reinnervation and cross-reinnervation of muscle, including restoration of optimal motor control after peripheral nerve repair, flap sensation, sensory protection of denervated muscle, neuroma treatment and prevention, and facilitation of prosthetic sensorimotor control. This review focuses on sensory nerve regeneration and reinnervation in muscle, and the clinical applications of this phenomena. Understanding the physiology and limitations of sensory nerve regeneration and reinnervation in muscle may ultimately facilitate improvement of its clinical applications.

Feasibility Study on Disentangling Muscle Movements in TMR Patients Through a Myokinetic Control Interface for the Control of Artificial Hands

Targeted muscle reinnervation (TMR) is a surgical procedure which allows to restore myoelectric control sources in people with proximal upper-limb amputations. However, the large physical displacement generally provoked by the reinnervated muscles following contraction can represent a drawback for the use of surface electrodes, which are affected by movement artifacts. In this regard, the viability of directly exploiting the physical displacement of muscles as control source would be beneficial. We recently introduced the so called <i>myokinetic interface</i>, aimed at transducing muscle movements into decipherable signals for artificial hands by tracking magnetic markers implanted inside the muscles. This work features the combination of the TMR procedure with such interface, in a non-invasive way. Two participants who underwent TMR surgery following above-the-elbow amputation were enrolled in this study. During two experimental sessions, we assessed the feasibility of: (i) disentangling muscle displacements associated with different degrees of freedom (DoFs) of the missing limb through video analysis, and (ii) discriminating different DoFs by tracking the displacement of five magnetic markers placed on the skin, over the reinnervated sites. A simple logistic regressor proved able to discriminate three different DoFs (six movements), with an average F1-score among classes and testing conditions of 0.84 (0.65) and 0.69 (0.60) for the video and the myokinetic data, for the first (second) participant, respectively. The presented outcomes encourage further investigations, and pave the way towards novel control strategies for artificial hands in TMR patients.

102. Novel Methodology for Systematic Sensory Characterization and Stimulus Testing After Major Limb Loss

Purpose: Sensory referral is commonly experienced by patients after amputation, in which touches to the residual limb are perceived as originating from the phantom limb. This phenomenon offers a compelling interface for noninvasive delivery of sensory feedback in prosthetic limbs. However, a more comprehensive understanding of the complexities of the sensory experience is necessary, especially with the rising popularity of surgical techniques such as targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI). We hypothesize that in TMR and RPNI, repurposing and providing transected nerves with muscle targets for reinnervation may alter or induce patterns of referred sensation. Methods: To study this, we have developed a novel methodology for detailed sensory characterization of the residual limb, compatible for both upper and lower extremity amputation. We designed a computer program for mapping sensory referral, in which participants interact with a virtual representation of their phantom limb. With a touchscreen laptop, participants can zoom and rotate to see the entire limb. Light touch, deep pressure, and vibratory stimuli are presented to the residual limb, and participants tap on the virtual limb to mark the location of the perceived sensation. Results: Our software interface is intuitive for participants to use and is designed to provide a standardized testing methodology, such that any researcher may quickly and confidently perform rigorous, repeatable sensory characterization of a limb. It also minimizes experimenter bias by eliminating ambiguity in verbal responses; participants tap directly on the virtual limb where the feeling appears to originate without needing to verbally describe that anatomical location. The data points on the virtual limb can then be correlated with the tested points on the residual limb to generate a map of referred sensation. Conclusion: Providing an egocentric virtual body for sensory testing enables participants to indicate with high accuracy where a stimulus is perceived on their phantom limb. With our innovative tool, we can screen for individuals with sensory referral and generate complete sensory referral mappings of the residual limb. Aspects of sensory capabilities can be compared across individuals and groups, including surface area of referring skin and rate of referral to peripheral nerve distributions or phantom limb anatomy. Our systematic methodology will facilitate unbiased explorations of sensory referral after amputation, especially after TMR and RPNI surgery.

Blood vessel remodeling in late stage of vascular network reconstruction is essential for peripheral nerve regeneration.

One of the bottlenecks of advanced study on tissue engineering in regenerative medicine is rapid and functional vascularization. For a deeper comprehension of vascularization, the exhaustive, dynamic, and three‐dimensional depiction of perfused vascular network reconstruction during peripheral nerve regeneration was performed using Micro‐CT scanning. The 10 mm defect of sciatic nerve in rat was bridged by the autologous or tissue engineered nerve. The blood vessel anastomosis between nerve stumps and autologous nerve accomplished at 4 days to 1 week after surgery, which was a sufficient basis for the mature vascular network re‐establishment. The stronger ability for sprouting angiogenesis and vascular remodeling of autologous nerve compared with tissue engineered nerve was revealed. However, common phases of vascularization in peripheral nerve regeneration were painted: hypoxic initiation, sprouting angiogenesis, and remodeling and maturation. The effect of less‐concerned vascular remodeling on nerve regeneration was further analyzed after nerve crush injury. The blockage of vascular remodeling in late stage by VEGF injection significantly inhibited axons and myelin sheaths regeneration, which attenuated the impulse conduction toward reinnervated muscles. It was illustrated that a large amount of immature blood vessels rather than necessary vascular remodeling elevated local inflammation level in nerve regeneration microenvironment. The figures inspired us to understand the close connections between vascularization and peripheral nerve regeneration from a broader dimension to achieve better constructions, regulations and repair effects of tissue engineered nerves in clinic.

Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces Versus Standard Management in the Treatment of Limb Amputation: A Systematic Review and Meta-Analysis.

Introduction: Painful neuromas are a common postoperative complication of limb amputation often treated with secondary reinnervation. Surgical reinnervation include Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), and can be primary and secondary. The aim of this review is to assess the effects of primary TMR/RPNI at the time of limb amputation on the incidence and intensity of post-operative neuroma and pain. Methods: This review was registered a priori on PROSPERO (CRD42021264360). A search of the following databases was performed in June 2021: Medline, EMBASE, and CENTRAL. Unpublished trials were searched using clinicaltrials.gov. All randomized and non-randomized studies assessing amputation with a reinnervation strategy (TMR, RPNI) were included. Outcomes evaluated included the incidences of painful neuroma, phantom limb pain (PLP), residual limb pain (RLP), as well as severity of pain, and Pain intensity, behavior, and interference (PROMIS). Results: Eleven studies were included in this systematic review, and five observational studies for quantitative synthesis. Observational study evidence suggests that TMR/RPNI results in a statistically significant reduction in incidence, pain scores and PROMIS scores of PLP and RLP. Decreased incidence of neuromas favored primary TMR/RPNI, but this did not achieve statistical significance (p = 0.07). Included studies had moderate to critical risk of bias. Conclusion: The observational data suggests that primary TMR/RPNI reduces incidence, pain scores and PROMIS scores of PLP and RLP. Going forward, randomized trials are warranted to evaluate this research question, particularly to improve the certainty of evidence.

Integrating Mechanisms of Exacerbated Atrophy and Other Adverse Skeletal Muscle Impact in COPD.

The normal decline in skeletal muscle mass that occurs with aging is exacerbated in patients with chronic obstructive pulmonary disease (COPD) and contributes to poor health outcomes, including a greater risk of death. There has been controversy about the causes of this exacerbated muscle atrophy, with considerable debate about the degree to which it reflects the very sedentary nature of COPD patients vs. being precipitated by various aspects of the COPD pathophysiology and its most frequent proximate cause, long-term smoking. Consistent with the latter view, recent evidence suggests that exacerbated aging muscle loss with COPD is likely initiated by decades of smoking-induced stress on the neuromuscular junction that predisposes patients to premature failure of muscle reinnervation capacity, accompanied by various alterations in mitochondrial function. Superimposed upon this are various aspects of COPD pathophysiology, such as hypercapnia, hypoxia, and inflammation, that can also contribute to muscle atrophy. This review will summarize the available knowledge concerning the mechanisms contributing to exacerbated aging muscle affect in COPD, consider the potential role of comorbidities using the specific example of chronic kidney disease, and identify emerging molecular mechanisms of muscle impairment, including mitochondrial permeability transition as a mechanism of muscle atrophy, and chronic activation of the aryl hydrocarbon receptor in driving COPD muscle pathophysiology.

Prospect of Stem Cells as Promising Therapy for Brachial Plexus Injury: A Systematic Review.

BackgroundBrachial plexus injury is an advanced and devastating neurological injury, for which both nerve surgery and tendon transfers sometimes remain insufficient in restoring normal movement. Stem cell therapy may be applicable to rescue the injured motor neurons from degeneration which potentially improves muscle strength.Study DesignSystematic Review; Level of evidence V.Data SourcesA systematic literature search was conducted on PubMed (MEDLINE), EMBASE, the Cochrane Library, and Scopus using the terms (“stem cell”) AND (“brachial plexus”) as search keywords.MethodsThe process of study selection was summarized by PRISMA flow diagram. The study included in vivo and in vitro studies with English language, humans or animals with some brachial plexus injuries, interventions, some applications of stem cells to the groups of study, with functional, biomechanical, or safety outcomes.ResultsIn total, there were 199 studies identified from the literature sources where 75 articles were qualified for forward evaluation following selecting the titles and abstracts. Ten studies were finally included in this systematic review after full-text assessment. Stem cells can produce neurotrophic factors in vitro and in vivo in rats, and their level was increased after injury. Electrophysiological measurement showed that the intervention group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than the model group. Application of bone marrow stem cells (BMSCs) showed an elevation in the numbers of axons and density of myelinated fibers, the density of nerve fibers, the diameter of regenerating axons, and a decrease in axonal degeneration. A study in humans indicated an improvement of the movements in a patient with traumatic total BPI after injection of Ad-MSC. It is associated with increased muscle mass and sensory recovery and also suggested that mononuclear cell injection enhances muscle regeneration and reinnervation in the partly denervated muscle of brachial plexus injury. Various muscle groups had obtained strength together with restoration, the muscle strength attained after the previous transplantation were preserved. The results of this review support stem cell treatment in brachial plexus injury.ConclusionThis review provides evidence of the positive effects of stem cell treatment in brachial plexus injury.

Targeted muscle reinnervation prevents and reverses rat pain behaviors after nerve transection.

Targeted muscle reinnervation (TMR) is a clinical intervention that is rapidly becoming common in major limb amputation to prevent or reduce amputation-related pain. However, TMR is much less effective when applied long after injury compared with acute TMR. Since the mechanisms governing pain relief in TMR of amputated nerves are unknown, we developed a preclinical model as a platform for mechanistic examination. Following spared nerve injury (SNI), rats underwent either TMR, simple neuroma excision, or a sham manipulation of the injury site. These interventions were performed immediately or delayed (3 or 12 weeks) after SNI. Pain behavior was measured as sensitivity to mechanical stimuli (pin, von Frey, and dynamic brush) and thermal stimuli (acetone and radiant heat). Spared nerve injury produced hypersensitivity to all mechanical stimuli and cold, which persisted after sham surgery. Targeted muscle reinnervation at the time of SNI prevented the development of pain behaviors and performing TMR 3 weeks after SNI reversed pain behaviors to baseline. By contrast, TMR performed at 12 weeks after SNI had no effect on pain behaviors. Neuroma excision resulted in significantly less reduction in hyperalgesia compared with TMR when performed 3 weeks after SNI but had no effect at 12 weeks after SNI. In this model, the pain phenotype induced by nerve transection is reduced by TMR when performed within 3 weeks after injury. However, TMR delayed 12 weeks after injury fails to reduce pain behaviors. This replicates clinical experience with limb amputation, supporting validity of this model for examining the mechanisms of TMR analgesia.

Variation on a technique for the intra-muscular insertion of nerve endings to minimise neuropathic and residual pain in lower limb amputees: a retrospective cohort study

IntroductionA major cause of morbidity in lower limb amputees is phantom limb pain (PLP) and residual limb pain (RLP). This study aimed to determine whether a variation of the surgical technique of inserting nerve endings into adjacent muscle bellies at the time of lower limb amputation can decrease the incidence and severity of PLP and RLP.MethodsData were retrospectively collected from January 2015 to January 2021, including eight patients that underwent nerve insertion (NI) and 36 that received standard treatment. Primary outcomes included the 11-point Numerical Rating Scale (NRS) for pain severity, and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behaviour, and interference. Secondary outcome included Neuro-QoL Lower Extremity Function assessing mobility. Cumulative scores were transformed to standardised t scores.ResultsAcross all primary and secondary outcomes, NI patients had lower PLP and RLP. Mean ‘worst pain’ score was 3.5 out of 10 for PLP in the NI cohort, compared to 4.89 in the control cohort (p = 0.298), and 2.6 out of 10 for RLP in the NI cohort, compared to 4.44 in the control cohort (p = 0.035). Mean ‘best pain’ and ‘current pain’ scores were also superior in the NI cohort for PLP (p = 0.003, p = 0.022), and RLP (p = 0.018, p = 0.134).Mean PROMIS t scores were lower for the NI cohort for RLP (40.1 vs 49.4 for pain intensity; p = 0.014, 44.4 vs 48.2 for pain interference; p = 0.085, 42.5 vs 49.9 for pain behaviour; p = 0.025). Mean PROMIS t scores were also lower for the NI cohort for PLP (42.5 vs 52.7 for pain intensity; p = 0.018); 45.0 vs 51.5 for pain interference; p = 0.015, 46.3 vs 51.1 for pain behaviour; p = 0.569). Mean Neuro-QoL t score was lower in NI cohort (45.4 vs 41.9; p = 0.03).ConclusionSurgical insertion of nerve endings into adjacent muscle bellies during lower limb amputation is a simple yet effective way of minimising PLP and RLP, improving patients’ subsequent quality of life. Additional comparisons with targeted muscle reinnervation should be performed to determine the optimal treatment option.

A Novel Nerve Isolation Technique for Targeted Muscle Reinnervation During Below-knee Amputation

Phantom limb pain (PLP) and neuroma-associated limb pain remain a significant challenge for many specialists who treat patients following major amputations. We present a novel technique for nerve isolation prior to targeted muscle reinnervation, which has shown promise in reducing and even eliminating PLP.

ProBDNF and Brain-Derived Neurotrophic Factor Prodomain Differently Modulate Acetylcholine Release in Regenerating and Mature Mouse Motor Synapses.

The effects of brain-derived neurotrophic factor (BDNF) processing by-products (proBDNF and BDNF prodomain) on the activity of mouse neuromuscular junctions (NMJs) were studied in synapses formed during the reinnervation of extensor digitorum longus muscle (m. EDL) and mature synapses of the diaphragm. The parameters of spontaneous miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) were analyzed in presence of each of the BDNF maturation products (both – 1 nM). In newly formed NMJs, proBDNF caused an increase in the resting membrane potential of muscle fibers and a decrease in the frequency of MEPPs, which was prevented by tertiapin-Q, a G-protein-coupled inwardly rectifying potassium channels (GIRK) blocker but not by p75 receptor signaling inhibitor TAT-Pep5. proBDNF had no effect on the parameters of EPPs. BDNF prodomain in newly formed synapses had effects different from those of proBDNF: it increased the amplitude of MEPPs, which was prevented by vesamicol, an inhibitor of vesicular acetylcholine (ACh) transporter; and reduced the quantal content of EPPs. In mature NMJs, proBDNF did not influence MEPPs parameters, but BDNF prodomain suppressed both spontaneous and evoked ACh release: decreased the frequency and amplitude of MEPPs, and the amplitude and quantal content of EPPs. This effect of the BDNF prodomain was prevented by blocking GIRK channels, by TAT-Pep5 or by Rho-associated protein kinase (ROCK) inhibitor Y-27632. At the same time, the BDNF prodomain did not show any inhibitory effects in diaphragm motor synapses of pannexin 1 knockout mice, which have impaired purinergic regulation of neuromuscular transmission. The data obtained suggest that there is a previously unknown mechanism for the acute suppression of spontaneous and evoked ACh release in mature motor synapses, which involves the activation of p75 receptors, ROCK and GIRK channels by BDNF prodomain and requires interaction with metabotropic purinoreceptors. In general, our results show that both the precursor of BDNF and the product of its maturation have predominantly inhibitory effects on spontaneous and evoked ACh release in newly formed or functionally mature neuromuscular junctions, which are mainly opposite to the effects of BDNF. The inhibitory influences of both proteins related to brain neurotrophin are mediated via GIRK channels of mouse NMJs.

Amputation–From the Routine to the Rotationplasty

Historically, extremity amputation was often the only surgical option for traumatic, infectious, or oncologic conditions. Despite evolution of surgical techniques and reconstructive options leading to successful limb sparing operations, amputation remains a viable and durable intervention for many conditions. The most common amputations are performed in the lower extremity and are due to complications of diabetes, peripheral vascular disease, or trauma. General principles and goals of amputations are to remove the pathology, allow for healing, maintain as much length as possible, and provide a stable base on which to weight bear. The barriers to successful outcomes include phantom pain, prosthetic cost, and short residual limbs resulting in difficulty with prosthetic wear.Musculoskeletal oncology is a specialty that affects all ages and anatomic locations. For malignancy of the pelvis and extremities that require an ablative procedure to attain oncologic control, there can be a variety of considerations and unusual situations resulting in difficulties in rehabilitation and functional restoration. A particularly challenging scenario is a malignancy presenting in the lower extremity of a growing child; in this case, a rotationplasty can provide superior function and durability.There have been advancements for amputees in the form of more sophisticated prostheses and rehabilitation protocols. In addition, there has been increased enthusiasm for surgical techniques reducing phantom pain or allowing for use of a myoelectric prosthesis (targeted muscle re‐innervation) and osseointegrative implants that allow for improvements in prosthetic use.

Gene delivery of chitosan-graft-polyethyleneimine vectors loaded on scaffolds for nerve regeneration

As an important transcription factor, c-Jun could upregulate growth factors expression in Schwann cells (SCs). Arginine-Glycine-Aspartate (RGD)-functionalized chitosan-graft-polyethyleneimine (RCP) gene vectors were prepared through the maleic anhydride & the carbodiimide methods, and electrostatically bound with c-Jun plasmids (pJUN), finally loaded on poly-L-lactic acid/silk fibroin parallel fiber films to fabricate nerve scaffold (RCP/pJUN-PSPF@PGA), which could locally deliver c-Jun plasmids into SCs via the mediation of RGD peptides, and upregulate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in SCs. After the scaffold was bridged in sciatic nerve defect, the delivery of c-Jun plasmids from RCP/pJUN-PSPF@PGA facilitated SCs to sustain the expressions of NGF, BDNF and vascular endothelial growth factor in the injury field, promoting myelination, axonal growth and microvascular generation and nerve regeneration, muscle reinnervation and functional recovery. These results suggested that RCP/pDNA-PSPF@PGA, as an effective gene delivery platform, could provide a local gene therapy to improve nerve regeneration.

Evaluating hip disarticulation outcomes in a 51-patient series

Hip disarticulations are proximal lower extremity amputations with high postoperative complication and mortality rates. The purpose of the study was to evaluate hip disarticulation outcomes at our institution. Targeted Muscle Reinnervation (TMR) is an effective surgical technique shown to reduce pain in amputees. A secondary goal of the study was to evaluate the impact of implementing TMR on this patient population. A retrospective review was performed for patients who underwent hip disarticulation with and without TMR between 2009 and 2020. Information on one-year mortality, thirty-day complication rates, operation times, surgical charges, and pain scores was collected. Fifty-one patients underwent hip disarticulation, eight of which had TMR performed at the time of their hip disarticulation. The one-year mortality rate was 37% with 30-day infection, readmission, reoperation, and rates of 37%, 39%, and 27% respectively. The thirty-day major complication rate was 47% overall but not statistically significantly different between groups. There were no differences between groups with regard to 30-day readmission, reoperation, and infection rates. Our results represent one of the largest series of hip disarticulation outcomes. Performing TMR at the time of hip disarticulation did not negatively affect outcomes and may be a beneficial adjunct to improve pain. Further research is warranted.

Targeted muscle reinnervation for a recurrent traumatic neuroma of the sural nerve: illustrative case

BACKGROUNDTraumatic neuromata often recur after resection. Recently, targeted muscle reinnervation (TMR) has been shown to be a promising alternative for the treatment of traumatic neuroma, also in nonamputees. This case shows that TMR can also be applied for this indication in recurrent traumatic neuroma.OBSERVATIONSA 55-year-old patient with a history of cerebral palsy presented with a painful swelling in his right knee, 40 years after multiple Achilles tendon surgeries for contractures. On imaging, the lesion was suspect for a traumatic neuroma of the posterior sural nerve. After two failed resections, TMR was performed by connecting the proximal end of the sural nerve to the motor branch of the lateral gastrocnemius muscle. During outpatient visits at 3, 6, and 12 months, the patient reported significantly less pain compared to before the TMR. He had no weakness of plantar flexion. Postoperative imaging, however, showed atrophy of the lateral gastrocnemius muscle.LESSONSThis case shows that TMR can be a successful strategy to treat recurrent traumatic neuroma after previous failed transection of single neuromata in nonamputee cases. In the authors’ patient, TMR did not result in motor deficit, but more research is needed to investigate this consequence of TMR for this indication.

Failed Targeted Muscle Reinnervation: Findings at Revision Surgery and Concepts for Success.

Background:Although it was initially described for improved myoelectric control, targeted muscle reinnervation (TMR) has quickly gained popularity as a technique for neuroma control. With this rapid increase in utilization has come broadening indications and variability in the described technique. As a result, it becomes difficult to interpret published outcomes. Furthermore, there is no literature discussing the management of failed cases which are undoubtedly occurring.Methods:This is a retrospective case series of two patients who underwent revision surgery for failed TMR. The authors also review the current literature on TMR and outline technical and conceptual pitfalls and pearls based on our local experience.Results:Excessive donor nerve redundancy, kinking, donor–recipient nerve size mismatch, superficial placement of the nerve coaptation, inappropriate target selection, and incomplete target muscle denervation were identified as technical pitfalls of TMR surgery. Techniques to avoid these pitfalls were described.Conclusions:Although TMR has been a major development in amputee care for both pain management and improved myoelectric control, it is important to acknowledge that it is not a foolproof surgery and does not provide a guaranteed result. Failed cases of TMR represent opportunities to learn about factors contributing to unfavorable outcomes and refine our techniques empirically.