Neuroma Prevention Research Articles

Buried filet of limb flaps for the reconstruction of forequarter and hindquarter amputations.

Forequarter and hindquarter amputations have traditionally been closed with local tissues, but the technique is plagued by a high rate of complication such as marginal necrosis, seroma, infection, and dehiscence. Filet of limb flaps have been used when local tissues are insufficient for closure, and despite their use in more extensive and complex wounds, outcomes seem to be better in these cases. Recognizing that filet of limb flaps not only serve to cover the wound, but also eliminate dead space, supplement at-risk and/or radiated tissue, pad underlying hard structures, and facilitate neuroma prevention with target muscle reinnervation, we have change our practice to utilize buried filet of limb flaps even when local tissues are technically "sufficient" to close the wound. The purpose of this article to organize and describe the ways in which buried filet-of-limb flaps can be used to achieve important and discrete surgical objectives in forequarter and hindquarter amputation, and to facilitate increased recognition of collaborative interdisciplinary opportunities for spare-part reconstruction. Retrospective data from the medical records of seven patients, collected between 2010 to 2023 at our single tertiary referral center, were reviewed. This included all patients for whom a buried (or partially buried) filet of limb flap was attempted for forequarter or hindquarter amputation reconstruction. Five males and two females ranging 55 to 75 years of age, met the inclusion criteria. Three cases of forequarter amputation and four cases of hindquarter amputation were included. Six flaps were successfully transferred without major flap-related complications. The mean follow-up period was eight and a half months. Even when local tissues are technically "sufficient" to close forequarter and hindquarter amputation wounds, we have found buried filet of limb flaps to be useful in several ways. These include occupying dead space, providing double-layer coverage, padding hard structures, preventing neuromas, and reconstructing sacro- and spino-pelvic continuity. Our approach emphasizes interdisciplinary collaboration and highlights the potential advantages of buried filet of limb flaps in optimizing patient outcomes for complex limb amputations.

A National Analysis of Targeted Muscle Reinnervation Following Major Upper Extremity Amputation.

Post-amputation pain is a debilitating sequela of upper extremity (UE) amputation. Targeted muscle reinnervation (TMR) is a relatively novel treatment that can help prevent pain and improve quality of life. The purpose of this study is to evaluate national trends in the application of immediate TMR following UE amputations. . An analysis of the Nationwide Inpatient Sample database was conducted from 2016-2019. ICD-10 codes were used to identify encounters involving UE amputation with and without TMR. NIS weights were used to estimate national estimates of incidence. Patient-specific and hospital-specific factors were analyzed to assess associations with use of TMR. A total of 8,945 weighted encounters underwent UE amputation, and of those, only 310 (3.5%) received TMR. The majority of TMR occurred in urban hospitals (>95%). Younger patients (47 vs. 54, p=0.008) and patients located in New England were significantly more likely to receive TMR. There was no difference in total cost of hospitalization amongst patients who received TMR ($55,241 vs $59,027.8, p=0.683) but significantly shorter lengths of hospital stay when receiving TMR versus other management (10.6 vs. 14.8, p=0.012). TMR has purported benefits of pain reduction, neuroma prevention, and increased prosthetic control. Access to this beneficial procedure following UE amputation varies by demographics and geographic region. Given that TMR has not been shown to increase cost while simultaneously decreasing patient length of stay, increased efforts to incorporate this procedure into training and practice will help to ensure equitable care for amputation patients. .

Nerve Capping Techniques for Neuroma Management: A Comprehensive Literature Review.

Nerve capping is a method of neuroma treatment or prevention that consists of the transplantation of a proximal nerve stump into an autograft or other material cap, after surgical removal of the neuroma or transection of the nerve. The aim was to reduce neuroma formation and symptoms by preventing neuronal adhesions and scar tissue. In this narrative literature review, we summarize the studies that have investigated the effectiveness of nerve capping for neuroma management to provide clarity and update the clinician's knowledge on the topic. A systematic electronic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was performed in the PubMed database combining "neuroma," "nerve," "capping," "conduit," "treatment," "management," "wrap," "tube," and "surgery" as search terms. English-language clinical studies on humans and animals that described nerve capping as a treatment/prevention technique for neuromas were then selected based on a full-text article review. The data from the included studies were compiled based on the technique and material used for nerve capping, and technique and outcomes were reviewed. We found 10 applicable human studies from our literature search. Several capping materials were described: epineurium, nerve, muscle, collagen nerve conduit, Neurocap (synthetic copolymer of lactide and caprolactone, which is biocompatible and resorbable), silicone rubber, and collagen. Overall, 146 patients were treated in the clinical studies. After surgery, many patients were completely pain-free or had considerable improvement in pain scores, whereas some patients did not have improvement or were not satisfied after the procedure. Nerve capping was used in 18 preclinical animal studies, using a variety of capping materials including autologous tissues, silicone, and synthetic nanofibers. Preclinical studies demonstrated successful reduction in rates of neuroma formation. Nerve capping has undergone major advancements since its beginnings and is now a useful option for the treatment or prevention of neuromas. As knowledge of peripheral nerve injuries and neuroma prevention grows, the criterion standard neuroprotective material for enhancement of nerve regeneration can be identified and applied to produce reliable surgical outcomes.

Improving outcomes in traumatic peripheral nerve injuries to the upper extremity.

Peripheral nerve lesions of the upper extremity are common and are associated with devastating limitations for the patient. Rapid and accurate diagnosis of the lesion by electroneurography, neurosonography, or even MR neurography is important for treatment planning. There are different therapeutic approaches, which may show individual differences depending on the injured nerve. If a primary nerve repair is not possible, several strategies exist to bridge the gap. These may include autologous nerve grafts, bioartificial nerve conduits, or acellular nerve allografts. Tendon and nerve transfers are also of major importance in the treatment of nerve lesions in particular with long regeneration distances. As a secondary reconstruction, in addition to tendon transfers, there is also the option for free functional muscle transfer. In amputations, the prevention of neuroma is of great importance, for which different strategies exist, such as target muscle reinnervation, regenerative peripheral nerve interface, or neurotized flaps. In this article, we give an overview of the latest methods for the therapy of peripheral nerve lesions.

The Double-Opposing Adipofascial Interposition Flap: A Novel Technique to Prevent Scar Tethering and Symptomatic Neuroma of the Superficial Radial Nerve After Trauma.

The superficial radial nerve (SRN) is vulnerable to injury following trauma with a high incidence of resultant nerve tether and neuroma formation. The SRN has an anatomical predisposition to neuroma formation, with research indicating that its propensity to neuroma development is out of proportion with its likelihood for injury. In addition, SRN neuromas havebeen described as one of the more painful and difficult neuromas to manage. Despite this, the published literature to date is chiefly focused on neuroma and scar tether treatment options rather than more impactful work on neuroma prevention, which can be safely delivered at the time of primary surgery. Treatment of established neuroma or nerve tether is notoriously difficult, and existing techniques have inconsistent outcomes, with patients often requiring multiple trips to the theatre. The authors present a novel technique for neuroma and scar tether prevention using an adipofascial flap accompanied by patient examples of our experience using this approach as an adjunct during the primary SRN repair, creating a gliding, interposing layer to prevent subsequent nerve traction pain and symptomatic neuroma. We identified five patients presenting with dorsal wrist injuries involving the SRN and one or more tendons. Patients' follow-up duration was a mean of 3.5 months (one to eight months). All follow-up patients showed no symptoms of a neuroma or nerve tether pain. All patients were discharged without re-referral or further surgery. Our patient sample demonstrates promising results using an adipofascial interposition flap as a prophylactic measure in traumatic injuries to reduce nerve tether pain and symptomatic neuroma formation in the SRN.

Experience with ultrasound neurography for postoperative evaluation of targeted muscle reinnervation.

Targeted muscle reinnervation (TMR) was originally developed as a means for increasing intuitive prosthesis control, though later found to play a role in phantom limb pain and neuroma prevention. There is a paucity of literature describing the clinical course of patients with poor TMR surgical outcomes and the value of imaging in the postoperative recovery period. This report will illustrate the potential utility of ultrasound neurography to accurately differentiate TMR surgical outcomes in two patients that received upper extremity amputation and subsequent reconstruction with TMR. Ultrasound evaluation of TMR sites in patient 1 confirmed successful reinnervation, evident by nerve fascicle continuity and eventual integration of the transferred nerve into the target muscle. Conversely, the ultrasound of patient 2 showed discontinuity of the nerve fascicles, neuroma formation, and muscle atrophy in all three sites of nerve transfer, suggesting an unsuccessful procedure and poor functional recovery. Ultrasound neurography is uniquely able to capture the longitudinal trajectory of rerouted nerves to confirm continuity and eventual reinnervation into muscle. Therefore, the application of ultrasound in a postoperative setting can correctly identify instances of failed TMR before this information would become available through clinical evaluation. Early identification of poor TMR outcomes may benefit future patients by fostering the discovery of failure mechanisms and aiding in further surgical planning to improve functional outcomes.

Primary Regenerative Peripheral Nerve Interfaces Using Devascularized Vastus Lateralis Muscle in Sensate Anterolateral Thigh Flap Donor Sites.

Sensate flaps are increasingly used in diverse areas of plastic surgery. Concurrently, modern techniques in neuroma prevention have emerged, such as regenerative peripheral nerve interface (RPNI). Despite increasing use of sensate flaps, the combined use of donor-site neuroma prevention techniques has yet to be described. We report on the use of primary donor-site RPNI at the time of sensate anterolateral thigh (ALT) reconstructions. In ALT flaps, the vastus lateralis muscle can be segmentally devascularized from perforator dissection. These segments of devascularized vastus lateralis muscle can easily be used and repurposed as the free muscle grafts needed for RPNI, providing a physiologic target for the regenerating neurons. Donor-site neuroma has not been shown to be a significant issue at standard ALT flap donor sites. Sensate ALT flaps involve harvest of the lateral femoral cutaneous nerve and/or additional femoral sensory branches at a more proximal location close to the level of the anterior superior iliac spine, where injury to the lateral femoral cutaneous nerve may be associated with pain. In this series, eight patients underwent senate ALT flaps with the use of primary RPNI at the sensate ALT donor site. At a mean follow-up of 16.3 months (range 5-25 months), there was minimal to no nerve pain and no clinical evidence of donor-site neuroma. As sensate flap reconstructions are increasingly performed in plastic surgery and data on neuroma prevention techniques continue to grow, we propose consideration of their combined use.

Nerve Defect Treatment with a Capping Hydroxyethyl Cellulose/Soy Protein Isolate Sponge Conduit for Painful Neuroma Prevention.

Painful neuroma, as one of the complications of nerve injury from disease or trauma, results in instinctive neuropathic pain that adversely affects a patient's quality of life. To intercept neuroma development, capping strategies have been performed as effective therapies. Nonetheless, the most appropriate biocompatible material to shield the nerves is an urgent clinical requirement. Herein, a compatible hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) sponge capping conduit (HSSC) is used to prevent neuroma in vivo. Following capping on the sciatic nerve stump in vivo, the behavior of the rats and the structure of tissues are compared through histological assessment and autotomy scoring. The HSSCs gained a dismal autotomy score and enhanced the amelioration, where inflammatory invasions and overdeposition of collagen are defeated. The expression of myelin growth linked genes (Krox20, MPZ, and MAG) in the HSSC group at the eighth week was almost 2 times higher than that of the no capping group. The HSSC conduit served as a physical barrier to repress the infiltration of inflammation as well as provided an optimum microenvironment for facilitating nerve rejuvenation and intercepting neuroma development during nerve amelioration.

Regenerative Peripheral Nerve Interface Surgery: Anatomic and Technical Guide.

Regenerative peripheral nerve interface (RPNI) surgery has been demonstrated to be an effective tool as an interface for neuroprosthetics. Additionally, it has been shown to be a reproducible and reliable strategy for the active treatment and for prevention of neuromas. The purpose of this article is to provide a comprehensive review of RPNI surgery to demonstrate its simplicity and empower reconstructive surgeons to add this to their armamentarium. This article discusses the basic science of neuroma formation and prevention, as well as the theory of RPNI. An anatomic review and discussion of surgical technique for each level of amputation and considerations for other etiologies of traumatic neuromas are included. Lastly, the authors discuss the future of RPNI surgery and compare this with other active techniques for the treatment of neuromas.

52. Varying Muscle Graft to Nerve Fiber Size and its Impact on Regenerative Peripheral Nerve Interface (RPNI) Reinnervation

PURPOSE: Currently there are more than 1.6 million people who suffer from limb loss. Regenerative Peripheral Nerve Interfaces (RPNI) currently exist as a method of capturing peripheral nerve signals for prosthetic control and preventing neuroma formation. While it is typically recommended that RPNIs are constructed to be 3 x 1 x 1.5 cm for human patients and approximately 150 mg in rat models, there is currently no recommendations or data to guide selection of muscle graft size for different nerve sizes. This consideration is especially important for RPNI construction as these factors may influence maximal optimal reinnervation for motor signal capture and neuroma prevention. The purpose of this study was to assess the ideal ratio of nerve size to muscle graft size for maximal RPNI compound muscle action potential (CMAP) signaling. METHODS: A total of 46 rats were assigned to 6 experimental groups that varied the size of nerve and muscle graft for RPNI creation. Extensor digitorum longus (EDL) was harvested, and different combinations of its four muscle heads were removed to create different size muscle grafts: 20% EDL, 60% EDL, and 100%EDL. To adjust nerve size, the tibial nerve was either left untouched or divided longitudinally along the nerve for approximately 15 cm. Depending on the experimental group, either 33% or 100% of the tibial nerve was implanted into the final muscle graft. All rats underwent a 3-month maturation period before undergoing electrophysiologic testing for obtaining CMAPs. An ANOVA test with post hoc analysis was performed to test for significant differences among the groups. RESULTS: For 33% nerve groups, maximum average CMAPs occurred at 2.2 mV with the 60% EDL RPNI. However, this average was not statistically different from that of the 20% (0.47 mV) or 100% (1.85 mV) EDL RPNI. With the 100% nerve group, maximum CMAP of the 100% EDL RPNI (4.5 mV) was significantly greater than that of the 20% (1.7 mV) or 60% (2.3 mV) EDL RPNIs. Furthermore, the maximum average CMAPs of the 100% nerve was significantly higher from that of the 33% nerve. CONCLUSIONS: This study’s findings suggest RPNI regeneration by large nerves requires the full EDL donor muscle for maximal reinnervation in the rat model, and that full reinnervation leads to significantly larger motor signals compared to smaller nerves. Thus, muscle graft size optimization to nerve size may be necessary in the clinical setting.

Symptomatic Neuroma Development following En Bloc Resection of Skeletal and Soft-Tissue Tumors: A Retrospective Analysis of 331 Cases.

Although symptomatic neuroma formation has been described in other patient populations, these data have not been studied in patients undergoing resection of musculoskeletal tumors. This study aimed to characterize the incidence and risk factors of symptomatic neuroma formation following en bloc resection in this population. The authors retrospectively reviewed adults undergoing en bloc resections for musculoskeletal tumors at a high-volume sarcoma center from 2014 to 2019. The authors included en bloc resections for an oncologic indication and excluded non-en bloc resections, primary amputations, and patients with insufficient follow-up. Data are provided as descriptive statistics, and multivariable regression modeling was performed. The authors included 231 patients undergoing 331 en bloc resections (female, 46%; mean age, 52 years). Nerve transection was documented in 87 resections (26%). There were 81 symptomatic neuromas (25%) meeting criteria of Tinel sign or pain on examination and neuropathy in the distribution of suspected nerve injury. Factors associated with symptomatic neuroma formation included age 18 to 39 [adjusted OR (aOR), 3.6; 95% CI, 1.5 to 8.4; P < 0.01] and 40 to 64 (aOR, 2.2; 95% CI, 1.1 to 4.6; P = 0.04), multiple resections (aOR, 3.2; 95% CI, 1.7 to 5.9; P < 0.001), preoperative neuromodulator requirement (aOR, 2.7; 95% CI, 1.2 to 6.0; P = 0.01), and resection of fascia or muscle (aOR, 0.5; 95% CI, 0.3 to 1.0; P = 0.045). The authors' results highlight the importance of adequate preoperative optimization of pain control and intraoperative prophylaxis for neuroma prevention following en bloc resection of tumors, particularly for younger patients with a recurrent tumor burden. Risk, III.

44. Symptomatic Neuroma Formation following Skeletal and Soft Tissue Tumor Resection

PURPOSE: While symptomatic neuroma formation has been described in other patient populations, these data have not been studied in patients undergoing resection of musculoskeletal tumors. This study aims to characterize the incidence and risk factors of symptomatic neuroma formation following en bloc resection in this population. METHODS: We retrospectively reviewed adults undergoing en bloc resections for musculoskeletal tumors at a high-volume sarcoma center from 2014-2019. We included en bloc resections for an oncologic indication and excluded non-en bloc resections, primary amputations, and patients with insufficient follow-up. Data are provided as descriptive statistics and multivariable regression modeling was performed. RESULTS: We included 231 patients undergoing 331 en bloc resections (46% female; mean age 52 years). Nerve transection was documented in 87 resections (26%). There were 81 symptomatic neuromas (25%) meeting criteria of Tinel sign or pain on exam and neuropathy in the distribution of suspected nerve injury. Factors associated with symptomatic neuroma formation included age 18-39 (aOR, 3.6; 95% CI, 1.5-8.4; p < 0.01) and 40-64 (aOR, 2.2; 95% CI, 1.1-4.6; p = 0.04), multiple resections (aOR, 3.2; 95% CI, 1.7-5.9; p < 0.001), preoperative neuromodulator requirement (aOR, 2.7; 95% CI 1.2-6.0; p = 0.01) and resection of fascia or muscle (aOR, 0.5; 95% CI, 0.3-1.0; p = 0.045). CONCLUSION: Our results highlight the importance of adequate preoperative optimization of pain control and intraoperative prophylaxis for neuroma prevention following en bloc resection of tumors, particularly for younger patients with a recurrent tumor burden.

New techniques and methods for prevention and treatment of symptomatic traumatic neuroma: A systematic review.

Generally, axons located at the central end of the nerve system will sprout after injury. Once these sprouts cannot reach the distal end of the severed nerve, they will form a traumatic neuroma. Traumatic neuromas bring a series of complex symptoms to patients, such as neuropathic pain, skin abnormalities, skeletal abnormalities, hearing loss, and visceral damage. To date, the most promising and practical clinical treatments are drug induction and surgery, but both have their limitations. Therefore, it will be the mainstream trend to explore new methods to prevent and treat traumatic neuroma by regulating and remodeling the microenvironment of nerve injury. This work first summarized the pathogenesis of traumatic neuroma. Additionally, the standard methods of prevention and treatment on traumatic neuroma were analyzed. We focused on three essential parts of advanced functional biomaterial therapy, stem cell therapy, and human-computer interface therapy to provide the availability and value of preventing and treating a traumatic neuroma. Finally, the revolutionary development of the prevention and treatment on traumatic neuroma has been prospected. How to transform the existing advanced functional materials, stem cells, and artificial intelligence robots into clinical practical technical means as soon as possible for high-quality nerve repair and prevention of neuroma was further discussed.

Regenerative peripheral nerve interface prevents neuroma formation after peripheral nerve transection.

Neuroma formation after peripheral nerve transection often leads to severe neuropathic pain. Regenerative peripheral nerve interface has been shown to reduce painful neuroma in the clinic. However, no reports have investigated the underlying mechanisms, and no comparative animal studies on regenerative peripheral nerve interface and other means of neuroma prevention have been conducted to date. In this study, we established a rat model of left sciatic nerve transfection, and subsequently interfered with the model using the regenerative peripheral nerve interface or proximal nerve stump implantation inside a fully innervated muscle. Results showed that, compared with rats subjected to nerve stump implantation inside the muscle, rats subjected to regenerative peripheral nerve interface intervention showed greater inhibition of the proliferation of collagenous fibers and irregular regenerated axons, lower expressions of the fibrosis marker α-smooth muscle actin and the inflammatory marker sigma-1 receptor in the proximal nerve stump, lower autophagy behaviors, lower expressions of c-fos and substance P, higher expression of glial cell line-derived neurotrophic factor in the ipsilateral dorsal root ganglia. These findings suggested that regenerative peripheral nerve interface inhibits peripheral nerve injury-induced neuroma formation and neuropathic pain possibly via the upregulation of the expression of glial cell line-derived neurotrophic factor in the dorsal root ganglia and reducing neuroinflammation in the nerve stump.

Development of an acellular nerve cap xenograft for neuroma prevention.

Neuroma formation following limb amputation is a prevalent and debilitating condition that can deeply affect quality of life and productivity. Several approaches exist to prevent or treat neuromas; however, no approach is either consistently reliable or surgically facile, with high rates of neuroma occurrence and/or recurrence. The present study describes the development and testing of a xenogeneic nerve cap graft made from decellularized porcine nerve. The grafts were tested in vitro for cellular removal, cytotoxicity, mechanical properties, and morphological characteristics. The grafts were then tested in rat sciatic nerve gap reconstruction and nerve amputation models for 8 weeks. Gross morphology, electrophysiology, and histopathology assessments were performed to determine the ability of the grafts to limit pathologic nerve regrowth. In vitro testing showed well decellularized and demyelinated nerve cap graft structures without any cytotoxicity from residual reagents. The grafts had a proximal socket for the proximal nerve stump and longitudinally oriented internal pores. Mechanical and surgical handling properties suggested suitability for implantation as a nerve graft. Following 8 weeks in vivo, the grafts were well integrated with the proximal and distal nerve segments without evidence of fibrotic adhesions to the surrounding tissues or bulbous outgrowth of the nerve. Electrophysiology revealed absence of nerve conduction within the remodeled nerve cap grafts and significant downstream muscle atrophy. Histologic evaluation showed well organized but limited axonal regrowth within the grafts without fibrous overgrowth or neuromatous hypercellularity. These results provide proof of concept for a novel xenograft-based approach to neuroma prevention.

Regenerative Peripheral Nerve Interfaces Effectively Prevent Neuroma Formation After Sciatic Nerve Transection in Rats.

ObjectiveThe disordered growth of nerve stumps after amputation leading to the formation of neuromas is an important cause of postoperative pain in amputees. This severely affects the patients' quality of life. Regenerative peripheral nerve interfaces (RPNIs) are an emerging method for neuroma prevention, but its postoperative nerve growth and pathological changes are yet to be studied.MethodsThe rat sciatic nerve transection model was used to study the effectiveness of RPNI in this experiment. The RPNI (experimental) group (n = 11) underwent RPNI implantation after sciatic nerve transection, while the control group (n = 11) only underwent sciatic nerve transection. Autotomy behavior, ultrasonography, and histopathology were observed for 2 months postoperatively.ResultsCompared to the control group, the incidence and size of the neuromas formed and the incidence and extent of autotomy were significantly reduced in the RPNI group. The axon density in the stump and degree of stump fibrosis were also significantly reduced in the RPNI group.ConclusionRPNI effectively prevented the formation of neuromas.

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.

Surgical Approaches for Prevention of Neuroma at Time of Peripheral Nerve Injury.

Painful neuroma is a frequent sequela of peripheral nerve injury which can result in pain and decreased quality of life for the patient, often necessitating surgical intervention. End neuromas are benign neural tumors that commonly form after nerve transection, when axons from the proximal nerve stump regenerate in a disorganized manner in an attempt to recreate nerve continuity. Inflammation and collagen remodeling leads to a bulbous end neuroma which can become symptomatic and result in decreased quality of life. This review covers surgical prophylaxis of end neuroma formation at time of injury, rather than treatment of existing neuroma and prevention of recurrence. The current accepted methods to prevent end neuroma formation at time of injury include different mechanisms to inhibit the regenerative response or provide a conduit for organized regrowth, with mixed results. Approaches include proximal nerve stump capping, nerve implantation into bone, muscle and vein, various pharmacologic methods to inhibit axonal growth, and mechanisms to guide axonal growth after injury. This article reviews historical treatments that aimed to prevent end neuroma formation as well as current and experimental treatments, and seeks to provide a concise, comprehensive resource for current and future therapies aimed at preventing neuroma formation.

Local Environment Induces Differential Gene Expression in Regenerating Nerves

IntroductionApproximately 80% of amputations are complicated by neuromas. Methods for neuroma management include nerve translocation into bone and implantation into skeletal muscle grafts, which have also facilitated the development of regenerative neural interfaces to enable fixation of prosthetics with motor and sensory feedback. However, molecular-level differences between nerves in these environments have not been investigated. This study aimed to elucidate the physiology of regenerating nerves in different settings by assessing gene expression. Materials and methodsNew Zealand white rabbits underwent transfemoral amputation with sciatic nerve transposition into the femur or tacked to skeletal muscle. At 5 wk, ribonucleic acid (RNA) sequencing of samples of distal nerve terminating in bone or muscle and nerve of the contralateral limb (control) identified differentially expressed genes (DEGs) and biochemical pathways (α = 0.05). ResultsThree samples of nerve housed in bone, four of nerve tacked to muscle, and seven naïve controls were analyzed. Relative to controls, nerve housed in bone had little within-group variation and 13,028 DEGs, and nerve tacked to muscle had dramatic within-group variation and 12,811 DEGs. These samples upregulated the following pathways: lysosome, phagosome, antigen processing/presentation, and cell adhesion molecule. Relative to nerve housed in bone, nerve tacked to muscle had 12,526 DEGs, demonstrating upregulation of pathways of B-cell receptor signaling, focal adhesion, natural killer–cell mediated cytotoxicity, leukocyte transendothelial migration, and extracellular matrix–receptor interactions. ConclusionsNerve housed in bone has a more predictable molecular profile than does nerve tacked to muscle. Thus, the intramedullary canal may provide a more reliable setting for neuroma prevention and neural interfacing.

Digital Nerve Management and Neuroma Prevention in Hand Amputations.

Hand and digit amputations represent a relatively common injury affecting an active patient population. Neuroma formation following amputation at the level of the digital nerve can cause significant disability and lead to revision surgery. One method for managing digital nerves in primary and revision partial hand amputations is to perform interdigital end-to-end nerve coaptations to prevent neuroma formation. All patients with an amputation at the level of the common or proper digital nerves that had appropriate follow-up at our institution from 2010 to 2020 were included. Common or proper digital nerves were managed with either traction neurectomy or digital end-to-end neurorrhaphy. The primary outcome was the development of a neuroma. Secondary outcomes included revision surgery, complications, and visual analog pain scores. A total of 289 nerves in 54 patients underwent hand or digital amputation in the study period. Thirteen hands with 78 nerves (27%) underwent direct end-to-end coaptation with a postoperative neuroma incidence of 12.8% compared with 22.7% in the 211 nerves that did not have a coaptation performed. Significantly fewer patients reported persistent pain if an end-to-end coaptation was performed (0% vs. 11.8%, P < .01). The prevalence of depression and workers compensation status was significantly higher in in patients with symptomatic neuromas than in patients without symptomatic neuromas (P < .01). Digital nerve end-to-end neurorrhaphy is a method for neuroma prevention in partial hand amputations that results in decreased residual hand pain without increase complications. Depression and worker's compensations status were significantly associated with symptomatic neuroma formation.