Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.

Raman difference spectroscopy and U-Net convolutional neural network for molecular analysis of cutaneous neurofibroma.

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins-complete tumor removal while attempting to preserve viable tissue-remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

Utility of MR Neurography for the Evaluation of Peripheral Trigeminal Neuropathies in the Postoperative Period.

Peripheral trigeminal neuropathies are assessed by MR neurography for presurgical mapping. In this clinical report, we aimed to understand the utility of MR neurography following nerve-repair procedures. We hypothesized that postoperative MR neurography assists in determining nerve integrity, and worsening MR neurography findings will corroborate poor patient outcomes. Ten patients with peripheral trigeminal neuropathy were retrospectively identified after nerve-repair procedures, with postsurgical MR neurography performed from July 2015 to September 2023. Postsurgical MR neurography findings were graded as per postintervention category and subcategories of the Neuropathy Score Reporting and Data System (NS-RADS). Descriptive statistics of demographics, inciting injury, injury severity, NS-RADS scoring, and clinical outcomes were obtained. There were 6 women and 4 men (age range, 25-73 years). Most injuries resulted from third molar removals (8/10), with an average time from the inciting event to nerve-repair surgery of 6.1 (SD, 4.6) months. In Neuropathy Score Reporting and Data System-Injury (NS-RADS I), NS-RADS I-4 injuries (neuroma in continuity) were found in 8/10 patients, and NS-RADS I-5 injuries were found in the remaining patients, all confirmed at surgery. Surgeries performed included microdissection with neurolysis, neuroma excision, and nerve allograft with Axoguard protection. Three patients with expected postsurgical MR neurography findings experienced either partial improvement or complete symptom resolution, while among 7 patient with persistent or recurrent neuropathy on postsurgical MR neurography, one demonstrated partial improvement of sensation, pain, and taste and one experienced only pain improvement; the remaining 5 patients demonstrated no improvement. Postsurgical MR neurography consistently coincided with clinical outcomes related to pain, sensation, and lip biting and speech challenges. Lip biting and speech challenges were most amenable to recovery, even with evidence of persistent nerve pathology on postsurgical MR neurography.

Infrapatellar Branch of the Saphenous Nerve: Therapeutic Approaches to Chronic Knee Pain.

PURPOSE OF REVIEW: The infrapatellar branch of the saphenous nerve (IPS) is an under-investigated nerve that can be a source of chronic knee pain. This literature review aims to deliver an up-to-date review of chronic pain transmitted via the IPS along with therapeutic approaches available for pain refractory to conservative measures. RECENT FINDINGS: Knee pain transmitted via the IPS can arise from several etiologies. Damage to the IPS is often iatrogenic and develops following total knee arthroplasty, anterior cruciate ligament reconstruction, and other knee surgical procedures. Other causes of IPS-derived pain include entrapment of the nerve, neuromas, Schwannomas, and pain from knee osteoarthritis transmitted through the IPS.This article investigated therapeutic approaches to pain derived from the IPS. Common approaches included radiofrequency ablation, neuroma excisions, Schwannoma excision, nerve blocks, surgical exploration, surgical release of an entrapped nerve, cryoablation, and peripheral nerve stimulation. Pain scores, duration of pain relief, adverse events, and secondary outcomes were all included in this review. A subset of the patient population experiences chronic pain deriving from the IPS that is refractory to conservative treatment measures. This review aims to evaluate the etiologies and therapeutic approaches for chronic pain arising from the IPS refractory to conservative treatments.

Neuropathic pain of the superficial branch of the radial nerve - Factors influencing surgical outcome and patient satisfaction.

BACKGROUND: Due to its partially superficial course, the superficial branch of the radial nerve is vulnerable to injury by trauma or surgery, potentially leading to painful neuroma. Surgical treatment is difficult. Among other factors, smoking and duration of pain before revision surgery have been suggested as risk factors for persistent pain after surgical revision, without concrete evidence. The aim of this study was therefore to identify factors influencing the outcome of revision surgery in SBRN neuropathic pain in our department. METHODS: All 51 patients receiving revision surgery of the superficial branch of the radial nerve for neuropathic pain from 2010 to 2020 were contacted; 19 agreed to return for assessment. A medical chart review was performed to collect patient-, pain- and treatment-specific factors. Outcomes were recorded. In an outpatient consultation, clinical follow-up was performed and patients filled out the DASH, MHQ and painDETECT questionnaires. RESULTS: After revision surgery, all patients experienced persistent pain. On multivariate logistic regression evaluating the risk of persistent pain, only smoking emerged as an independent risk factor. Age, gender, dominant side, location, time between trigger and surgery or diagnosis did not emerge as risk factors. No predictor for successful return to work could be identified. CONCLUSIONS: Treatment of painful neuroma of the superficial branch of the radial nerve is a challenge. Patients with neuropathic pain should be coached toward smoking cessation before neuroma surgery. Surgery can show benefit even after long symptom duration. No correlations between study clinical variables or test results and return to work could be identified, suggesting that other factors play a role in return to work.

Multiple palisaded encapsulated neuromas presenting as cobblestoned plaques over palms and oral cavity.

Palisaded encapsulated neuroma (PEN) is a benign circumscribed nerve sheath tumor usually seen as a solitary painless papule on the face in middle-aged adults. We report a 22-year-old male with multiple adolescent-onset PENs distributed extensively, including the oral cavity and palms, contrary to the typical presentations. The lesions formed cobblestoned plaques and were confirmed through a skin biopsy, showing characteristic nodules of wavy spindle cells forming interlacing fascicles with interspersed clefts, and positive staining for specific markers, including markers for axons and perineurium. Notably, this case deviates from the usual presentation, shedding light on atypical manifestations of PEN in a young individual without any features suggestive of a neurocutaneous syndrome or multiple endocrine neoplasia syndrome.

Anatomy of the Superficial Radial Nerve and Its Target Nerves for Targeted Muscle Reinnervation: An Anatomical Cadaver Study.

BACKGROUND: Targeted muscle reinnervation (TMR) is a surgical procedure for treating symptomatic neuroma, in which the neuroma is removed and the proximal nerve stump is coapted to a donor motor branch innervating a nearby muscle. This study aimed to identify optimal motor targets for TMR of the superficial radial nerve (SRN). METHODS: Seven cadaveric upper limbs were dissected to describe the course of the SRN in the forearm and motor nerve supply-number, length, diameter, and entry points in muscle of motor branches-for potential recipient muscles. RESULTS: The radial nerve provided three (three of six) motor branches, two (two of six) motor branches, or one (one of six) motor branch to the brachioradialis muscle, entering the muscle 21.7 ± 17.9 to 10.8 ± 15 mm proximal to the lateral epicondyle. One (one of seven), two (three of seven), three (two of seven), or four (one of seven) motor branches innervated the extensor carpi radialis longus muscle, with entry points 13.9 ± 16.2 to 26.3 ± 14.9 mm distal from the lateral epicondyle. In all specimens, the posterior interosseous nerve gave off one motor branch to the extensor carpi radialis brevis, which divided into two or three secondary branches. The distal anterior interosseus nerve was assessed as a potential recipient for TMR coaptation and had a freely transferable length of 56.4 ± 12.7 mm. CONCLUSIONS: When considering TMR for neuromas of the SRN in the distal third of the forearm and hand, the distal anterior interosseus nerve is a suitable donor target. For neuromas of the SRN in the proximal two-thirds of the forearm, the motor branches to the extensor carpi radialis longus, extensor carpi radialis brevis, and brachioradialis are potential donor targets.

Targeted Muscle Reinnervation at the Time of Amputation Decreases Recurrent Symptomatic Neuroma Formation.

BACKGROUND: Targeted muscle reinnervation (TMR) is an effective technique for the prevention and management of phantom limb pain (PLP) and residual limb pain (RLP) among amputees. The purpose of this study was to evaluate symptomatic neuroma recurrence and neuropathic pain outcomes between cohorts undergoing TMR at the time of amputation (ie, acute) versus TMR following symptomatic neuroma formation (ie, delayed). METHODS: A cross-sectional, retrospective chart review was conducted using patients undergoing TMR between 2015 and 2020. Symptomatic neuroma recurrence and surgical complications were collected. A subanalysis was conducted for patients who completed Patient-Reported Outcome Measurement Information System (PROMIS) pain intensity, interference, and behavior scales and an 11-point numeric rating scale (NRS) form. RESULTS: A total of 105 limbs from 103 patients were identified, with 73 acute TMR limbs and 32 delayed TMR limbs. Nineteen percent of the delayed TMR group had symptomatic neuromas recur in the distribution of original TMR compared with 1% of the acute TMR group ( P < 0.05). Pain surveys were completed at final follow-up by 85% of patients in the acute TMR group and 69% of patients in the delayed TMR group. Of this subanalysis, acute TMR patients reported significantly lower PLP PROMIS pain interference ( P < 0.05), RLP PROMIS pain intensity ( P < 0.05), and RLP PROMIS pain interference ( P < 0.05) scores in comparison to the delayed group. CONCLUSIONS: Patients who underwent acute TMR reported improved pain scores and a decreased rate of neuroma formation compared with TMR performed in a delayed fashion. These results highlight the promising role of TMR in the prevention of neuropathic pain and neuroma formation at the time of amputation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

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

BACKGROUND/AIM OF THE STUDY: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Biology and pathophysiology of symptomatic neuromas.

ABSTRACT: Neuromas are a substantial cause of morbidity and reduction in quality of life. This is not only caused by a disruption in motor and sensory function from the underlying nerve injury but also by the debilitating effects of neuropathic pain resulting from symptomatic neuromas. A wide range of surgical and therapeutic modalities have been introduced to mitigate this pain. Nevertheless, no single treatment option has been successful in completely resolving the associated constellation of symptoms. While certain novel surgical techniques have shown promising results in reducing neuroma-derived and phantom limb pain, their effectiveness and the exact mechanism behind their pain-relieving capacities have not yet been defined. Furthermore, surgery has inherent risks, may not be suitable for many patients, and may yet still fail to relieve pain. Therefore, there remains a great clinical need for additional therapeutic modalities to further improve treatment for patients with devastating injuries that lead to symptomatic neuromas. However, the molecular mechanisms and genetic contributions behind the regulatory programs that drive neuroma formation-as well as the resulting neuropathic pain-remain incompletely understood. Here, we review the histopathological features of symptomatic neuromas, our current understanding of the mechanisms that favor neuroma formation, and the putative contributory signals and regulatory programs that facilitate somatic pain, including neurotrophic factors, neuroinflammatory peptides, cytokines, along with transient receptor potential, and ionotropic channels that suggest possible approaches and innovations to identify novel clinical therapeutics.

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.

Phantom Limb Pain and Painful Neuroma After Dysvascular Lower-Extremity Amputation: A Systematic Review and Meta-Analysis.

BACKGROUND: Phantom limb pain (PLP) and symptomatic neuroma can be debilitating and significantly impact the quality of life of amputees. However, the prevalence of PLP and symptomatic neuromas in patients following dysvascular lower limb amputation (LLA) has not been reliably established. This systematic review and meta-analysis evaluates the prevalence and incidence of phantom limb pain and symptomatic neuroma after dysvascular LLA. METHODS: Four databases (Embase, MEDLINE, Cochrane Central, and Web of Science) were searched on October 5th, 2022. Prospective or retrospective observational cohort studies or cross-sectional studies reporting either the prevalence or incidence of phantom limb pain and/or symptomatic neuroma following dysvascular LLA were identified. Two reviewers independently conducted the screening, data extraction, and the risk of bias assessment according to the PRISMA guidelines. To estimate the prevalence of phantom limb pain, a meta-analysis using a random effects model was performed. RESULTS: Twelve articles were included in the quantitative analysis, including 1924 amputees. A meta-analysis demonstrated that 69% of patients after dysvascular LLA experience phantom limb pain (95% CI 53-86%). The reported pain intensity on a scale from 0-10 in LLA patients ranged between 2.3 ± 1.4 and 5.5 ± .7. A single study reported an incidence of symptomatic neuroma following dysvascular LLA of 5%. CONCLUSIONS: This meta-analysis demonstrates the high prevalence of phantom limb pain after dysvascular LLA. Given the often prolonged and disabling nature of neuropathic pain and the difficulties managing it, more consideration needs to be given to strategies to prevent it at the time of amputation.

Non degradation of chitosan and initial degradation of collagen nerve conduits used for protection of nerve coaptations.

BACKGROUND: Nerve conduits are either used to bridge nerve gaps of up to 3 cm or to protect nerve coaptations. Biodegradable nerve conduits, which are currently commercially available, include Chitosan or collagen-based ones. As histological aspects of their degradation are highly relevant for the progress of neuronal regeneration, the aim of this study was to report the histopathological signs of such nerve conduits, which were removed during revision surgery. MATERIALS AND METHODS: Either Chitosan (n = 2) or collagen (n = 2) nerve conduits were implanted after neuroma resection and nerve grafting (n = 2) or traumatic nerve lesion after cut (n = 1) or crush injury (n = 1) in two females and two men, aged between 17 and 57 years. Revision surgery with removal of the nerve conduits was indicated due to persisting neuropathic pain and sensorimotor deficits, limited joint motion, or neurolysis with hardware removal at a median time of 17 months (range: 5.5-48 months). Histopathological analyses of all removed nerve conduits were performed. RESULTS: A scar neuroma was diagnosed in one out of four patients. Mechanical complication occurred in one patient after nerve conduit implantation bridged over finger joints. Intraoperatively no or only initial signs of degradation of the nerve conduits were observed. Chitosan conduits revealed largely unchanged shape and structure of chitosan, and coating of the conduit by a vascularized fibrous membrane. The latter contained deposits taken up by macrophages, most likely representing dissolved chitosan. Characteristic histopathologic features of the degradation of collagen conduits were a disintegration of the compact collagen into separate fine circular strands, No foreign body reaction was observed in all removed nerve conduits. CONCLUSIONS: Both Chitosan nerve conduits have not been degraded. The collagen nerve conduits showed a beginning degradation process. Furthermore, wrapping the repaired nerve with a nerve conduit did neither prevent adhesions nor improved nerve gliding. Therefore, biodegradation in time should be particularly addressed in further developments of nerve conduits.

Surgery for internal rotation contracture in infancy may obviate the need for brachial plexus nerve reconstruction: early experience.

BACKGROUND: Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients; however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity. As a proof of concept, we report a highly selected subset of patients with BPBI in whom shoulder surgery undertaken before one year of age obviated the need for neuroma resection and nerve grafting. METHODS: A retrospective review was performed of all patients with upper trunk BPBI who underwent shoulder surgery before one year of age from 2015 to 2018. Upper extremity motor function was evaluated with preoperative and postoperative Active Movement Scale scores, Cookie tests, and the requirement for subsequent neuroma resection and nerve grafting. RESULTS: Fifteen patients with BPBI meeting the inclusion criteria underwent shoulder surgery (including a subscapularis slide and tendon transfers of the teres major and latissimus dorsi muscles) before 1 year of age. Preoperatively, no patients of the appropriate age passed the Cookie test for elbow flexion. Thirteen patients either passed the Cookie test or scored Active Movement Scale score 7 for elbow flexion at or before the last available follow-up undertaken at a median age of 3.4 [1.4, 5.2] years. One of those 13 patients underwent single fascicular distal nerve transfer to improve elbow flexion before subsequently passing the Cookie test. Two patients did not have sufficient follow-up to assess elbow flexion. CONCLUSION: Although the exact role of shoulder surgery in infancy for BPBI remains to be defined, the findings from this study provide proof of concept that early, targeted surgical treatment of the shoulder may obviate the need for brachial plexus nerve reconstruction in a highly selected group of infants with BPBI.

A Case of Superficial Papular Neuroma: A Rare Neural Neoplasm.

ABSTRACT: A case of 67-year-old male patient with superficial papular neuroma (SPN) on the occiput is reported. This is the second report of SPN and the first with clinical images. Histologically, in the superficial dermis and periadnexa, the specimen exhibits a nodule of bland spindle cells with an S-shaped and spindle nucleus, surrounded by eosinophilic collagen fibers and scattered mast cells, which forms focally peripheral nerve-like structures. Lichen simplex chronicus-like changes are observed. Immunostaining result revealed that the tumor cells are positive for S-100, neurofilament, collagen IV, and CD34 but negative for Melan A, epithelial membrane antigen, and glial fibrillary acidic protein. Histological differential diagnosis includes prurigo nodularis, neurotized nevus, benign peripheral nerve sheath tumor, such as neurofibroma or schwannoma, a type of neuroma, such as traumatic neuroma, mucosal neuroma, and palisaded encapsulated neuroma, or a type of neural hamartoma. A careful histological investigation will enable dermatopathologists to make a diagnosis of SPN.

Diagnosis of obstetric brachial plexus injury in a 2-year-old girl using high­frequency ultrasonography.

We describe an unusual case of infant obstetric brachial plexus injury located in the cervical (C)5-C6 brachial plexus nerve, which was preoperatively diagnosed using high-frequency ultrasonography (US) at 2 years of age. The girl was diagnosed with a right clavicular fracture because of shoulder dystocia. She had been showing movement limitations of her entire right upper limb after fracture healing and was then referred to our hospital at 2 years of age. High-frequency US showed that the roots of the right brachial plexus ran continuously, but the diameter of C6 was thinner on the affected side than on the contralateral side (right 0.12 cm vs. left 0.20 cm). A traumatic neuroma had formed at the upper trunk, which was thicker (diameter: right 0.35 cm vs. left 0.23 cm; cross-sectional area: right 0.65 cm2 vs. left 0.31 cm2) at the level of the supraclavicular fossa. Intraoperative findings were consistent with ultrasound findings. Postoperative pathology confirmed brachial plexus traumatic neuroma.

Systematic Review and Meta-Analysis of Global Neuroma Incidence in Upper Extremity Amputees.

BACKGROUND: Neuromas substantially decrease a patient's quality of life and obstruct the use of prosthetics. This systematic review and meta-analysis aimed to determine the global incidence of neuroma formation in upper extremity amputees. METHODS: A literature search was performed using 3 databases: Web of Science, MEDLINE, and Cochrane. Inclusion criteria for the systematic review were those studies investigating only upper extremity amputees and reported postamputation neuroma. A random-effects, inverse-variance analysis was conducted to determine the pooled proportion of neuromas within the upper extremity amputation population. Critical appraisal using the JBI Checklist for Studies Reporting Prevalence Data of each individual article were performed for the systematic review. RESULTS: Eleven studies met the inclusion criteria collating a total of 1931 patients across 8 countries. More than three-fourth of patients are young men (77%; age range, 19-54 years) and had an amputation due to trauma. The random-effects analysis found the pooled combined proportion of neuromas to be 13% (95% confidence interval, 8%-18%). The treatment of neuroma is highly variable, with some patients receiving no treatment. CONCLUSIONS: The pooled proportion of neuroma incidence in the 1931 patients was 13%. With the known global prevalence of upper extremity amputees, this translates to nearly 3 million amputees suffering from a neuroma globally. Increasing training in preventative surgical methods could contribute to lowering this incidence and improving the outcomes of this patient population.