Active nerve management for above the knee amputation: A comparison of through the wound versus posterior approach.

Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) are used to prevent or treat neuromas in amputees. TMR for above-the-knee amputation (AKA) is most commonly performed through a posterior incision rather than the stump wound because recipient motor nerves are primarily located in the proximal third of the thigh. When preventative TMR is performed with concurrent AKA, a posterior approach requires intraoperative repositioning and an additional incision. The purpose of this study was to evaluate feasibility of TMR and operative times for nerve management performed through the wound compared to a posterior approach in AKA patients to guide surgical decision-making. Patients who underwent AKA with TMR between 2018-2023 were reviewed. Patients were divided into two groups: TMR performed through the wound (Group I) and TMR performed through a posterior approach (Group II). If a nerve was unable to undergo coaptation for TMR due to the lack of suitable donor motor nerves, RPNI was performed. Eighteen patients underwent AKA with nerve management were included from Group I (8 patients) and Group II (10 patients). TMR coaptations performed on distinct nerves was 1.5 ± 0.5 in Group I compared to 2.6 ± 0.5 in Group II (p = 0.001). Operative time for Group I was 200.7 ± 33.4 min compared to 326.5 ± 37.1 min in Group II (p = 0.001). TMR performed through the wound following AKA requires less operative time than a posterior approach. However, since recipient motor nerves are not consistently found near the stump, RPNI may be required with TMR whereas the posterior approach allows for more TMR coaptations.

[Bionic Surgery Meets Bionic Reconstruction - First In-human use of Robotic Microsurgery in Targeted Muscle Reinnervation]. / Bionische Chirurgie trifft Bionische Rekonstruktion ­ erstes in-human Projekt von robotischer Mikrochirurgie zur Targeted Muscle Reinnervation.

Robotic microsurgery is an emerging field in reconstructive surgery, which provides benefits such as improved precision, optimal ergonomics, and reduced tremors. However, only a few robotic platforms are available for performing microsurgical procedures, and successful nerve coaptation is still a challenge. Targeted muscle reinnervation (TMR) is an innovative reconstructive procedure that rewires multiple nerves to remnant stump muscles, thereby reducing neuroma and phantom limb pain and improving the control of bionic prostheses. The precision of surgical techniques is critical in reducing axonal sprouting around the coaptation site to minimise the potential for neuroma formation. This study reports the first use of a microsurgical robotic platform for multiple nerve transfers in a patient undergoing TMR for bionic extremity reconstruction. The Symani robotic platform, combined with external microscope magnification, was successfully used, and precise handling of nerve tissue and coaptation was easily feasible even in anatomically challenging environments. While the precision and stability offered by robotic assistance may be especially useful for nerve surgery, the high economic costs of robotic microsurgery remain a major challenge for current healthcare systems. In conclusion, this study demonstrated the feasibility of using a robotic microsurgical platform for nerve surgery and transfers, where precise handling of tissue is crucial and limited space is available. Future studies will explore the full potential of robotic microsurgery in the future.

[Prosthetic Fitting Concepts after Major Amputation in the Upper Limb - an Overview of Current Possibilities]. / Prothetische Versorgungskonzepte nach Majoramputation der oberen Extremität ­ eine Übersicht gegenwärtiger Möglichkeiten.

BACKGROUND: The upper extremity and particularly the hands are crucial for patients in interacting with their environment, therefore amputations or severe damage with loss of hand function significantly impact their quality of life. In cases where biological reconstruction is not feasible or does not lead to sufficient success, bionic reconstruction plays a key role in patient care. Classical myoelectric prostheses are controlled using two signals derived from surface electrodes in the area of the stump muscles. Prosthesis control, especially in high amputations, is then limited and cumbersome. The surgical technique of Targeted Muscle Reinnervation (TMR) offers an innovative solution: The major arm nerves that have lost their target organs due to amputation are rerouted to muscles in the stump area. This enables the establishment of cognitive control signals that allow significantly improved prosthesis control. PATIENTS/MATERIALS AND METHODS: A selective literature review on TMR and bionic reconstruction was conducted, incorporating relevant articles and discussing them considering the clinical experience of our research group. Additionally, a clinical case is presented. RESULTS: Bionic reconstruction combined with Targeted Muscle Reinnervation enables intuitive prosthetic control with simultaneous movement of various prosthetic degrees of freedom and the treatment of neuroma and phantom limb pain. Long-term success requires a high level of patient compliance and intensive signal training during the prosthetic rehabilitation phase. Despite technological advances, challenges persist, especially in enhancing signal transmission and integrating natural sensory feedback into bionic prostheses. CONCLUSION: TMR surgery represents a significant advancement in the bionic care of amputees. Employing selective nerve transfers for signal multiplication and amplification, opens up possibilities for improving myoelectric prosthesis function and thus enhancing patient care. Advances in the area of external prosthetic components, improvements in the skeletal connection due to osseointegration and more fluid signal transmission using wireless, fully implanted electrode systems will lead to significant progress in bionic reconstruction, both in terms of precision of movement and embodiment.

[The surgical treatment of peripheral neuromas]. / De chirurgische behandeling van perifere neuromen.

Peripheral neuromas are a prevalent problem following nerve injury or certain surgical interventions like limb amputation. It is important to consider a peripheral neuroma when a patient experiences pain in the innervation area of a peripheral sensory or mixed nerve (branch), especially following trauma or amputation. Adequate recognition of a painful neuroma is crucial to treat patients satisfactorily for their invalidating and chronic symptoms. We want to emphasize that surgical intervention can be an effective and permanent treatment for symptomatic neuromas. The standard surgical treatment is neuroma excision and burying of the nerve stump in adjacent muscle. However, there is a shift towards new and active techniques like Targeted Muscle Reinnervation, of which future comparative research will have to demonstrate whether it is more effective in treating peripheral neuroma pain than conventional surgery.

[The surgical treatment of peripheral neuromas]. / De chirurgische behandeling van perifere neuromen.

Peripheral neuromas are a prevalent problem following nerve injury or certain surgical interventions like limb amputation. It is important to consider a peripheral neuroma when a patient experiences pain in the innervation area of a peripheral sensory or mixed nerve (branch), especially following trauma or amputation. Adequate recognition of a painful neuroma is crucial to treat patients satisfactorily for their invalidating and chronic symptoms. We want to emphasize that surgical intervention can be an effective and permanent treatment for symptomatic neuromas. The standard surgical treatment is neuroma excision and burying of the nerve stump in adjacent muscle. However, there is a shift towards new and active techniques like Targeted Muscle Reinnervation, of which future comparative research will have to demonstrate whether it is more effective in treating peripheral neuroma pain than conventional surgery.

Update on Upper Limb Neuroma Management.

Painful terminal neuromas in the upper limb due to nerve injury are common. Neuroma symptoms include a sharp and burning sensation, cold intolerance, dysesthesia, pain, numbness, and paresthesia. These symptoms could have a negative impact on the functional ability of the patient and quality of life. In addition, Prostheses use might be abandoned by amputees due to neuroma-induced pain. Many clinicians face challenges while managing neuromas. Contemporary "active" methods like regenerative peripheral nerve interface (RPNI), targeted muscle reinnervation (TMR), and processed nerve allograft repair (PNA) are replacing the conventional "passive" approaches such as excision, transposition, and implantation techniques. RPNI involves inducing axonal sprouting by transplanting the free end of a peripheral nerve into a free muscle graft. TMR includes reassigning the role of the peripheral nerve by the transfer of the distal end of a pure sensory or a mixed peripheral nerve to a motor nerve of a nearby muscle segment. To give the peripheral nerve a pathway to re-innervate its target tissue, PNA entails implanting a sterile extracellular matrix prepared from decellularized and regenerated human nerve tissue with preserved epineurium and fascicles. Of these, RPNI and TMR appear to hold a promising treatment for nerve-ending neuromas and prevent their relapse. In contrast, PNA may reduce neuroma pain and allow meaningful nerve repair. The aim of this article is to provide an overview of the newer approaches of TMR, RPNI, and PNA and discuss their implications, surgical techniques, and reported consequences.

Incidence and Nerve Distribution of Symptomatic Neuromas and Phantom Limb Pain after Below-Knee Amputation.

BACKGROUND: Patients with major lower limb amputations suffer from symptomatic neuromas and phantom-limb pain due to their transected nerves. Peripheral nerve surgery techniques, such as targeted muscle reinnervation and regenerative peripheral nerve interface, aim to physiologically prevent this nerve-specific pain. No studies have specifically reported on which nerves most frequently cause chronic pain. The authors studied the nerve-specific incidence of symptomatic neuroma formation and phantom limb pain in patients undergoing a below-knee amputation, to better tailor use of targeted muscle reinnervation and regenerative peripheral nerve interface. METHODS: This was a retrospective review of all patients undergoing a below-knee amputation from January 1, 2013, to December 31, 2018, at MedStar Georgetown University Hospital. All below-knee amputations were performed with a posterior skin flap, myotenodesis, and traction neurectomies of all nerves. Postoperative notes were reviewed for the presence of a symptomatic neuroma, defined as localized pain and a Tinel sign over a known sensory nerve, and nerve-specific phantom limb pain, defined as pain of the missing limb corresponding to a known dermatome. RESULTS: One hundred ninety-eight patients were included in this study. The rate of symptomatic neuroma formation was 14.6 percent (29 of 198), with the superficial peroneal and saphenous nerves most often involved. Diabetes and obesity were protective against symptomatic neuroma formation. The rate of nerve-specific phantom limb pain was 12.6 percent (25 of 198) and highly correlated with the presence of a symptomatic neuroma. CONCLUSION: To optimize outcomes for amputees, it is critical that surgeons best understand what nerves are more likely to form symptomatic neuromas and lead to nerve-specific phantom limb pain, so that surgeons can best tailor primary or secondary management of the major sensory nerves. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Techniques to prevent symptomatic neuroma in digital amputations.

The occurrence of a symptomatic neuroma on a digital amputation stump, whether traumatic or not, is a frequent complication that affects the patient's quality of life. The objective of this study was to analyze the complications inherent to the various techniques used to manage the nerves when performing digital amputation. We compared different surgical nerve management techniques to determine if one technique is more effective than another in preventing neuroma occurrence. We reviewed 105 patients over a 5-year period. A DN4 score greater than 4 and the modified Tinel test (percussion) showing a trigger zone allowed us to clinically diagnose symptomatic neuroma-related pain. We found 23 symptomatic neuromas out of 131 digital amputations. Twelve neuromas were found when the nerves had been neglected (12/33), eight were found in nerves treated by stripping (8/60), three when nerves were treated by stripping and thermal ablation (3/18). No neuroma was found in the five cases of centrocentral union of the two proper palmar digital nerves, in the 5 nerves buried in the bone or in the 9 nerves subjected to thermal ablation only. Management of the nerve is essential for the prevention of neuromas in digital amputations. New techniques such as bone burial and centrocentral union of the two stumps appear to be particularly effective.

Challenges and Potential in Targeted Muscle Reinnervation in Pediatric Amputees.

Targeted muscle reinnervation (TMR) is a powerful new tool in preventing and treating residual limb and phantom limb pain. In the adult population, TMR is rapidly becoming standard of care; however, there is a paucity of literature regarding indications and outcomes of TMR in the pediatric population. We present 2 cases of pediatric patients who sustained amputations and the relevant challenges associated with TMR in their cases. One is a 7-year-old patient who developed severe phantom and residual limb pain after a posttraumatic above-knee amputation. He failed pharmacologic measures and underwent TMR. He obtained complete relief of his symptoms and is continuing to do well 1.5 years postoperatively. The other is a 2-year-old boy with bilateral wrist and below-knee amputations as sequelae of sepsis. TMR was not performed because the patient never demonstrated evidence of phantom limb pain or symptomatic neuroma formation. We use these 2 cases to explore the challenges particular to pediatric patients when considering treatment with TMR, including capacity to report pain, risks of anesthesia, and cortical plasticity. These issues will be critical in determining how TMR will be applied to pediatric patients.

Targeted Muscle Reinnervation Improves Pain and Ambulation Outcomes in Highly Comorbid Amputees.

BACKGROUND: Approximately 200,000 people undergo a lower extremity amputation each year. Following amputation, patients suffer from chronic pain, inability to ambulate, and high mortality rates. Targeted muscle reinnervation is a nerve transfer procedure that redirects transected sensory and mixed nerves into motor nerves to treat neuroma and phantom limb pain. This study evaluates outcomes with prophylactic targeted muscle reinnervation at the time of below-knee amputation. METHODS: This is a cohort study comparing 100 patients undergoing below-knee amputation with primary targeted muscle reinnervation and 100 patients undergoing below-knee amputation with standard traction neurectomy and muscle implantation. Outcome metrics included the presence of residual and phantom limb pain, pain severity, opioid use, ambulation ability, and mortality rates. RESULTS: The targeted muscle reinnervation group was on average 60 years old with a body mass index of 29 kg/m2. Eighty-four percent had diabetes, 55 percent had peripheral vascular disease, and 43 percent had end-stage renal disease. Average follow-up was 9.6 months for the targeted muscle reinnervation group and 18.5 months for the nontargeted muscle reinnervation group. Seventy-one percent of targeted muscle reinnervation patients were pain free, compared with 36 percent (p < 0.01). Fourteen percent of targeted muscle reinnervation patients had residual limb pain, compared with 57 percent (p < 0.01). Nineteen percent of targeted muscle reinnervation patients had phantom limb pain, compared with 47 percent (p < 0.01). Six percent of targeted muscle reinnervation patients were on opioids, compared with 26 percent (p < 0.01); and 90.9 percent of targeted muscle reinnervation patients were ambulatory, compared with 70.5 percent (p < 0.01). CONCLUSION: Targeted muscle reinnervation reduces pain and improves ambulation in patients undergoing below-knee amputation, which may be critical in improving morbidity and mortality rates in this comorbid patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Surgical and technological advances in the management of upper limb amputees.

Upper limb amputations, ranging from transhumeral to partial hand, can be devastating for patients, their families, and society. Modern paradigm shifts have focused on reconstructive options after upper extremity limb loss, rather than considering the amputation an ablative procedure. Surgical advancements such as targeted muscle reinnervation and regenerative peripheral nerve interface, in combination with technological development of modern prosthetics, have expanded options for patients after amputation. In the near future, advances such as osseointegration, implantable myoelectric sensors, and implantable nerve cuffs may become more widely used and may expand the options for prosthetic integration, myoelectric signal detection, and restoration of sensation. This review summarizes the current advancements in surgical techniques and prosthetics for upper limb amputees. Cite this article: Bone Joint J 2021;103-B(3):430-439.

Targeted Muscle Reinnervation as a Solution for Nerve Pain.

LEARNING OBJECTIVES: After reading this article, the participants should be able to: 1. List current nonsurgical and surgical strategies for addressing postamputation neuroma pain and discuss their limitations. 2. Summarize the indications and rationale for targeted muscle reinnervation. 3. Develop an operative plan for targeted muscle reinnervation in an acute or delayed fashion for upper and lower extremity amputations. 4. Propose a management algorithm for treatment of symptomatic neuromas in an intact limb. 5. Discuss the risk of neuroma development after primary revision digital amputation or secondary surgery for a digital neuroma. 6. Compare and contrast targeted muscle reinnervation to the historical gold standard neuroma treatment of excision and burying the involved nerve in muscle, bone, or vein graft. 7. Interpret and discuss the evidence that targeted muscle reinnervation improves postamputation neuroma and phantom pain when performed either acutely or in a delayed fashion to treat existing pain. SUMMARY: Symptomatic injured nerves resulting from amputations, extremity trauma, or prior surgery are common and can decrease patient quality of life, thus necessitating an effective strategy for management. Targeted muscle reinnervation is a modern surgical strategy for prevention and treatment of neuroma pain that promotes nerve regeneration and healing rather than neuroma formation. Targeted muscle reinnervation involves the transfer of cut peripheral nerves to small motor nerves of adjacent, newly denervated segments of muscle and can be easily performed without specialized equipment. Targeted muscle reinnervation strategies exist for both upper and lower extremity amputations and for symptomatic neuromas of intact limbs. Targeted muscle reinnervation has been shown in a prospective, randomized, controlled trial to result in lower neuroma and phantom pain when compared to the historical gold standard of burying cut nerves in muscle.

Selective nerve root injection of ozone for the treatment of phantom limb pain: Three case reports.

RATIONALE: Phantom limb pain (PLP) refers to a common complication following amputation, which is characterized by intractable pain in the absent limb, phantom limb sensation, and stump pain. The definitive pathogenesis of PLP has not been fully understood, and the treatment of PLP is still a great challenge. Till now, ozone injection has never been reported for the treatment of PLP. PATIENT CONCERNS: We report 3 cases: a 68-year-old man, a 48-year-old woman, and a 46-year-old man. All of them had an amputation history and presented with stump pain, phantom limb sensation, and sharp pain in the phantom limb. Oral analgesics and local blocking in stump provided no benefits. DIAGNOSIS: They were diagnosed with PLP. INTERVENTIONS: We performed selective nerve root ozone injection combined with ozone injection in the stump tenderness points. OUTCOMES: There were no adverse effects. Postoperative, PLP, and stump pain were significantly improved. During the follow-up period, the pain was well controlled. LESSONS: Selective nerve root injection of ozone is safe and the outcomes were favorable. Ozone injection may be a new promising approach for treating PLP.

Targeted Muscle Reinnervation: Outcomes in Treating Chronic Pain Secondary to Extremity Amputation and Phantom Limb Syndrome.

BACKGROUND: Secondary to vascular disease, oncological resection, or devastating trauma, lower extremity amputations are performed globally at a yearly rate exceeding 1 million patients. Three-quarters of these patients will develop chronic pain or phantom pain, which presents a functional limitation for prosthetic use and contributes to deconditioning and increased mortality. Targeted muscle reinnervation (TMR) presents a surgical solution to this problem as either a primary or secondary intervention. METHODS: A review of the existing literature was conducted using a combination of the terms "phantom pain" "chronic pain," "neuroma," and "targeted muscle reinnervation" in Medline and PubMed. RESULTS: Five articles were found which addressed TMR for pain syndromes, four of which involved lower extremity amputation. Four of the articles were retrospective reviews, and one was a randomized control trial. A total of 149 patients were included, of which 82 underwent lower extremity amputation. Ninety-two of the patients underwent prophylactic TMR, of which 57 were secondary procedures.In patients who underwent TMR at the time of amputation, all studies reported a minimal development of symptomatic neuromas (27%). For secondary TMR, near-complete resolution of previous pain was found (90%). Phantom pain was noted to be similar to other studies in the literature but noted to improve over time with both primary (average drop of 3.5 out of 10 points on the numerical rating scale) and secondary (diminishing from 72% of patients to 13% over 6 months) operations. CONCLUSION: Although much of the current literature is limited to retrospective studies with few patients, these data point toward near-complete resolution of neuroma pain after treatment as well as complete prevention of chronic pain if TMR is used as a prophylactic measure during the index amputation. THIS STUDY WAS A LEVEL OF EVIDENCE IV: .

Outcomes, Challenges, and Pitfalls after Targeted Muscle Reinnervation in High-Level Amputees: Is It Worth the Effort?

BACKGROUND: Although the distal targets have been lost in proximal upper limb amputees, the neural signals for intuitive hand and arm function are still available and thus can be incorporated into more useful prosthetic function using targeted muscle reinnervation technique. In this article, the authors present their outcomes and range of indications in addition to experiences and pitfalls after 30 targeted muscle reinnervation cases at above-elbow and shoulder disarticulation level of amputation. METHODS: Thirty patients with above-elbow or shoulder disarticulation amputations were enrolled between 2012 and 2017. Indications for targeted muscle reinnervation surgery differed between improvement of prosthetic function (n = 19) and/or pain (n = 11). Functional outcome was evaluated with the Action Research Arm Test, the Southampton Hand Assessment Procedure, and the Clothespin-Relocation Test. Functional evaluation was performed at least at 6 months after final prosthetic fitting. RESULTS: All nerve transfers were successful and provided independent myoelectric signals. The 10 patients available for final functional evaluation showed Action Research Arm Test scores of 20.4 ± 1.9 and Southampton Hand Assessment Procedure scores of 40.5 ± 8.1. The Clothespin-Relocation Test showed a mean time of 34.3 ± 14.4 seconds. CONCLUSIONS: Targeted muscle reinnervation has improved prosthetic control and revolutionized neuroma treatment in upper limb amputees. Still, the rate of abandonment even after targeted muscle reinnervation surgery has been shown high, and several advances within the biotechnological interface will be needed to improve prosthetic function and acceptance in these patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Pedicled Serratus Anterior Flap as an Alternative Muscle Target for Targeted Muscle Reinnervation in Transhumeral Amputees.

Upper limb amputation is a universally devastating injury that results in substantial loss of function. Myoelectric prostheses represent a new generation of battery-powered programmable prostheses controlled by EMG signals. The aim of upper limb targeted muscle reinnervation (TMR) is to enhance the control of a myoelectric prosthesis by improving the number and quality of EMG signals that can be used to control prosthetic elbow, wrist, and hand movements. Current TMR techniques rely on preservation of parts of biceps and triceps to be used as reinnervated muscle targets. However, a subset of amputations exists in which the proximity or mechanism of injury results in loss of these local muscle targets, making these techniques less suitable. Alternative muscles beyond the zone of injury must be sought and imported as targets for residual nerves. Through its neurovascular anatomy and physical structure, the serratus anterior offers multiple potential targets in close vicinity to the upper limb, making the creation of additional signals through a single flap achievable in this challenging scenario. We present our technique using a pedicled serratus anterior muscle flap as an alternative muscle target in transhumeral amputees undergoing TMR.

Síndrome de la mama fantasma posmastectomía. Estudio de prevalencia y características clínicas en un hospital de tercer nivel / Post-mastectomy phantom breast syndrome. Study of prevalence and clinical characteristics in a tertiary hospital

Objetivo: Conocer la prevalencia y características del síndrome de la mama fantasma en nuestro entorno. Pacientes y métodos: Se realizó una encuesta telefónica a 50 mujeres mastectomizadas entre los años 2002 y 2009 en el Hospital General Universitario de Castellón. Se preguntó sobre la presencia de dolor antes del diagnóstico de la enfermedad y de la cirugía, del síndrome de dolor posmastectomía y del síndrome de la mama fantasma, ampliando el interrogatorio en caso de respuesta afirmativa para conocer las características de la sintomatología, el momento de aparición, la frecuencia de aparición, la duración de la clínica y la necesidad o no de tratamiento farmacológico específico en cada síndrome. Se realizó un análisis descriptivo de los datos obtenidos. Resultados: El 76% de las mujeres interrogadas presentaron algún tipo de sensación extraña o dolorosa en la zona de la cicatriz mamaria, de las cuales el 65,8% presentó sensaciones no dolorosas y el 34,2% dolorosas. El síndrome de la mama fantasma apareció en el 38% de las mujeres interrogadas, y en muchos de los casos (31,6%) de las que respondieron afirmativamente se expresaba en forma de picor en el pezón ausente. Conclusiones: El síndrome de dolor posmastectomía y el síndrome de la mama fantasma son entidades poco conocidas, aunque prevalentes en nuestro medio. Tienen un carácter complejo y multifactorial, por lo que es importante conocerlas para conseguir un correcto tratamiento de las pacientes afectas, y así mejorar su calidad de vida

Objective: To determine the prevalence of post-mastectomy pain syndrome and phantom breast syndrome in our environment. Patients and methods: We performed a telephone survey of 50 women who underwent mastectomy between 2002 and 2009 in the General Hospital of Castellon (Spain). The women were asked about the presence of pain before diagnosis of the disease and surgery, post-mastectomy pain syndrome, and phantom breast syndrome. Women with symptoms were asked about their characteristics, time of onset, frequency, duration, and whether or not a specific pharmacological treatment was needed for each syndrome. A descriptive analysis was performed of the data obtained. Results: A total of 76% of the women surveyed had some kind of strange or painful sensation in the breast scar, 65.8% of whom had painless sensations and 34.2% had painful sensations. Phantom breast syndrome appeared in 38% of the surveyed women and manifested as an itch in the absent nipple in 31.6% of the women. Conclusions: Post-mastectomy pain syndrome and phantom breast syndrome are little known entities, although they prevalent in our environment. These syndromes are complex and multifactorial; therefore, familiarity with their characteristics is essential to provide affected women with proper treatment and improve their quality of life

Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain.

BACKGROUND: Postamputation pain affects a large number of individuals living with major limb loss. Regenerative peripheral nerve interfaces are constructs composed of a transected peripheral nerve implanted into an autologous free muscle graft. The authors have previously shown that regenerative peripheral nerve interfaces can be used to treat symptomatic end neuromas that develop after major limb amputation. In this study, they investigated the potential of prophylactic interfaces to prevent the formation of symptomatic neuromas and mitigate phantom limb pain. METHODS: Patients who underwent limb amputation with and without prophylactic regenerative peripheral nerve interface implantation were identified. A retrospective review was performed to ascertain patient demographics, level of amputation, and postoperative complications. Documentation of symptomatic neuromas and phantom limb pain was noted. RESULTS: Postoperative outcomes were evaluated in a total of 90 patients. Forty-five patients underwent interface implantation at the time of primary amputation, and 45 control patients underwent amputation without interfaces. Six control patients (13.3 percent) developed symptomatic neuromas in the postoperative period compared with zero (0.0 percent) in the prophylactic interface group (p = 0.026). Twenty-three interface patients (51.1 percent) reported phantom limb pain, compared with 41 control patients (91.1 percent; p < 0.0001). CONCLUSIONS: Prophylactic regenerative peripheral nerve interfaces in major limb amputees resulted in a lower incidence of both symptomatic neuromas and phantom limb pain compared with control patients undergoing amputation without regenerative peripheral nerve interfaces, suggesting that prevention of peripheral neuromas following amputation may diminish the central pain mechanisms that lead to phantom limb pain. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.