Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

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.

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.

Targeted Muscle Reinnervation to Reduce Postoperative Pain in Patients Undergoing Hindquarter Resections.

BACKGROUND/AIM: Pre-emptive targeted muscle reinnervation (TMR) at the time of amputation results in less phantom limb pain (PLP) compared with untreated amputee controls. There is limited literature describing the technique in patients undergoing hindquarter amputation despite up to 90% of these patients reporting PLP and 50% presenting with painful neuroma. The purpose of the current study was to describe the motor nerves accessible through a primary hind-quarter amputation to be used for TMR and review pain outcomes in clinical case correlates of patients with TMR. PATIENTS AND METHODS: Six limbs were obtained from three fresh adult cadavers and proximal sensory and motor nerves were dissected. A review of patients undergoing hindquarter amputation with TMR was conducted. RESULTS: Transfers for the sciatic, femoral, and obturator nerves were identified in cadavers. In reviews of patients, they were taking narcotic and neuro-leptic pain medication for a mean of 23 days and 168 days. At most recent follow-up, no patient reported debilitating phantom pain nor pain associated with neuromas. CONCLUSION: Given the positive preliminary results in our study group as well as the accessible neuroanatomy, pre-emptive TMR should be considered at the time of surgery to limit PLP and dependence on pain medications.

Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial.

BACKGROUND: Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation - commonly known as neuroma pain - and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP. METHODS: One hundred ten upper and lower limb amputees suffering from RLP will be recruited and assigned randomly to one of the surgical interventions (TMR, RPNI, or neuroma transposition) in an equal allocation ratio. Complete evaluations will be performed during a baseline period prior to the surgical intervention, and follow-ups will be conducted in short term (1, 3, 6, and 12 months post-surgery) and in long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participant is unsatisfied with the outcome of the treatment at that time, further treatment including one of the other procedures will be discussed in consultation with the clinical investigator at that site. DISCUSSION: A double-blind RCT is necessary for the establishment of evidence-based procedures, hence the motivation for this work. In addition, studies on pain are challenging due to the subjectivity of the experience and the lack of objective evaluation methods. Here, we mitigate this problem by including different pain evaluation methods known to have clinical relevance. We plan to analyse the primary variable, mean change in NRS (0-10) between baseline and the 12-month follow-up, using the intention-to-treat (ITT) approach to minimise bias and keep the advantage of randomisation. The secondary outcomes will be analysed on both ITT and per-protocol (PP). An adherence protocol (PP population) analysis will be used for estimating a more realistic effect of treatment. TRIAL REGISTRATION: ClincialTrials.gov NCT05009394.

The Current State of Targeted Muscle Reinnervation: A Systematic Review.

BACKGROUND: Targeted muscle reinnervation (TMR) is growing in popularity; however, literature evaluating patient characteristics and outcomes is limited. METHODS: The EMBASE database was queried with the search terms "targeted muscle reinnervation" OR "TMR" AND "outcomes" OR "patient outcomes." Clinical human studies in English were eligible for inclusion, yielding 89 articles. After rigorous exclusion criteria, a total of 13 articles were included in this review. Study data including geographic location, patient demographics, TMR indication, amputation level, number of nerve transfers performed, length of follow-up, and reported outcomes were extracted and analyzed. RESULTS: The included articles represent 338 patients (341 limbs). Average patient age was 47.4 years. Indication for amputation included trauma (n = 125), infection (n = 76) cancer/tumor resection (n = 71), ischemia (n = 18), failed Charcot reconstruction (n = 15), failed hardware (n = 9), burn (n = 4), and CRPS (n = 4). Five studies included upper extremity TMR only, two included lower extremity TMR only, and six included both upper and lower extremity TMR. TMR was performed in an immediate or delayed fashion, with an average of 2.2 nerve transfers performed per limb overall. Average length of follow-up was 22.3 months. In three studies, patients with phantom limb pain undergoing delayed TMR were found to have significant or trending toward significant reduction in pain after TMR using numeric rating scale and patient-reported outcomes measurement information system scales. One article reported 9/10 patients with improved or complete resolution of phantom limb pain after delayed TMR. Three studies found that patients undergoing immediate TMR had lower pain scores compared with non-TMR controls. CONCLUSION: While there is evidence that TMR reduces neuroma-related pain and improves the quality of life for amputees, further outcomes studies are needed to study the patient experience with TMR on a larger scale. Establishing standardized, validated patient-reported outcomes assessment tools is critical to future investigation in this field.

Targeted muscle reinnervation: a brief history of a promising procedure for effective management of amputation pain.

Each year, 27.5% of the 150 000 people in the United States who require lower extremity amputation experience significant postoperative complications, including pain, infection, and need for reoperation. Postamputation pain, including RLP and PLP, is debilitating. While the causes of such pain remain unknown, neuroma formation following sensory nerve transection is believed to be a major contributor. Various techniques exist for management of a symptomatic neuroma, but few data exist on which technique is superior. Furthermore, there are few data on primary prevention of neuroma formation following injury or intentional transection. The TMR technique shows promise for both management of PLP and RLP and prevention of neuroma formation. Following amputation, transected sensory nerves are coapted to nearby motor nerve supplying remaining extremity musculature. Not only does this procedure generate increased myoelectric signals for improved prosthesis control, TMR appears to neurophysiologically alter sensory nerves, preventing formation of painful sensory neuromas. The sole RCT to date evaluating the efficacy of TMR showed statistically significant reduction in PLP. TMR is not limited to use in the setting of major limb amputation. It has also been used in the setting of post-mastectomy pain, abdominal wall neuromas, digital amputations, and headache surgeries. This article reviews the origin of TMR and provides a brief description of histologic changes following the procedure, as well as current data regarding the efficacy of TMR with regard to postoperative pain relief. It also seeks to provide a concise, comprehensive resource for providers to facilitate better discussions with patients about treatment options.

Peripheral Nerve Management in Extremity Amputations.

The effective management of peripheral nerves in amputation surgery is critical to optimizing patient outcomes. Nerve-related pain after amputation is common, maybe a source of dissatisfaction and functional impairment, and should be considered in all amputees presenting with pain and dysfunction. While traction neurectomy or transposition has long been the standard of care, both regenerative peripheral nerve interface (RPNI) and targeted muscle reinnervation (TMR) have emerged as promising techniques to improve neuroma-related and phantom pain. A multi-disciplinary and multi-modal approach is essential for the optimal management of amputees both acutely and in the delayed or chronic setting.

Complex regional pain syndrome patient treated with a below knee amputation, implanting nerves directly into muscle: A case report.

Persistent, disabling lower extremity pain, outside the distribution of a single nerve, is termed chronic regional pain syndrome (CRPS), but, in reality, this chronic pain is often due to multiple peripheral nerve injuries. It is the purpose of this report to describe the first application of the "traditional," nerve implantation into muscle, usually used in the treatment of a painful neuroma, as a pre-emptive surgical technique in doing a below knee amputation (BKA). In 2011, a 51-year-old woman developed severe, disabling CRPS, after a series of operations to treat an enchondroma of the left fifth metatarsal. When appropriate peripheral nerve surgeries failed to relieve distal pain, a BKA was elected. The approach to the BKA included implantation of each transected peripheral nerve directly into an adjacent muscle. At 5.0 years after the patient's BKA, the woman reported full use of this extremity, using the prosthesis, and was free of phantom limb and residual limb pain. This anecdotal experience gives insight that long-term relief of lower extremity CRPS can be achieved by a traditional BKA utilizing the approach of implanting each transected nerve into an adjacent muscle.

Targeted Muscle Reinnervation (TMR) and Other Considerations in Upper Extremity Amputation.

Targeted muscle reinnervation (TMR) is a procedure in which amputated nerves are transferred to motor branches of functionally expendable muscles, which can then serve as "biological amplifiers" of neurologic information. It is a technique that was developed with the primary intent of improving myoelectric prosthesis control in high level upper extremity amputees. Over time, TMR has been shown to confer significant benefits in terms of both residual and phantom limb pain and as such has become a powerful tool in neuroma management in amputees and non-amputees. This review first discusses general principles of amputation management in the upper extremity, including the different types of prosthetics that are available for these patients. The history, rationale, and evolution of TMR will then be outlined, followed by several relevant surgical principles. Finally, the current evidence for and against TMR will be reviewed. Robust data on the functional benefits are still needed, and future studies will continue to clarify its role in both upper and lower extremity amputees.

[Targeted muscle reinnervation and targeted sensory reinnervation : Role of complex neurotization after amputation]. / "Targeted muscle reinnervation" und "targeted sensory reinnervation" : Rolle komplexer Neurotisationen nach Amputation.

In association with major amputations of the upper and lower extremities, surgical procedures with nerve transfer are increasingly being introduced. In order to examine the value of these procedures the currently available data were analyzed and related to the corresponding insights from conventional amputation surgery as well as confirmed aspects of microsurgery of peripheral nerves. Mainly retrospective observations of low case numbers and sometimes individually different surgical approaches can be found. Risk analysis and sufficient long-term follow-up periods are lacking as well as comparisons with appropriate control groups. The published results on operative procedures with selected nerve transfers after or during amputation do not currently allow any conclusions about the advantages. Systematic influences in the assessment of the results are probable. Implementation of these treatment options outside controlled clinical trials cannot be recommended.

A consecutive series of targeted muscle reinnervation (TMR) cases for relief of neuroma and phantom limb pain: UK perspective.

BACKGROUND: Studies have suggested that targeted muscle reinnervation (TMR) can improve symptoms of neuroma pain (NP) and phantom limb pain (PLP) in patients. OBJECTIVES: Our primary objective was to measure changes in NP and PLP levels following TMR surgery at 4-time points (baseline, 3, 6- and 12-months postoperatively). Secondary aims included identification of the character and rate of any surgical complications and patients' satisfaction with TMR. METHODS: A retrospective review of outcomes of 36 patients who underwent TMR surgery to treat intractable NP and/or PLP after major amputation of an upper (UL) or lower limb (LL) at a single centre in London, UK over 7 years. The surgical techniques, complications, and satisfaction with TMR are described. RESULTS: Forty TMR procedures were performed on 36 patients. Thirty patients had complete data for NP and PLP levels at all pre-defined time points. Significant improvements (p<0.01) in both types of pain were observed for both upper and LL amputees. However, there were varying patterns of recovery. For example, UL amputees experienced worsening of PLP in the first few months post-operatively whereas surgical complications were more common in LL cases. Patients were overwhelmingly satisfied with the improvements in their symptoms (90%). CONCLUSIONS: TMR surgery appeared to relieve both NP and PLP although the retrospective nature of this study limits the strength of this conclusion. However, complication rates were high, and it is crucial for surgeons and patients to fully understand the course and outcomes of this novel surgery prior to undertaking treatment.

Prevention is better than cure: Surgical methods for neuropathic pain prevention following amputation - A systematic review.

BACKGROUND: Pain after amputation can be known as residual limb pain (RLP) or phantom limb pain (PLP); however, both can be disabling in daily life with reported incidences of 8% for finger amputations and up to 85% for major limb amputations. The current treatment is focused on reducing the pain after neuropathic pain occurs. However, surgical techniques to prevent neuropathic pain after amputation are available and effective, but they are underutilized. The purpose of the review is to investigate the effects of techniques during amputation to prevent neuropathic pain. METHODS: A systematic review was performed in multiple databases (Embase, Medline, Web of Science, Scopus, Cochrane, and Google Scholar) and following the PRISMA guidelines. Studies that reported surgical techniques to prevent neuropathic pain during limb amputation were included. RESULTS: Of the 6188 selected studies, 13 eligible articles were selected. Five articles reported techniques for finger amputation: neurovascular island flap, centro-central union (CCU), and epineural ligatures, and flaps. For finger amputations, the use of prevention techniques resulted in a decrease of incidences from 8% to 0-3% with CCU being the most beneficial. For major limb amputations, the incidences for RLP were decreased to 0 to 55% with TMR and RPNI and compared to 64-91% for the control group. Eight articles reported techniques for amputations on major limbs: targeted muscle reinnervation (TMR), targeted nerve implantation, concomitant nerve coaptation, and regenerative peripheral nerve interface (RPNI). CONCLUSIONS: Based on the current literature, we state that during finger and major limb amputation, the techniques to prevent neuropathic pain and PLP should be performed.

Utilization of Techniques for Upper Extremity Amputation Neuroma Treatment and Prevention.

This study aimed to understand the current utilization of surgical approaches for nerve ending management in upper extremity amputation to prevent and treat nerve-related pain. We administered a survey to 190 of 1270 surgeons contacted by email (15% response rate) and analyzed their demographics, practice patterns, and perceptions regarding techniques for nerve ending management in upper extremity amputees. Although many surgical techniques were employed, most surgeons (54%) performed traction neurectomy during amputation and, alternatively, bury nerve into muscle if a neuroma subsequently develops (52%). Surgeons in practice less than 10 years were more likely to perform targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI) than surgeons in practice greater than 10 years (p<0.001). TMR and RPNI were performed more frequently for proximal amputations than distal amputations, but there is no consensus regarding the optimal timing to utilize these techniques. Surgeons commonly cited improved prosthetic control, pain, and phantom limb symptoms as reasons for performing TMR and RPNI. Increased physician compensation as a consideration was more commonly cited among TMR non-adopter than adopters (31% vs 14%, p=0.008). There is no consensus regarding techniques for the prevention or treatment of nerve ending pain in upper extremity amputees. TMR and RPNI are being utilized with increasing frequency and both patient and surgeon factors affect implementation in clinical practice.

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 for the Treatment of Neuroma.

Targeted muscle reinnervation (TMR) is the surgical rerouting of severed nerve endings to nearby expendable motor nerve branches. These nerve transfers provide a pathway for axonal growth, limiting the amputated nerve ends' disorganized attempt at regeneration that leads to neuroma formation. In the amputee population, TMR is successful in the treatment and prevention of chronic phantom limb pain and residual limb pain. In the nonamputee population, applications of TMR are ever expanding in the treatment of chronic neuroma pain owing to trauma, compression, or surgery. This article reviews the indications for TMR, preoperative evaluation, and various surgical techniques.

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.

Targeted Muscle Reinnervation and Osseointegration for Pain Relief and Prosthetic Arm Control in a Woman with Bilateral Proximal Upper Limb Amputation.

BACKGROUND: Bilateral proximal upper limb loss is a dramatic life-changing event. Replacement of the lost function with prosthetic arms, including multiple mechatronic joints, has remained a challenge from the control, comfort, and pain management perspectives. Targeted muscle reinnervation (TMR) is a peripheral nerve surgical procedure proposed to improve the intuitive control of the prosthetic arm and for neuroma and phantom pain management. Moreover, osseointegrated percutaneous implants (OPIs) allow for direct skeletal attachment of the prosthetic arm, ensuring freedom of movement to the patient's residual articulations. CASE DESCRIPTION: We have reported the first combined application of TMR and an OPI to treat a 24-year-old woman with a bilateral amputation at the shoulder level on the right side and at the very proximal transhumeral level on the left side. TMR was performed bilaterally in a single day, accounting for the peculiar patient's anatomy, as preparatory stage to placement of the OPI, and considering the future availability of implantable electromyographic sensors. The 2 OPI surgeries on the left side were completed after 8.5 months, and prosthetic treatment was completed 17 months after TMR. CONCLUSIONS: The use of TMR resolved the phantom pain bilaterally and the right-side neuroma pain. It had also substantially reduced the left side neuroma pain. The actual prosthetic control result was intuitive, although partially different from expectations. At 2 years after TMR, the patient reported improvement in essential activities of daily living, with a remarkable preference for the OPI prosthesis. Only 1 suspected case of superficial infection was noted, which had resolved. Overall, this combined treatment required a highly competent multidisciplinary team and exceptional commitment by the patient and her family.

Targeted Muscle Reinnervation Improves Residual Limb Pain, Phantom Limb Pain, and Limb Function: A Prospective Study of 33 Major Limb Amputees.

BACKGROUND: Targeted muscle reinnervation is an emerging surgical technique to treat neuroma pain whereby sensory and mixed motor nerves are transferred to nearby redundant motor nerve branches. In a recent randomized controlled trial, targeted muscle reinnervation was recently shown to reduce postamputation pain relative to conventional neuroma excision and muscle burying. QUESTIONS/PURPOSES: (1) Does targeted muscle reinnervation improve residual limb pain and phantom limb pain in the period before surgery to 1 year after surgery? (2) Does targeted muscle reinnervation improve Patient-reported Outcome Measurement System (PROMIS) pain intensity and pain interference scores at 1 year after surgery? (3) After 1 year, does targeted muscle reinnervation improve functional outcome scores (Orthotics Prosthetics User Survey [OPUS] with Rasch conversion and Neuro-Quality of Life [Neuro-QOL])? METHODS: Data on patients who were ineligible for randomization or declined to be randomized and underwent targeted muscle reinnervation for pain were gathered for the present analysis. Data were collected prospectively from 2013 to 2017. Forty-three patients were enrolled in the study, 10 of whom lacked 1-year follow-up, leaving 33 patients for analysis. The primary outcomes measured were the difference in residual limb and phantom limb pain before and 1 year after surgery, assessed by an 11-point numerical rating scale (NRS). Secondary outcomes were change in PROMIS pain measures and change in limb function, assessed by the OPUS Rasch for upper limbs and Neuro-QOL for lower limbs before and 1 year after surgery. RESULTS: By 1 year after targeted muscle reinnervation, NRS scores for residual limb pain from 6.4 ± 2.6 to 3.6 ± 2.2 (mean difference -2.7 [95% CI -4.2 to -1.3]; p < 0.001) and phantom limb pain decreased from 6.0 ± 3.1 to 3.6 ± 2.9 (mean difference -2.4 [95% CI -3.8 to -0.9]; p < 0.001). PROMIS pain intensity and pain interference scores improved with respect to residual limb and phantom limb pain (residual limb pain intensity: 53.4 ± 9.7 to 44.4 ± 7.9, mean difference -9.0 [95% CI -14.0 to -4.0]; residual limb pain interference: 60.4 ± 9.3 to 51.7 ± 8.2, mean difference -8.7 [95% CI -13.1 to -4.4]; phantom limb pain intensity: 49.3 ± 10.4 to 43.2 ± 9.3, mean difference -6.1 [95% CI -11.3 to -0.9]; phantom limb pain interference: 57.7 ± 10.4 to 50.8 ± 9.8, mean difference -6.9 [95% CI -12.1 to -1.7]; p ≤ 0.012 for all comparisons). On functional assessment, OPUS Rasch scores improved from 53.7 ± 3.4 to 56.4 ± 3.7 (mean difference +2.7 [95% CI 2.3 to 3.2]; p < 0.001) and Neuro-QOL scores improved from 32.9 ± 1.5 to 35.2 ± 1.6 (mean difference +2.3 [95% CI 1.8 to 2.9]; p < 0.001). CONCLUSIONS: Targeted muscle reinnervation demonstrates improvement in residual limb and phantom limb pain parameters in major limb amputees. It should be considered as a first-line surgical treatment option for chronic amputation-related pain in patients with major limb amputations. Additional investigation into the effect on function and quality of life should be performed. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Targeted Muscle Reinnervation in the Hand: Treatment and Prevention of Pain After Ray Amputation.

Targeted muscle reinnervation (TMR), originally developed as an experimental technique for prosthetic control, has been shown to be safe and effective for the treatment and prevention of postamputation pain. Targeted muscle reinnervation involves coaptation of residual nerve ends to nearby motor nerve branches of healthy but expendable muscles proximal to an amputation. It has been shown to prevent and reduce residual limb pain and phantom limb pain after major upper and lower extremity amputation. However, the use of this technique has not been described distal to the forearm because bioprosthetic use is not a consideration at that level. The aim of this article was to (1) present 2 cases of TMR performed in the setting of ray amputation, and (2) provide technical strategies for maximizing success and efficiency.