Acute versus non-acute targeted muscle reinnervation for pain control following major limb amputation: A comparative study.

BACKGROUND: Targeted muscle reinnervation (TMR) has been shown to reduce phantom limb pain (PLP) and residual limb pain (RLP) after major limb amputation. However, the effect of the timing of surgery on pain control and quality of life outcomes is controversial. We conducted a retrospective study to compare the outcomes of acute TMR for pain prevention with non-acute TMR for the treatment of established pain. METHODS: All patients treated with TMR in our institution between January 2018 and December 2021 were evaluated at 6, 12, 18 and 24 months post-operatively. Pain intensity and quality of life outcomes were assessed using the Brief Pain Inventory (Pain Severity and Pain Interference scales) and Pain Catastrophizing Scale. Outcomes were compared between acute and non-acute TMR using the Wilcoxon ranked-sum test or Fisher's exact test as appropriate. Multilevel mixed-effects linear regression was used to account for repeat measures and potential pain confounders. RESULTS: Thirty-two patients with 38 major limb amputations were included. Acute TMR patients reported significantly lower RLP and PLP scores, pain interference and pain catastrophisation at all time points (p < 0.05). Acute TMR was significantly associated with lower pain severity and pain interference in a linear mixed-effects model accounting for patient age, gender, amputation indication, amputation site, time post-TMR and repeated surveys (p < 0.05). There was no significant difference in the complication rate (p = 0.51). CONCLUSION: Acute TMR was associated with clinically and statistically significant pain outcomes that were better than that in non-acute TMR. This suggests that TMR should be performed with preventative intent, when possible, as part of a multidisciplinary approach to pain management, rather than deferred until the development of chronic pain.

The effectiveness of targeted muscle reinnervation in reducing pain and improving quality of life for patients following lower limb amputation.

BACKGROUND: Globally, over 1 million lower limb amputations are performed annually, with approximately 75% of patients experiencing significant pain, profoundly impacting their quality of life and functional capabilities. Targeted muscle reinnervation (TMR) has emerged as a surgical solution involving the rerouting of amputated nerves to specific muscle targets. Originally introduced to enhance signal amplification for myoelectric prosthesis control, TMR has expanded its applications to include neuroma management and pain relief. However, the literature assessing patient outcomes is lacking, specifically for lower limb amputees. This systematic review aims to assess the effectiveness of TMR in reducing pain and enhancing functional outcomes for patients who have undergone lower limb amputation. METHODS: A systematic review was performed by examining relevant studies between 2010 and 2023, focusing on pain reduction, functional outcomes and patient-reported quality of life measures. RESULTS: In total, 20 studies were eligible encompassing a total of 778 extremities, of which 75.06% (n = 584) were lower limb amputees. Average age was 46.66 years and patients were predominantly male (n = 70.67%). Seven studies (35%) reported functional outcomes. Patients who underwent primary TMR exhibited lower average patient-reported outcome measurement information system (PROMIS) scores for phantom limb pain (PLP) and residual limb pain (RLP). Secondary TMR led to improvements in PLP, RLP and general limb pain as indicated by average numeric rating scale and PROMIS scores. CONCLUSION: The systematic review underscores TMR's potential benefits in alleviating pain, fostering post-amputation rehabilitation and enhancing overall well-being for lower limb amputees.

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.

[Treatment and prevention phantom pain syndrome in mine-explosive injuries]. / Analiz ispol'zovaniya sovremennykh metodov lecheniya i profilaktiki fantomnogo bolevogo sindroma pri minno-vzryvnykh travmakh.

Phantom pain syndrome significantly impairs the quality of life and effectiveness of surgical treatment after limb amputations. The authors consider possible strategies for treatment and prevention in elective surgical intervention and mine-explosive injuries.

Chronic post amputation pain: pathophysiology and prevention options for a heterogenous phenomenon.

PURPOSE OF REVIEW: Chronic postamputation pain (cPAP) remains a clinical challenge, and current understanding places a high emphasis on prevention strategies. Unfortunately, there is still no evidence-based regimen to reliably prevent chronic pain after amputation. RECENT FINDINGS: Risk factors for the development of phantom limb pain have been proposed. Analgesic preventive interventions are numerous and no silver bullet has been found. Novel techniques such as neuromodulation and cryoablation have been proposed. Surgical techniques focusing on reimplantation of the injured nerve might reduce the incidence of phantom limb pain after surgery. SUMMARY: Phantom limb pain is a multifactorial process involving profound functional and structural changes in the peripheral and central nervous system. These changes interact with individual medical, psychosocial and genetic patient risk factors. The patient collective of amputees is very heterogeneous. Available evidence suggests that efforts should focus on prevention of phantom limb pain, since treatment is notoriously difficult. Questions as yet unanswered include the evidence-base of specific analgesic interventions, their optimal "window of opportunity" where they may be most effective, and whether patient stratification according to biopsychosocial risk factors can help guide preventive therapy.

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.

Assessment of efficiency of mirror therapy in preventing phantom limb pain in patients undergoing below-knee amputation surgery-a randomized clinical trial.

PURPOSE AND OBJECTIVES: Phantom limb pain (PLP) is a major cause of physical limitation and disability accounting for about 85% of amputated patients. Mirror therapy is used as a therapeutic modality for patients with phantom limb pain. Primary objective was to study the incidence of PLP at 6 months following below-knee amputation between the mirror therapy group and control group. METHODS: Patients posted for below-knee amputation surgery were randomized into two groups. Patients allocated to group M received mirror therapy in post-operative period. Two sessions of therapy were given per day for 7 days and each session lasted for 20 min. Patients who developed pain from the missing portion of the amputated limb were considered to have PLP. All patients were followed up for six months and the time of occurrence of PLP and intensity of the pain were recorded among other demographic factors. RESULTS: A total of 120 patients completed the study after recruitment. The demographic parameters were comparable between the two groups. Overall incidence of phantom limb pain was significantly higher in the control group (Group C) when compared to the mirror therapy (Group M) group [Group M = 7 (11.7%) vs Group C = 17 (28.3%); p = 0.022]. Intensity of PLP measured on the Numerical Rating Scale (NRS) was significantly lower at 3 months in Group M compared to Group C among patients who developed PLP [NRS - median (Inter quartile range): Group M 5 (4,5) vs Group C 6 (5,6); p 0.001]. CONCLUSION: Mirror therapy reduced the incidence of phantom limb pain when administered pre-emptively in patients undergoing amputation surgeries. The severity of the pain was also found to be lower at 3 months in patients who received pre-emptive mirror therapy. TRIAL REGISTRATION: This prospective study was registered in the clinical trial registry of India. TRIAL REGISTRATION NUMBER: CTRI/2020/07/026488.

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.

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.

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.

Systematic Review and Meta-Analysis of the Effect of Perineural Catheters in Major Lower Limb Amputations.

OBJECTIVE: Controlling pain after major lower limb amputation (MLLA) is of critical importance to patients and clinicians. The aim of this systematic review and meta-analysis was to assess the effect of perineural catheters (PNCs) on post-operative pain, post-operative morphine requirement, in-hospital mortality, long term phantom limb pain, and chronic stump pain. METHODS: A systematic review using PubMed, EMBASE via OVID and the Cochrane library from database inception (1946) to 20 October 2020 was performed according to PRISMA guidelines. Studies involving patients undergoing MLLA which reported on post-operative morphine requirement, pain scores, in-hospital mortality, phantom limb pain (PLP), and chronic stump pain were included. Studies comparing PNC use with epidural or wound site local anaesthetic infusions were excluded. Outcome data were extracted from individual studies and meta-analysis was performed using a random effects (Mantel-Haenszel) model for dichotomous data using an odds ratio (OR) summary statistic with 95% confidence intervals (CI), and with an inverse variance random effects model for continuous data using a standardised mean difference (SMD) summary statistic with 95% CIs. Sensitivity analyses were performed for post-operative pain scores and post-operative morphine requirement. Study quality was assessed using the Downs and Black score, and outcomes were assessed using the GRADE tool. RESULTS: Ten studies reporting on 731 patients were included, with 350 patients receiving a PNC and 381 receiving standard care. PNC use is associated with a reduction in post-operative pain (SMD -0.30, 95% CI -0.58 - -0.01, p = .040, I2 = 54%, GRADE quality of evidence: low) and post-operative morphine requirements (SMD -0.63, 95% CI -1.03 - -0.23, p = .002, I2 = 75%, GRADE quality of evidence: moderate), although the effect of PNC on reduced post-operative morphine requirements is lost on sensitivity analysis of randomised trials only (p = .40). No demonstrable effect was found on in-hospital mortality, PLP, or chronic stump pain (GRADE quality of evidence: low). CONCLUSION: PNC use in amputees is associated with a significant reduction in post-operative pain scores and post-operative morphine requirements, although this latter finding is lost on sensitivity analysis of randomised trials only.

Application of Spare Parts in Combination with Targeted Muscle Reinnervation Surgery.

SUMMARY: Targeted muscle reinnervation is a contemporary technique designed to enhance an amputee's ability to operate a myoelectric prosthesis. This technique has been shown to decrease neuropathic pain, including neuroma and phantom limb pain. In certain amputations, especially forequarter and hindlimb levels, there may be no nearby recipient muscle sites, or the residual nerve may be too short to perform targeted muscle reinnervation. Applying the spare parts concept can help solve this problem by providing nerve autograft or additional muscle recipient sites within the spare parts flap for successful targeted muscle reinnervation surgery procedures. A retrospective review of all patients that underwent spare parts targeted muscle reinnervation reconstructions between 2016 and 2019 at two institutions was performed. Patients were assessed for healing, neuroma and phantom limb pain, and function. Twelve patients underwent targeted muscle reinnervation during spare parts reconstruction; eight were male and four were female. The mean patient age was 55.3 years (range, 16 to 72 years). For those with known soft-tissue deficit size, the surface area of the donor site spared by using spare parts reconstruction ranged from 216 to 856 cm2. None of the 12 patients subsequently experienced neuroma, and 75 percent had no phantom limb pain after 3 months. Three patients have obtained insurance-approved myoelectric prosthetics, and all three demonstrated intuitive control of targeted muscles. Using a spare parts reconstruction in conjunction with targeted muscle reinnervation may optimize reconstructive efforts in the setting of major limb amputations and aid in decreasing phantom limb and neuroma pain, and facilitate the possibility of functional prosthetic and/or myoelectric prosthesis use. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Targeted muscle reinnervation following external hemipelvectomy or hip disarticulation: An anatomic description of technique and clinical case correlates.

BACKGROUND: Targeted muscle reinnervation (TMR) has been shown to decrease or prevent neuropathic pain, including phantom and residual limb pain, after extremity amputation. Currently, a paucity of data and lack of anatomical description exists regarding TMR in the setting of hemipelvectomy and/or hip disarticulations. We elaborate on the technique of TMR, illustrated through cadaveric and clinical correlates. METHODS: Cadaveric dissections of multiple transpelvic exposures were performed. The major mixed motor and sensory nerve branches were identified, dissected, and tagged. Amputated peripheral nerves were transferred to identified, labeled target motor nerves via direct end-to-end nerve coaptations per traditional TMR technique. A retrospective review was completed by our multi-institutional teams to include examples of clinical correlates for TMR performed in the setting of hemipelvectomies and hip disarticulations. RESULTS: A total of 12 TMR hemipelvectomy/hip disarticulation cases were performed over a 2 to 3-year period (2018-2020). Of these 12 cases, 9 were oncologic in nature, 2 were secondary to traumatic injury, and 1 was a failed limb salvage in the setting of chronic refractory osteomyelitis of the femoral shaft. CONCLUSIONS: This manuscript outlines the technical considerations for TMR in the setting of hemipelvectomy and hip disarticulation with supporting clinical case correlates.

Perioperative Anesthetic Techniques to Reduce Surgical Morbidity After Amputation.

Anesthetic modalities to mitigate the development of phantom limb pain have not been standardized into an evidence-based, multimodal anesthesia protocol to promote improved patient outcomes. This quality improvement project involved the implementation of a lower extremity, amputation-specific anesthesia protocol. In the postimplementation group, 94 patients were anesthetized for their amputation using an Amputation Improved Recovery Enhanced Recovery After Surgery (ERAS) protocol. Patient outcomes before and after protocol implementation were compared. The rate of continuous peripheral nerve block placement was higher in the postimplementation group (37.2%) than the preimplementation group (29.6%, P = .337). The 2 groups did not differ on average pain scores and morphine equivalent consumption rates per patient during hospitalization. The postimplementation group had significantly lower mean pain scores during the first 24 hours after amputation (P = .046); fewer postoperative complications (P = .001), amputation revisions (P = .003), 30-day hospital readmissions (P = .049), and readmissions related to amputation surgery (P = .019); and higher rates of early phantom limb pain that resolved during hospitalization (P = .012). Use of a standardized anesthetic protocol designed for patients undergoing amputation improved patient outcomes. Trials of this protocol elsewhere may contribute to improved recovery for patients undergoing amputations.

[Perioperative measures for prevention of phantom pain: an evidence-based approach to risk reduction]. / Perioperative Maßnahmen zur Prävention von Phantomschmerz: ein evidenzbasierter Ansatz zur Risikoreduktion.

Prevention of phantom limb pain is one of the biggest and still largely unsolved challenges in perioperative medicine. Despite many study efforts and optimization of postoperative pain treatment over the last 30 years, a significant reduction in the incidence of phantom limb pain has not been achieved. Current studies have also shown that at least 50% of patients develop phantom pain after 6 months. A possible approach could be to combine multiple synergistic interventions and implement them as a perioperative phantom pain management strategy bundle. In addition to regional anesthesia, NMDA antagonists, gabapentinoids, antidepressants and systemic lidocaine could play a relevant role. The aim of this pharmacological intervention was the modification of the pathophysiological changes in peripheral nerves and in the central nervous system after amputation.

Perineural local anaesthetic catheter after major lower limb amputation trial (PLACEMENT): results from a randomised controlled feasibility trial.

OBJECTIVES: To determine the feasibility of undertaking a randomised controlled effectiveness trial evaluating the use of a perineural catheter (PNC) after major lower limb amputation with postoperative pain as the primary outcome. DESIGN: Randomised controlled feasibility trial. SETTING: Two vascular Centres in South Wales, UK. PARTICIPANTS: 50 patients scheduled for major lower limb amputation (below or above knee) for complications of peripheral vascular disease. INTERVENTIONS: The treatment arm received a PNC placed adjacent to the sciatic or tibial nerve at the time of surgery, with continuous infusion of levobupivacaine hydrochloride 0.125% for up to 5 days. The control arm received neither local anaesthetic nor PNC. Both arms received usual perioperative anaesthesia and postoperative analgesia. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the proportion of eligible patients who were randomised and the proportion of recruited patients who provided primary effectiveness outcome data. Secondary outcomes were: the proportion of recruited patients reaching 2 and 6 month follow-up and supplying pain data; identification of key cost drivers; development of an economic analysis framework for a future effectiveness trial; identification of barriers to recruitment and site set-up; and identification of the best way to measure postoperative pain. RESULTS: Seventy-six of 103 screened patients were deemed eligible over a 10 month period. Fifty (64.5%) of these patients were randomised, with one excluded in the perioperative period. Forty-five (91.3%) of 49 recruited patients provided enough pain scores on a 4-point verbal rating scale to allow primary effectiveness outcome evaluation. Attrition rates were high; 18 patients supplied data at 6 month follow-up. Costs were dominated by length of hospital stay. Patients and healthcare professionals reported that trial processes were acceptable. CONCLUSIONS: Recruitment of patients into a trial comparing PNC use to usual care after major lower limb amputation with postoperative pain measured on a 4-point verbal rating scale is feasible. Evaluation of longer-term symptoms is difficult. TRIAL REGISTRATION NUMBER: ISRCTN: 85 710 690. EudraCT: 2016-003544-37.

Sensory feedback restoration in leg amputees improves walking speed, metabolic cost and phantom pain.

Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users that is associated with high mental and physical fatigue1-4. The lack of physiological feedback from the remaining extremity to the brain also contributes to the generation of phantom limb pain from the missing leg5,6. To determine whether neural sensory feedback restoration addresses these issues, we conducted a study with two transfemoral amputees, implanted with four intraneural stimulation electrodes7 in the remaining tibial nerve (ClinicalTrials.gov identifier NCT03350061). Participants were evaluated while using a neuroprosthetic device consisting of a prosthetic leg equipped with foot and knee sensors. These sensors drive neural stimulation, which elicits sensations of knee motion and the sole of the foot touching the ground. We found that walking speed and self-reported confidence increased while mental and physical fatigue decreased for both participants during neural sensory feedback compared to the no stimulation trials. Furthermore, participants exhibited reduced phantom limb pain with neural sensory feedback. The results from these proof-of-concept cases provide the rationale for larger population studies investigating the clinical utility of neuroprostheses that restore sensory feedback.