Low prevalence of painful neuroma and phantom limb pain in lower extremity amputations of leprosy patients

Aims This study aims to investigate phantom limb pain (PLP), PLP-related factors, and the effect of PLP on quality of life in patients who had undergone upper or lower extremity amputation. Methods One hundred four patients with unilateral amputation of the upper or lower extremity were included in this cross-sectional study. The patients were divided into two groups as patients with PLP and without PLP. Patients’ demographic (age, gender, marital status, education level, employment status) and clinical information (date of amputation, amputated limb, the side, level and cause of amputation, phantom limb sensation and pain, sleep disorder) and quality of life (Nottingham extended activities of daily living index) were compared between the groups. In addition, factors associated with PLP were analysed. Results Of the 104 patients, 47 patients (45.19%) had PLP. In the group with PLP, phantom sensation and sleep disturbance were significantly higher, whereas the time elapsed after amputation and Nottingham extended activities of daily living index score were significantly lower (p < 0.05). The relationship between PLP and sleep disorder and between PLP and marital status was significant (p < 0.05). Conclusions Our study results showed that PLP was associated with sleep disorder and marital status, and the quality of life was low in the group with PLP. Therefore, PLP evaluation should not be disregarded in amputees; PLP should be treated to increase quality of life.

This study describes the sensations and pain reported by persons with unilateral lower extremity amputations. Participants (n = 92) were recruited from two hospitals to complete the Prosthesis Evaluation Questionnaire which included questions about amputation related sensations and pain. Using a visual analog scale, participants reported the frequency, intensity, and bothersomeness of phantom limb, residual limb, and back pain and nonpainful phantom limb sensations. A survey of medication use for each category of sensations also was included. Statistical analyses revealed that nonpainful phantom limb sensations were common and more frequent than phantom limb pain. Residual limb pain and back pain were also common after amputation. Back pain surprisingly was rated as more bothersome than phantom limb pain or residual limb pain. Back pain was significantly more common in persons with above knee amputations. These results support the importance of looking at pain as a multidimensional rather than a unidimensional construct. They also suggest that back pain after lower extremity amputation may be an overlooked but very important pain problem warranting additional clinical attention and study.

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. Therapeutic, IV.

Lower extremity amputations are common, and postoperative neuropathic pain (phantom limb pain or symptomatic neuroma) is frequently reported. The use of active treatment of the nerve end has been shown to reduce pain but requires additional resources and should therefore be performed primarily in high-risk patients. The aim of this study was to identify the factors associated with the development of neuropathic pain following above-the-knee amputation, knee disarticulation, or below-the-knee amputation. Retrospectively, 1565 patients with an average follow-up of 4.3 years who underwent a primary above-the-knee amputation, knee disarticulation, or below-the-knee amputation were identified. Amputation levels for above-the-knee amputations and knee disarticulations were combined as proximal amputation level, with below-the-knee amputations being performed in 61 percent of patients. The primary outcome was neuropathic pain (i.e., phantom limb pain or symptomatic neuroma) based on medical chart review. Multivariable logistic regression was performed to identify independent factors associated with neuropathic pain. Postoperative neuropathic pain was present in 584 patients (37 percent), with phantom limb pain occurring in 34 percent of patients and symptomatic neuromas occurring in 3.8 percent of patients. Proximal amputation level, normal creatinine levels, and a history of psychiatric disease were associated with neuropathic pain. Diabetes, hypothyroidism, and older age were associated with lower odds of developing neuropathic pain. Neuropathic pain following lower extremity amputation is common. Factors influencing nerve regeneration, either increasing (proximal amputations and younger age) or decreasing (diabetes, hypothyroidism, and chronic kidney disease) it, play a role in the development of postamputation neuropathic pain. Risk, III.

Pre-operative sciatic nerve block vs postoperative surgeon-placed perineural stump catheter for prevention of phantom limb pain after below-knee amputation.

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.

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

Complex regional pain syndrome (CRPS) is a chronic, posttraumatic condition defined by severe pain and sensorimotor dysfunction. In cases of severe CRPS, patients request amputation, which may cause phantom limb pain (PLP) and residual limb pain (RLP). Targeted muscle reinnervation (TMR) reduces the risk of PLP and RLP. This report describes the use of TMR at the time of amputation in a series of patients with CRPS. Four patients (ages 38-71 years) underwent TMR at the time of amputation for CRPS between April 2018 and January 2019. Three patients had a history of trauma and surgery to the affected limb. All patients attempted pharmacologic and interventional treatments for 1-7 years before requesting amputation. Three patients underwent below-knee amputations (BKA) and one had an above-knee amputation (AKA). Target muscles included the soleus, gastrocnemius, and flexor hallucis longus (BKA), and semitendinosus, biceps femoris, and vastus medialis (AKA). Postoperative phantom and residual limb pain symptoms were collected via a telephone survey adapted from the Patient-Reported Outcomes Measurement Information System (PROMIS). There were no complications related to the TMR procedure. Average follow-up time was 12.75 months. Patients reported varied outcomes: two had RLP and PLP, one had RLP only, and one had PLP only. All patients reported successful prosthetic use. TMR may be performed at the time of amputation for CRPS. Further study is necessary to determine the effect of TMR on pain, pain medication use, prosthesis use, and other domains of function.

Many amputees are left with chronic localized pain, centralized pain, and phantom limb pain or sensation, often resulting from neuromas in the residual limb. Historically, there is no reliably effective intervention for pain associated with neuroma-related residual or phantom limb pain. Targeted muscle reinnervation (TMR) is a surgical procedure first described in 2002 that involves the transfer of residual nerves from amputated limbs to new muscle targets. TMR has been shown to significantly reduce neuroma pain and facilitate the use of prostheses. A prospective study was conducted of 61 patients who underwent TMR for neuroma treatment or prevention between 2017 and 2022. Primary outcomes included overall, phantom, and residual limb pain recorded using the Visual Analog Scale (VAS), as well as Patient-Reported Outcomes Measurement Information System (PROMIS) forms for Pain Intensity, Quality, Interference, and Behavior. Retrospective data was collected for a propensity-matched cohort of non-TMR amputees to compare pain outcomes. TMR was performed for 25 upper extremity and 35 lower extremity amputations, and 5 patients underwent TMR on multiple limbs. Significant reductions were observed in overall limb pain (-3.2 points), phantom limb pain (-2.6 points), and residual limb pain (-3.0 points) for the TMR cohort. Mean PROMIS scores for TMR patients were 49.7 for Pain Intensity, 54.0 for Pain Quality, 55.3 for Pain Interference, and 56.1 for Pain Behavior. At the 8.4-month follow-up, 43.8% of TMR patients (vs 84% of controls) remained on neuromodulators, opioids, or both, for pain control. TMR improved phantom and residual limb pain in amputees, as evidenced by clinically and statistically significant reductions in pain with reduced need for long-term opioids and/or neuromodulators. These findings support the current understanding of TMR but underscore the need for continued investigation to comprehensively assess the potential of this promising technique in improving the functional outcomes and quality of life in the amputee population.

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

Targeted Brain Rehabilitation: Development, Feasibility, and Usability of a Novel Virtual Reality System for Phantom Limb Pain Management and Amputee Rehabilitation.

Targeted muscle reinnervation (TMR) is a promising surgical modality for reducing post-amputation pain. We sought to provide a succinct overview of TMR specific to the lower extremity (LE) amputation population. A systematic review was performed per PRISMA guidelines. Ovid MEDLINE, PubMed, and Web of Science were queried for records using various combinations of Medical Subject Heading (MeSH) terms such as "LE "amputation," "below-knee amputation" (BKA), "above-knee amputation" (AKA), and "TMR." Primary outcomes included (1) operative techniques, (2) changes in neuroma, phantom limb pain (PLP), or residual limb pain (RLP), and (3) postoperative complications. Studies were only included if outcomes data were discretely provided for LE patients. Eleven articles examining 318 patients were identified. Average patient age was 47.5 ± 9.3 years, and most patients were male (n=246, 77.4%). Eight manuscripts (72.7%) described TMR at the index amputation. The average number of nerve transfers performed per TMR case was 2.1 ± 0.8, and the most commonly employed nerve was the tibial (178/498; 35.7%). Nine (81.8%) articles incorporated patient-reported outcomes after TMR, with common methods including the Numerical Rating Scale (NRS) and questionnaires. Four studies (33.3%) reported functional outcomes such as ambulation ability and prosthesis tolerance. Complications were described in seven manuscripts (58.3%), with postoperative neuroma development being the most common (21/371; 7.2%). The application of TMR to LE amputations is effective in reducing PLP and RLP with limited complications. Continued investigations are warranted to better understand patient outcomes specific to anatomic location using validated patient-reported outcome measures (PROM).

ABSTRACTBACKGROUND:High-energy casualties such as firearm injuries may result in extensive loss of soft tissue and bone in the lower extremities. Although the primary aim in these types of injuries is the preservation of the extremity, repeated surgical procedures for extremity salvage and subsequent restoration of function could have detrimental effects on the patient both physically and psychologically. The main aim of this study is to evaluate the physical and psychological outcomes of patients who underwent lower extremity amputation in the early period after a firearm injury compared with the results of patients who underwent amputation in the late period. We also evaluated the factors affecting the prognosis in patients undergoing late below-knee amputation (BKA).METHODS:This retrospective study included patients who underwent BKA following a lower extremity injury caused by firearms between March 2017 and March 2022. Patients who underwent emergency BKA at the first center they were taken to immediately after the injury constituted the early amputation (EA) group. Patients who were transferred to our tertiary-level referral center for continuation of treatment after the first intervention at another center and later underwent BKA constituted the late amputation (LA) group. The patients were evaluated regarding age, gender, amputation side, presence of phantom limb pain (PLP), and post-traumatic stress disorder (PTSD).RESULTS:Information was available from hospital records for a total of 35 patients; 16 in the EA group and 19 in the LA group. All patients were male. The mean age at the time of injury was 25.5±5.3 years (range, 20-45 years), and the mean follow-up period was 37±17 months (range, 25-72 months). In the comparison of PLP experienced, the difference between the groups was statistically significant, with PLP experienced by 1 (10%) patient in the EA group and by 9 (90%) in the LA group (p=0.010). PTSD was diagnosed in 3 (23%) patients in the EA group and 10 (77%) patients in the LA group (p=0.039).CONCLUSION:Patients who underwent late BKA were found to be affected by PLP and PTSD at a higher rate. When deciding on extremity-preserving surgery for patients with severe open injuries to the lower extremity, it is crucial to consider the poor outcomes associated with late BKA. Patients should be thoroughly informed about these negative outcomes.

This article is accompanied by the following Invited Commentary: Wittmann M, Matot I, Hoeft A. ESA Clinical Trials Network 2012. Eur J Anaesthesiol 2013; 30:208–210. The number of patients suffering from critical limb ischaemia is large and growing. For the population aged 60 to 90 years, the prevalence is estimated at 1% and increasing.1 Current literature suggests that about 25% of these patients will need to undergo amputation.2 Even with the increased use of interventional treatment of vascular disease, amputation remains a frequently performed procedure and for the United States alone, current projections estimate that the number of patients living with loss of a limb due to vascular disease will rise from the current number of 850 000 to 2 200 000 by the year 2050.3 The prevalence of phantom pain following surgical amputation is high. A recent study confined to patients undergoing lower limb amputation for peripheral vascular disease reported phantom limb pain in 79% of patients.4 Several studies have addressed the potential of analgesic interventions to reduce the incidence of chronic phantom pain. However, these have been hampered by small numbers of patients, and heterogeneous patient groups. A recent systematic review by Ypsilantis and Tang5 concluded that robust evidence to support a positive impact of anaesthetic interventions in the prevention of phantom limb pain is, to date, lacking. In a randomised controlled trial conducted by Karanikolas et al.,6 it was suggested that strict perioperative pain control using fixed regimens of nonopioid analgesics and patient-controlled opiate analgesia could reduce the incidence of phantom limb pain from 75 to 53%. Pilot studies investigating preventive effects of peripheral nerve blockade have shown conflicting results.7,8 Borghi et al.9 reported their experience in 71 patients treated with an elastomeric infusion system connected to a sciatic nerve catheter in place for a median duration of 1 month. Here, the incidence of phantom limb pain was 15%, and phantom limb sensations were present in 39% after 12 months. However, the incidence of severe phantom limb pain was only 3%. Therefore, peripheral nerve blockade may represent a safe and effective option to prevent phantom limb pain, but no adequately powered prospective randomised trial has investigated this possibility. Why certain patients develop ongoing pain postoperatively while in others, the pain resolves, is largely unknown and, to date, unpredictable, and is the reason for a genetic component of this study. Recent mono-zygotic versus dizygotic twin studies show that heritable components contribute up to two-thirds of the risk of developing chronic pain.10 Such data clearly suggest a genetic predisposition for the development of chronic pain. An additional aim of the present study is to advance identification of these genetic factors. This study is designed to compare two interventions thought to contribute to a decreased incidence of phantom limb pain (strict intravenous pain control versus strict intravenous pain control along with peripheral nerve block). There are two main research questions. First, under optimised intravenous perioperative analgesia, what is the incidence of chronic phantom limb pain 12 months after transtibial amputation for peripheral vascular disease? Second, what is the value of continuous sciatic nerve block added to optimised perioperative analgesia in patients undergoing transtibial amputation for peripheral vascular disease? The aim of the study is to test the hypothesis that a combination of optimised intravenous pain therapy and continuous sciatic nerve block decreases the prevalence of phantom limb pain 12 months after transtibial amputation for peripheral vascular disease when compared with optimised intravenous pain therapy alone. The study is interventional, prospective, randomised and double-blinded (blinding of patient and physician). Online computer-based randomisation, stratified according to planned anaesthetic technique (spinal/general anaesthesia), will be used. Previous outcome studies investigating the effect of optimised perioperative analgesia alone have indicated a prevalence of phantom limb pain 1 year after amputation of 45%.6 A meaningful clinical effect will be assumed when the prevalence of phantom limb pain 12 months after amputation can be reduced from 45 to 30%. Taking an alpha level of 0.05 and a power of 80%, the estimated sample size per group is 163 patients; assuming a drop-out rate of approximately 20%, the trial will recruit 163/0.8 = 200 patients per treatment group. The primary efficacy variable is the prevalence of chronic phantom limb pain at 12 months. This variable will be presented for both treatment groups as proportions together with 95% confidence intervals. Logistic regression analyses will be performed to assess the effect of potential influential variables such as single nucleotide polymorphisms, preamputation pain and surgical technique. The last observation carried forward procedure will be applied in case of withdrawals. For the intention-to-treat analysis, the incidence of phantom limb pain at 7 days, 1 and 6 months will be carried forward to 1 year in case the (1-year) observation is missing. The aim is to recruit a total of 10 to 15 centres through the European Society of Anaesthesiology Clinical Trial Network. We aim to generate a network of hospitals performing approximately 400 transtibial amputations for peripheral vascular disease per year. Assuming a 50% inclusion rate and a desired inclusion of 400 patients, the recruitment period is predicted to last between 2 and 2.5 years, followed by 1-year follow-up. Thus, including follow-up, the study is projected to last for an estimated 3.5 years. Patients undergoing elective transtibial amputation for peripheral vascular disease, aged more than 18 years and with the American Society of Anesthesiologists' (ASA) status II to IV, will be included. We will exclude patients with a contraindication to peripheral regional anaesthesia, allergy to local anaesthetics, prior amputation resulting in current phantom limb pain, severe psychiatric disease, pregnancy or breastfeeding amputation for tumour surgery, traumatic amputation and inability of the patient to give written and informed consent. All patients will receive 'optimised intravenous pain control'. The key components of this regimen are the administration of low-dose ketamine, patient-controlled analgesia using strong opioids, and the use of nonopioids (for example paracetamol and/or metamizol). A sciatic nerve catheter will be inserted using ultrasound guidance preoperatively in all patients. Patients will receive general or spinal anaesthesia at the discretion of the treating physician. Global anaesthesia parameters will be recorded. Surgical methods are at the discretion of the treating surgeon, but will be recorded. The only interventions and standardisations will be those performed in relation to perioperative pain therapy. According to their randomisation, patients will follow one of the two standardised pain therapy regimens until 1 week postoperatively: optimised intravenous treatment ('Control', n = 200) with administration of isotonic saline via the sciatic nerve catheter; or optimised intravenous treatment along with sciatic nerve block ('Intervention', n = 200) with administration of a local anaesthetic via the sciatic nerve catheter. For all patients, participation in this study results in a thorough and continuous evaluation and strict treatment of perioperative pain. For ethical reasons, a true 'conventional' pain control group as described in previous trials (opioids administered intramuscularly or subcutaneously as needed, no strict control of pain scores and therapy) will not be included in the present study because these groups have featured excessive pain scores and a very high probability of chronic phantom limb pain.6,11 Data entries will be made on a paper version of the case report form. These will then be transferred to an electronic case report form (eCRF) in the OpenClinica software (Waltham, Massachusetts, USA). All investigators will 'log-in' with a personal code. All changes or additions to the data are tracked by the data management system in the audit trail. Access to the data entry system and eCRF is managed by the European Society of Anaesthesiology Research Office and protected by a personalised user name and password. The primary outcome measure is the prevalence of phantom limb pain 12 months postoperatively defined (yes/no) as follows: pain in the amputated area of the limb with a corresponding numerical rating scale score of at least 2 during the preceding 4 weeks (constant or at least three episodes) or ingestion of drugs administered specifically to treat phantom limb pain (classified as none, nonopioid, weak opioid, strong opioid, antidepressant, anticonvulsant, other). Selected secondary outcome measures include the incidence of phantom limb pain at 7 days, 1 and 6 months; McGill Pain Questionnaire (short-form MPQ) preoperatively and postoperatively at day 7, and 1, 6 and 12 months postoperatively; SF-12 quality of life score; overall benefit of analgesia score (OBAS) during the first postoperative week; recording of surgical handling of nerves and surgical technique; and genotype of patients assessed preoperatively. Gene haplotype will be assayed for association with acute to chronic pain conversion using single nucleotide polymorphisms from known risk factor genes including GCH1, KCNS1, Nav1.7 and P2X7R.12 This study will be conducted by the Academic Medical Center, University of Amsterdam (sponsor) and will be supported by the Clinical Trial Network, European Society of Anaesthesiology. The aim is to make a scientific case for or against the routine use of perioperative peripheral nerve blockade to prevent phantom limb pain after transtibial amputations. Acknowledgements Assistance with the article: none declared. Financial support and sponsorship: the study is funded by the European Society of Anaesthesiology (ESA). Submitted on behalf of the members of the Steering Committee: D.A. Legemate (Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands), F. Nollet (Department of Rehabilitation Medicine, Academic Medical Center, University of Amsterdam, The Netherlands), H. Ulmer (Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Austria) and J.P. Rathmell (Center for Pain Medicine, Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA). Conflicts of interest: none declared. Comment from the Editor: this article was checked by the editors but was not sent for external peer review.

Introduction Targeted Muscle Reinnervation (TMR) is an innovative surgical procedure initially designed for upper-limb amputations, which has shown growing potential for improving functional outcomes in below-knee amputees. TMR involves redirecting severed nerves from the amputated limb to nearby residual muscles, allowing these muscles to act as amplifiers for nerve signals, thereby improving prosthetic control. Recent advancements in TMR for below-knee amputations have highlighted its ability to reduce post-amputation complications, such as neuroma pain and phantom limb pain, while offering enhanced control over prosthetic limbs, thus improving mobility and quality of life. Methods Following PRISMA guidelines, a systematic review was conducted, sourcing studies up to May 2024 from PubMed, Cochrane Library, Scopus, Springer, and Epistemonikos. The analysis included randomized controlled trials (RCTs) and clinical trials. A meta-analysis was performed to assess phantom limb pain reduction, while study quality was evaluated using RoB 2.0, ROBINS-I, and ROBINS-E. Meta-regression examined the influence of variables such as age and sex on pain outcomes. Results Seven studies, including 363 patients, were analyzed. The meta-analysis showed that TMR significantly reduced phantom limb pain (MD: -1.74; 95% CI: -2.46 to -1.02; P&lt;0.00001; I2=0%). However, the pooled risk ratio for phantom pain incidence (RR: 1.58; 95% CI: 0.61 to 4.11; P=0.35; I2=93%) indicated variable outcomes. Conclusion TMR significantly reduces phantom limb pain and improves prosthetic control, particularly for patients with SCC of the foot, ultimately enhancing their quality of life.