Approximately 25 percent of major limb amputees will develop chronic localized symptomatic neuromas and phantom limb pain in the residual limb. A method to treat and possibly prevent these pain ...symptoms is targeted reinnervation. Previous studies prove that targeted reinnervation successfully treats and, in some cases, resolves peripheral neuropathy and phantom limb pain in patients who have undergone previous amputation (i.e., secondary targeted reinnervation). This article seeks to share the authors’ clinical indications and surgical technique for targeted muscle reinnervation in below-knee amputation, a surgical description currently absent from our literature. Targeted reinnervation for the below-knee amputee has been performed on 22 patients at the authors’ institution. Each patient has been followed on an outpatient basis for 1 year to evaluate symptoms of neuroma or phantom limb pain, patient satisfaction, and functionality. All subjects have denied neuroma pain following amputation. The majority of subjects reported phantom pain at 1 month. However, at 3 months, all patients reported resolution of this pain. Dumanian et al. first noted the improvement of symptomatic neuroma and phantom limb pain in patients undergoing targeted reinnervation to provide intuitive control of upper limb prostheses. These findings have been substantiated by multiple previous studies at various amputation levels. This study extends the success of targeted muscle reinnervation to below-knee amputations and provides a description for this technique.
OBJECTIVE:To compare targeted muscle reinnervation (TMR) to “standard treatment” of neuroma excision and burying into muscle for postamputation pain.
SUMMARY BACKGROUND DATA:To date, no intervention ...is consistently effective for neuroma-related residual limb or phantom limb pain (PLP). TMR is a nerve transfer procedure developed for prosthesis control, incidentally found to improve postamputation pain.
METHODS:A prospective, randomized clinical trial was conducted. 28 amputees with chronic pain were assigned to standard treatment or TMR. Primary outcome was change between pre- and postoperative numerical rating scale (NRS, 0–10) pain scores for residual limb pain and PLP at 1 year. Secondary outcomes included NRS for all patients at final follow-up, PROMIS pain scales, neuroma size, and patient function.
RESULTS:In intention-to-treat analysis, changes in PLP scores at 1 year were 3.2 versus −0.2 (difference 3.4, adjusted confidence interval (aCI) −0.1 to 6.9, adjusted P = 0.06) for TMR and standard treatment, respectively. Changes in residual limb pain scores were 2.9 versus 0.9 (difference 1.9, aCI −0.5 to 4.4, P = 0.15). In longitudinal mixed model analysis, difference in change scores for PLP was significantly greater in the TMR group compared with standard treatment mean (aCI) = 3.5 (0.6, 6.3), P = 0.03. Reduction in residual limb pain was favorable for TMR (P = 0.10). At longest follow-up, including 3 crossover patients, results favored TMR over standard treatment.
CONCLUSIONS:In this first surgical RCT for the treatment of postamputation pain in major limb amputees, TMR improved PLP and trended toward improved residual limb pain compared with conventional neurectomy.
TRIAL REGISTRATION:NCT 02205385 at ClinicalTrials.gov.
A majority of the nearly 2 million Americans living with limb loss suffer from chronic pain in the form of neuroma-related residual limb and phantom limb pain (PLP). Targeted muscle reinnervation ...(TMR) surgically transfers amputated nerves to nearby motor nerves for prevention of neuroma. The objective of this study was to determine whether TMR at the time of major limb amputation decreases the incidence and severity of PLP and residual limb pain.
A multi-institutional cohort study was conducted between 2012 and 2018. Fifty-one patients undergoing major limb amputation with immediate TMR were compared with 438 unselected major limb amputees. Primary outcomes included an 11-point Numerical Rating Scale (NRS) and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behavior, and interference.
Patients who underwent TMR had less PLP and residual limb pain compared with untreated amputee controls, across all subgroups and by all measures. Median “worst pain in the past 24 hours” for the TMR cohort was 1 out of 10 compared to 5 (PLP) and 4 (residual) out of 10 in the control population (p = 0.003 and p < 0.001, respectively). Median PROMIS t-scores were lower in TMR patients for both PLP (pain intensity 36.3 vs 48.3, pain behavior 50.1 vs 56.6, and pain interference 40.7 vs 55.8) and residual limb pain (pain intensity 30.7 vs 46.8, pain behavior 36.7 vs 57.3, and pain interference 40.7 vs 57.3). Targeted muscle reinnervation was associated with 3.03 (PLP) and 3.92 (residual) times higher odds of decreasing pain severity compared with general amputee participants.
Preemptive surgical intervention of amputated nerves with TMR at the time of limb loss should be strongly considered to reduce pathologic phantom limb pain and symptomatic neuroma-related residual limb pain.
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.
Targeted muscle reinnervation (TMR) is a technique for the management of peripheral nerves in amputation. Phantom limb pain (PLP) and residual limb pain (RLP) trouble many patients after amputation, ...and TMR has been shown to reduce this pain when performed after the initial amputation. We hypothesize that TMR at the time of amputation may improve pain for patients after major upper-extremity amputation.
We conducted a retrospective review of patients who underwent major upper-extremity amputation with TMR performed at the time of the index amputation (early TMR). Phantom limb pain and RLP intensity and associated symptoms were assessed using the numeric rating scale (NRS), the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Intensity Short-Form 3a, the Pain Behavior Short-Form 7a, and the Pain Interference Short-Form 8a. The TMR cohort was compared with benchmarked data from a sample of upper-extremity amputees.
Sixteen patients underwent early TMR and were compared with 55 benchmark patients. More than half of early TMR patients were without PLP (62%) compared with 24% of controls. Furthermore, half of all patients were free of RLP compared with 36% of controls. The median PROMIS PLP intensity score for the general sample was 47 versus 38 in the early TMR sample. Patients who underwent early TMR reported reduced pain behaviors and interference specific to PLP (50 vs 53 and 41 vs 50, respectively). The PROMIS RLP intensity score was lower in patients with early TMR (36 vs 47).
This study demonstrates that early TMR is a promising strategy for treating pain and improving the quality of life in the upper-extremity amputee. Early TMR may preclude the need for additional surgery and represents an important technique for peripheral nerve surgery.
Therapeutic IV.
Painful neuroma formation is a common and debilitating sequela of traumatic or oncologic nerve amputations. Studies suggest that isolating transected nerve stumps within protective caps during ...amputation surgery or revision procedures may assist in preventing symptomatic nerve-end neuroma formation. This study evaluated the local effects of two porcine small intestine submucosa (pSIS) nerve caps of differing configurations on a terminal nerve end in an animal model. The tibial nerves of 57 Sprague Dawley rats were transected and transposed to the lateral hind leg. The nerves were treated with one of three SIS materials, including (i) a nerve cap with spiraling chambering, termed spiral nerve cap (SNC), (ii) a nerve cap with bifurcated chambers termed chambered nerve cap (CNC), or (iii) an open tube. The surgical control consisted of nerve stumps that were not treated. Overall tissue response, axonal swirling, optical density of axons, and behavioral pain response were quantified at 8 and 12 weeks postoperatively. There were no notable differences between the performance of the SNC and CNC groups. The pSIS nerve caps mitigated aberrant axonal regeneration and decreased neuroma formation and associated pain response. These findings suggest that nerve caps with internal chambers for axonal outgrowth may improve axonal alignment, therefore reducing the likelihood of symptomatic neuroma formation.
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.
(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)?
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.
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).
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 IV, therapeutic study.
Background
We describe a multidisciplinary approach for comprehensive care of amputees with concurrent targeted muscle reinnervation (TMR) at the time of amputation.
Methods
Our TMR cohort was ...compared to a cross‐sectional sample of unselected oncologic amputees not treated at our institution (N = 58). Patient‐Reported Outcomes Measurement Information System (NRS, PROMIS) were used to assess postamputation pain.
Results
Thirty‐one patients underwent amputation with concurrent TMR during the study; 27 patients completed pain surveys; 15 had greater than 1 year follow‐up (mean follow‐up 14.7 months). Neuroma symptoms occurred significantly less frequently and with less intensity among the TMR cohort. Mean differences for PROMIS pain intensity, behavior, and interference for phantom limb pain (PLP) were 5.855 (95%CI 1.159‐10.55; P = .015), 5.896 (95%CI 0.492‐11.30; P = .033), and 7.435 (95%CI 1.797‐13.07; P = .011) respectively, with lower scores for TMR cohort. For residual limb pain, PROMIS pain intensity, behavior, and interference mean differences were 5.477 (95%CI 0.528‐10.42; P = .031), 6.195 (95%CI 0.705‐11.69; P = .028), and 6.816 (95%CI 1.438‐12.2; P = .014), respectively. Fifty‐six percent took opioids before amputation compared to 22% at 1 year postoperatively.
Conclusions
Multidisciplinary care of amputees including concurrent amputation and TMR, multimodal postoperative pain management, amputee‐centered rehabilitation, and peer support demonstrates reduced incidence and severity of neuroma and PLP.
Active treatment (targeted muscle reinnervation TMR or regenerative peripheral nerve interfaces RPNIs) of the amputated nerve ends has gained momentum to mitigate neuropathic pain following ...amputation. Therefore, the aim of this study is to determine the predictors for the development of neuropathic pain after major upper extremity amputation.
Retrospectively, 142 adult patients who underwent 148 amputations of the upper extremity between 2000 and 2019 were identified through medical chart review. All upper extremity amputations proximal to the metacarpophalangeal joints were included. Patients with a follow-up of less than 6 months and those who underwent TMR or RPNI at the time of amputation were excluded. Neuropathic pain was defined as phantom limb pain or a symptomatic neuroma reported in the medical charts at 6 months postoperatively. Most common indications for amputation were oncology (
= 53, 37%) and trauma (
= 45, 32%), with transhumeral amputations (
= 44, 30%) and shoulder amputations (
= 37, 25%) being the most prevalent.
Neuropathic pain occurred in 42% of patients, of which 48 (32%) had phantom limb pain, 8 (5.4%) had a symptomatic neuroma, and 6 (4.1%) had a combination of both. In multivariable analysis, traumatic amputations (odds ratio OR: 4.1,
= 0.015), transhumeral amputations (OR: 3.9,
= 0.024), and forequarter amputations (OR: 8.4,
= 0.003) were independently associated with the development of neuropathic pain.
In patients with an upper extremity amputation proximal to the elbow or for trauma, there is an increased risk of developing neuropathic pain. In these patients, primary TMR/RPNI should be considered and this warrants a multidisciplinary approach involving general trauma surgeons, orthopaedic surgeons, plastic surgeons, and vascular surgeons.
Bone tissue engineering (BTE) intends to restore structural support for movement and mineral homeostasis, and assist in hematopoiesis and the protective functions of bone in traumatic, degenerative, ...cancer, or congenital malformation. While much effort has been put into BTE, very little of this research has been translated to the clinic. In this review, we discuss current regenerative medicine and restorative strategies that utilize tissue engineering approaches to address bone defects within a clinical setting. These approaches involve the primary components of tissue engineering: cells, growth factors and biomaterials discussed briefly in light of their clinical relevance. This review also presents upcoming advanced approaches for BTE applications and suggests a probable workpath for translation from the laboratory to the clinic.
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