Targeted Muscle Reinnervation Patients Research Articles

Prophylactic Posterior Targeted Muscle Reinnervation (TMR) Approach in Below Knee (BKA) Amputation Settings

Background/Objective: Targeted muscle reinnervation (TMR) is a nerve reconstruction technique focused on improving phantom limb pain (PLP), residual limb pain (RLP), prosthesis function, and limiting neuroma formation. In below-knee-amputations (BKA), TMR performed "through-the-wound" is heavily documented. Alternatively, the "posterior approach" was developed to help increase visibility of peripheral nerves from the posterior fossa. This study focuses on the surgical efficiency and patient outcomes of the posterior approach compared to the through-the-wound approach. We hypothesize the posterior approach will be comparable toor improve time-to-prosthesis fitting, OR time, and pain scores.
 Methods: 157 patients underwent TMR at two hospitals in Indianapolis, IN, and were identified using CPT 64890. 39 patients underwent posterior approach TMR post-BKA. Data on demographics, follow-up/rehabilitation visits, post-operative complications, prosthesis fitting, and total OR time were collected. Additionally, 32 patients received TMR "through-the-wound", and total OR time, post-operative complications, and time-to-prosthesis fitting were tracked. Patient-reported outcome (PRO) surveys are being sent to patients pending IRB approval.
 Results: Of the 39 who received the posterior approach between 1/10/2020 and 4/6/2023, 25 received TMR in the right leg and 14 in the left. Following BKA, average time to TMR was 144 days. However, 18 patients received TMR directly after undergoing BKA (46.2%). Average OR time for acute and delayed posterior TMR patients was 208.06 minutes and 199.47 minutes, respectively. 10 patients reported post-operative complications (25.6%): dehiscence (12.8%) or infection (7.7%). 23 patients received prosthesis fitting on average 3 months post-op. Average OR time and time-to-prosthesis fitting for "through-the-wound" TMR surgeries were 192.84minutes and 5.81 months, respectively.
 Potential Impact: Posterior approach TMR had no significant impact on OR time, but time-to-prosthesis fitting significantly decreased. Once PRO surveys return, average long-term PLP and RLP can be determined. Preliminarily, posterior approach TMR improves aspects of patient outcomes while not compromising surgical efficiency.

Targeted Muscle Reinnervation at the Time of Amputation Decreases Recurrent Symptomatic Neuroma Formation.

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). 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. 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. 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. Therapeutic, III.

Targeted Muscle Reinnervation for Limb Amputation to Avoid Neuroma and Phantom Limb Pain in Patients Treated at a Pediatric Hospital.

Patients undergoing major limb amputation with TMR were included with minimum one year follow-up and completed questionnaires. Primary clinical outcomes included incidence of symptomatic neuromas, PLP, residual limb pain, narcotic use, and neuromodulator use. A follow-up phone survey was conducted assessing five pediatric Patient Reported Outcomes Measurement Information System (PROMIS) metrics adapted to assess residual limb and PLP. Nine patients (seven male and two female patients, avg. age = 16.83 ± 7.16 years) were eligible. Average time between surgery and phone follow-up was 21.3 ± 9.8 months. Average PROMIS Pediatric t-scores for measures of pain behavior, interference, quality-affective, and quality-sensory for both PLP and residual limb pain were nearly 1 standard deviation lower than the United States general pediatric population. One patient developed a symptomatic neuroma 1 year after surgery. Compared with an adult patient sample reported by Valerio et al, our TMR patients at Nationwide Children's Hospital (NCH) showed similar PLP PROMIS t-scores in pain behavior (50.1 versus 43.9) and pain interference (40.7 versus 45.6). Both pediatric and adult populations had similar residual limb pain including PROMIS pain behavior (36.7 adult versus 38.6 pediatric) and pain interference (40.7 adult versus 42.7 pediatric). TMR at the time of amputation is feasible, safe, and should be considered in the pediatric population.

Feasibility Study on Disentangling Muscle Movements in TMR Patients Through a Myokinetic Control Interface for the Control of Artificial Hands

Targeted muscle reinnervation (TMR) is a surgical procedure which allows to restore myoelectric control sources in people with proximal upper-limb amputations. However, the large physical displacement generally provoked by the reinnervated muscles following contraction can represent a drawback for the use of surface electrodes, which are affected by movement artifacts. In this regard, the viability of directly exploiting the physical displacement of muscles as control source would be beneficial. We recently introduced the so called <i>myokinetic interface</i>, aimed at transducing muscle movements into decipherable signals for artificial hands by tracking magnetic markers implanted inside the muscles. This work features the combination of the TMR procedure with such interface, in a non-invasive way. Two participants who underwent TMR surgery following above-the-elbow amputation were enrolled in this study. During two experimental sessions, we assessed the feasibility of: (i) disentangling muscle displacements associated with different degrees of freedom (DoFs) of the missing limb through video analysis, and (ii) discriminating different DoFs by tracking the displacement of five magnetic markers placed on the skin, over the reinnervated sites. A simple logistic regressor proved able to discriminate three different DoFs (six movements), with an average F1-score among classes and testing conditions of 0.84 (0.65) and 0.69 (0.60) for the video and the myokinetic data, for the first (second) participant, respectively. The presented outcomes encourage further investigations, and pave the way towards novel control strategies for artificial hands in TMR patients.

Control Strategies and Performance Assessment of Upper-Limb TMR Prostheses: A Review.

The evolution of technological and surgical techniques has made it possible to obtain an even more intuitive control of multiple joints using advanced prosthetic systems. Targeted Muscle Reinnervation (TMR) is considered to be an innovative and relevant surgical technique for improving the prosthetic control for people with different amputation levels of the limb. Indeed, TMR surgery makes it possible to obtain reinnervated areas that act as biological amplifiers of the motor control. On the technological side, a great deal of research has been conducted in order to evaluate various types of myoelectric prosthetic control strategies, whether direct control or pattern recognition-based control. In the literature, different control performance metrics, which have been evaluated on TMR subjects, have been introduced, but no accepted reference standard defines the better strategy for evaluating the prosthetic control. Indeed, the presence of several evaluation tests that are based on different metrics makes it difficult the definition of standard guidelines for comprehending the potentiality of the proposed control systems. Additionally, there is a lack of evidence about the comparison of different evaluation approaches or the presence of guidelines on the most suitable test to proceed for a TMR patients case study. Thus, this review aims at identifying these limitations by examining the several studies in the literature on TMR subjects, with different amputation levels, and proposing a standard method for evaluating the control performance metrics.

Targeted Muscle Reinnervation at the Time of Upper-Extremity Amputation for the Treatment of Pain Severity and Symptoms

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.

Targeted Muscle Reinnervation Reduces Pain and Improves Ambulation in Patients Undergoing Below-Knee Amputation: A Single-Institution Matched Cohort Study

Each year, 200,000 people will undergo a lower extremity amputation; 80% of those patients require an amputation because of critical ischemia or infection. After amputation, patients suffer from chronic pain, inability to ambulate, and high mortality rates. Targeted muscle reinnervation (TMR) is a nerve transfer procedure that redirects the surgically transected major sensory nerves into redundant motor nerves to prevent or to treat both neuroma and phantom limb pain. The purpose of this study was to evaluate the effect of TMR on pain and ambulation when it is performed at the time of below-knee amputation (BKA). This is a matched cohort study comparing 100 consecutive patients undergoing BKA with primary TMR and 100 consecutive patients undergoing BKA who were treated with traditional traction neurectomy. Patients’ charts were reviewed for the comorbidities in the Charlson Comorbidity Index. Postoperative clinic notes were reviewed for the presence of residual and phantom limb pain, severity of overall pain, and ambulatory status. Pharmacy records were reviewed for opioid and neuroleptic medication use. Obituary data were reviewed to determine mortality rates. There were 100 patients included in the TMR group, with an average age of 60 years and body mass index of 29 kg/m2; 84% had diabetes, 55% peripheral vascular disease, 43% end-stage renal disease on dialysis, 17% with a prior myocardial infarction, and 13% with a prior cerebrovascular accident. Average time to follow-up was 6.2 months for the TMR group and 18.7 months for the non-TMR group; 73% of TMR patients were pain free compared with 34% of non-TMR patients (P < .01). Average pain was 2.6 of 10 for the TMR group and 5.4 of 10 for the non-TMR group (P < .01); 14% of TMR patients endorsed residual limb pain compared with 59% of non-TMR patients (P < .01), and 18% of TMR patients endorsed phantom limb pain compared with 49% of non-TMR patients (P < .01). Compared with 26% of non-TMR patients, 6% of TMR patients were taking opioids (P < .01); 42% of TMR patients were taking neuroleptic medications compared with 50% of non-TMR patients (P = .15). Compared with 72% of non-TMR patients, 93% of TMR patients were ambulatory (P < .01). There was no significant difference in 12-month mortality rate (4.9% vs 6.0%; P = .80). When it is performed immediately at the time of BKA, TMR significantly reduces pain and improves ambulation in patients critically threatened by ischemia or infection. Optimizing pain and ambulation may be critical in improving further morbidity and mortality rates in this comorbid population of patients.

Preemptive Treatment of Phantom and Residual Limb Pain with Targeted Muscle Reinnervation at the Time of Major Limb Amputation

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 (TMR) at Time of Major Amputation Decreases Phantom and Residual Limb Pain

Background: A growing population of young soldiers returning from military conflict and civilians suffering from diabetes, peripheral vascular disease, and cancer contribute to the nearly two million people living with limb loss in the United States alone. A surprising majority of amputees suffer from chronic pain in the form of unpredictable neuroma-related residual limb and phantom limb pain. These conditions profoundly decrease patient function and quality of life, and despite a myriad of proposed therapies, there are no reliable treatment or prevention strategies for postamputation pain. Targeted muscle reinnervation (TMR) surgically transfers amputated nerves to redundant motor nerves to allow for physiologic nerve healing. In this study, TMR was proposed for prevention of postamputation pain. Methods: Immediate TMR was performed in 51 patients undergoing major limb amputation as a preemptive measure for symptomatic neuromas and phantom limb phenomena at two centers. Pain outcomes were assessed using an eleven-point Numerical Rating Scale (NRS) and the Patient-Reported Outcomes Measurement Information System (PROMIS), and were compared to a cross-section of 438 untreated amputee controls. Opioid prescription patterns were secondarily collected for TMR patients. Findings: Patients undergoing TMR concurrently at the time of major limb amputation had less phantom limb and residual limb pain compared to 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 (phantom) and 4 (residual) out of 10 in the general amputee population for phantom and residual limb pain (p=0.003 and p<0.001, respectively). Forty-five percent of TMR patients reported zero phantom limb pain, and 49.2% reported zero residual limb pain compared to approximately 20% for each in the general amputee cohort. Median PROMIS t-scores were lower in TMR patients than general amputee participants for both phantom limb pain: Pain Intensity (36.3 versus 48.3), Pain Behavior (50.1 versus 56.6), Pain Interference (40.7 versus 55.8) and residual limb pain: Pain Intensity (30.7 versus 46.8), Pain Behavior (36.7 versus 57.3), Pain Interference (40.7 versus 57.3). TMR was associated with 3.03 (phantom) and 3.92 (residual) times higher odds of decreasing pain severity compared to general amputee participants. Interpretation: Preemptive surgical handling of amputated nerves by targeted muscle reinnervation at the time of limb loss should be strongly considered for prevention of pathologic phantom limb pain and symptomatic neuroma-related pain. Funding Statement: This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Orthopaedic Research Program under Award No. W81XWH-13-2-0100. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. No authors were paid to write this article by a pharmaceutical company or other agency. The corresponding author, Ian L. Valerio, has full access to all the data in the study and had final responsibility for the decision to submit for publication. Declaration of Interests: None of the authors in this manuscript have any conflicts of interest. Ethics Approval Statement: This work was approved by The Ohio State University Institutional Review Board (Protocol Number 2017C0150). This work was approved by the Northwestern University Institutional Review Board (Protocol Number STU00205866).

Motor Unit Characteristics after Targeted Muscle Reinnervation.

Targeted muscle reinnervation (TMR) is a surgical procedure used to redirect nerves originally controlling muscles of the amputated limb into remaining muscles above the amputation, to treat phantom limb pain and facilitate prosthetic control. While this procedure effectively establishes robust prosthetic control, there is little knowledge on the behavior and characteristics of the reinnervated motor units. In this study we compared the m. pectoralis of five TMR patients to nine able-bodied controls with respect to motor unit action potential (MUAP) characteristics. We recorded and decomposed high-density surface EMG signals into individual spike trains of motor unit action potentials. In the TMR patients the MUAP surface area normalized to the electrode grid surface (0.25 ± 0.17 and 0.81 ± 0.46, p < 0.001) and the MUAP duration (10.92 ± 3.89 ms and 14.03 ± 3.91 ms, p < 0.01) were smaller for the TMR group than for the controls. The mean MUAP amplitude (0.19 ± 0.11 mV and 0.14 ± 0.06 mV, p = 0.07) was not significantly different between the two groups. Finally, we observed that MUAP surface representation in TMR generally overlapped, and the surface occupied by motor units corresponding to only one motor task was on average smaller than 12% of the electrode surface. These results suggest that smaller MUAP surface areas in TMR patients do not necessarily facilitate prosthetic control due to a high degree of overlap between these areas, and a neural information—based control could lead to improved performance. Based on the results we also infer that the size of the motor units after reinnervation is influenced by the size of the innervating motor neuron.

Noninvasive, Accurate Assessment of the Behavior of Representative Populations of Motor Units in Targeted Reinnervated Muscles

Targeted muscle reinnervation (TMR) redirects nerves that have lost their target, due to amputation, to remaining muscles in the region of the stump with the intent of establishing intuitive myosignals to control a complex prosthetic device. In order to directly recover the neural code underlying an attempted limb movement, in this paper, we present the decomposition of high-density surface electromyographic (EMG) signals detected from three TMR patients into the individual motor unit spike trains. The aim was to prove, for the first time, the feasibility of decoding the neural drive that would reach muscles of the missing limb in TMR patients, to show the accuracy of the decoding, and to demonstrate the representativeness of the pool of extracted motor units. Six to seven flexible EMG electrode grids of 64 electrodes each were mounted over the reinnervated muscles of each patient, resulting in up to 448 EMG signals. The subjects were asked to attempt elbow extension and flexion, hand open and close, wrist extension and flexion, wrist pronation and supination, of their missing limb. The EMG signals were decomposed using the Convolution Kernel Compensation technique and the decomposition accuracy was evaluated with a signal-based index of accuracy, called pulse-to-noise ratio (PNR). The results showed that the spike trains of 3 to 27 motor units could be identified for each task, with a sensitivity of the decomposition > 90%, as revealed by PNR. The motor unit discharge rates were within physiological values of normally innervated muscles. Moreover, the detected motor units showed a high degree of common drive so that the set of extracted units per task was representative of the behavior of the population of active units. The results open a path for a new generation of human-machine interfaces in which the control signals are extracted from noninvasive recordings and the obtained neural information is based directly on the spike trains of motor neurons.

Spatial Filtering Improves EMG Classification Accuracy Following Targeted Muscle Reinnervation

The combination of targeted muscle reinnervation (TMR) and pattern classification of electromyography (EMG) has shown great promise for multifunctional myoelectric prosthesis control. In this study, we hypothesized that surface EMG recordings with high spatial resolution over reinnervated muscles could capture focal muscle activity and improve the classification accuracy of identifying intended movements. To test this hypothesis, TMR subjects with transhumeral or shoulder disarticulation amputations were recruited. Spatial filters such as single differential filters, double differential filters, and various two-dimensional, high-order spatial filters were used, and the classification accuracies for fifteen different movements were calculated. Compared with monopolar recordings, spatially localized EMG signals produced increased accuracy in identifying the TMR patients' movement intents, especially for hand movements. When the number of EMG signals was constrained to 12, the double differential filters gave 5-15% higher classification accuracies than the filters with lower spatial resolution, but resulted in comparable accuracies to the filters with higher spatial resolution. These results suggest that double differential EMG recordings may further improve the TMR-based neural interface for robust, multifunctional control of artificial arms.

Targeted Muscle Reinnervation for Real-time Myoelectric Control of Multifunction Artificial Arms

Improving the function of prosthetic arms remains a challenge, because access to the neural-control information for the arm is lost during amputation. A surgical technique called targeted muscle reinnervation (TMR) transfers residual arm nerves to alternative muscle sites. After reinnervation, these target muscles produce electromyogram (EMG) signals on the surface of the skin that can be measured and used to control prosthetic arms. To assess the performance of patients with upper-limb amputation who had undergone TMR surgery, using a pattern-recognition algorithm to decode EMG signals and control prosthetic-arm motions. Study conducted between January 2007 and January 2008 at the Rehabilitation Institute of Chicago among 5 patients with shoulder-disarticulation or transhumeral amputations who underwent TMR surgery between February 2002 and October 2006 and 5 control participants without amputation. Surface EMG signals were recorded from all participants and decoded using a pattern-recognition algorithm. The decoding program controlled the movement of a virtual prosthetic arm. All participants were instructed to perform various arm movements, and their abilities to control the virtual prosthetic arm were measured. In addition, TMR patients used the same control system to operate advanced arm prosthesis prototypes. Performance metrics measured during virtual arm movements included motion selection time, motion completion time, and motion completion ("success") rate. The TMR patients were able to repeatedly perform 10 different elbow, wrist, and hand motions with the virtual prosthetic arm. For these patients, the mean motion selection and motion completion times for elbow and wrist movements were 0.22 seconds (SD, 0.06) and 1.29 seconds (SD, 0.15), respectively. These times were 0.06 seconds and 0.21 seconds longer than the mean times for control participants. For TMR patients, the mean motion selection and motion completion times for hand-grasp patterns were 0.38 seconds (SD, 0.12) and 1.54 seconds (SD, 0.27), respectively. These patients successfully completed a mean of 96.3% (SD, 3.8) of elbow and wrist movements and 86.9% (SD, 13.9) of hand movements within 5 seconds, compared with 100% (SD, 0) and 96.7% (SD, 4.7) completed by controls. Three of the patients were able to demonstrate the use of this control system in advanced prostheses, including motorized shoulders, elbows, wrists, and hands. These results suggest that reinnervated muscles can produce sufficient EMG information for real-time control of advanced artificial arms.