Muscle Reinnervation Research Articles

Early and Late Intrinsic Hand Muscle Reinnervation After End-to-Side AIN to Ulnar Motor Nerve Transfer.

The "supercharge" end-to-side (SETS) anterior-interosseous-nerve (AIN) to ulnar-motor nerve transfer is used to improve intrinsic muscle recovery in cases of severe ulnar nerve compression or proximal axonotmetic injuries. Previous work has found differing intrinsic muscle recovery after this transfer. The objectives of this study were to examine the patterns of recovery in first dorsal interossei (FDI) and abductor digiti minimi (ADM) and the impact of AIN transfer to a specific fascicular location on the ulnar-motor nerve. A retrospective review of one fellowship-trained surgeon's consecutive patients at a single center from December 2019 to September 2021 was conducted. Patients who had an AIN to ulnar-motor nerve transfer for any indication were included and were excluded if they had less than 9 months follow-up. Seventeen patients were included (88% male, mean age 55 ± 14 years). At early follow-up, compound muscle action potential amplitudes for ADM and FDI did not increase. Compound muscle action potential amplitude for ADM significantly increased at late follow-up (P < .01). Average British Medical Research Council (BMRC) strength increased at early follow-up for FDI (P < .05), but not ADM. The proportion of patients with BMRC ≥ 3 increased for FDI (P < .01) and ADM (P < .05) at late follow-up. Volar-ulnar AIN insertion position did not have a clear effect on outcomes. The SETS AIN to ulnar-motor nerve transfer demonstrates clinical and electrophysiologic evidence of intrinsic muscle recovery and reinnervation, with differing recovery of outcomes. The role of specific fascicular targeting is still unclear and required further examination as does the mechanism behind differing intrinsic recovering.

Surgical Treatments for Facial Aberrant Reinnervation Syndrome: A Systematic Review.

Background: Facial aberrant reinnervation syndrome is characterized by aberrant facial muscle reinnervation after facial nerve injury producing facial synkinesis, hypertonicity, and muscle spasm. Objective: To systematically review the surgical treatments for facial aberrant reinnervation syndrome and assess their effectiveness as measured by patient-reported outcomes, physician-graded outcomes, or computer-automated grading systems. Methods: We conducted a systematic review using PubMed, Embase, and Cochrane CENTRAL in accordance with PRISMA guidelines. Texts reporting outcomes of any surgical treatment for facial aberrant reinnervation syndrome from 2003 to 2023 were included. Results: After screening, 25 studies with 731 patients were included. Surgical procedures included selective neurectomy (SN), selective myectomy (SM), cross-facial nerve graft, masseter nerve transfer, and gracilis muscle transfer. All surgical techniques and combinations showed significant improvement in at least one clinical outcome measure from baseline (p < 0.05), although one study found no significant improvement. Thirty different outcome measures were used, the most common being the FaCE and eFACE scales (seven studies each). Conclusions: All surgical procedures in this review yield improved clinical outcome measures for facial aberrant reinnervation syndrome, with SN and SM being the dominant surgical treatments. Standardized outcome assessment and more nuanced patient evaluation are necessary to determine the most effective surgical treatments.

A nanofibrous polycaprolactone/collagen neural guidance channel filled with sciatic allogeneic schwann cells and platelet-rich plasma for sciatic nerve repair.

Sciatic nerve damage, a common condition affecting approximately 2.8% of the US population, can lead to significant disability due to impaired nerve signal transmission, resulting in loss of sensation and motor function in the lower extremities. In this study, a neural guidance channel was developed by rolling a nanofibrous scaffold produced via electrospinning. The scaffold's microstructure, biocompatibility, biodegradation rate, porosity, mechanical properties, and hemocompatibility were evaluated. Platelet-rich plasma (PRP) activated with 30,000 allogeneic Schwann cells (SCs) was injected into the lumen of the channels following implantation into a rat model of sciatic nerve injury. Recovery of motor function, sensory function, and muscle re-innervation was assessed using the sciatic function index (SFI), hot plate latency time, and gastrocnemius muscle wet weight loss. Results showed mean hot plate latency times of Autograft: 7.03, PCL/collagen scaffolds loaded with PRP and SCs (PCLCOLPRPSCs): 8.34, polymer-only scaffolds (PCLCOL): 10.66, and untreated animals (Negative Control): 12.00. The mean SFI values at week eight were Autograft: -49.30, PCLCOLPRPSCs: -64.29, PCLCOL: -75.62, and Negative Control: -77.14. The PCLCOLPRPSCs group showed a more negative SFI compared to the Autograft group but performed better than both the PCLCOL and Negative Control groups. These findings suggest that the developed strategy enhanced sensory and functional recovery compared to the negative control and polymer-only scaffold groups.

Pain Remission Following Delayed Targeted Muscle Reinnervation in Amputees.

Targeted muscle reinnervation (TMR) has demonstrated efficacy for treatment of neuropathic pain. This study aims to identify patients for whom delayed TMR may be most effective and to identify associated factors for favorable pain outcomes in this patient population. An analysis was conducted on prospectively enrolled amputee patients who underwent delayed TMR at a tertiary care center from 2017 to 2024. Data on demographics, comorbidities, surgical details, and pain outcomes were collected. Patient reported pain severity on a 0-10 scale was prospectively collected. The main pain outcome was pain remission (achieving the minimally clinically important difference (MCID)). Additionally, sustained mild pain (pain score ≤ 3/10 for ≥ 3 months), and pain disappearance (pain score 0/10 for ≥ 3 months) were assessed. Multivariable regression analyses identified factors influencing pain outcomes. Out of 101 patients included in this study, 64 patients (63.4%) achieved pain remission within a two-year post-operative period, and 37 patients (36.6%) did not. Sustained mild pain, which could be achieved in addition to pain remission, was achieved by 45.8% of patients, with 17.8% of these achieving complete pain disappearance. Patients achieving pain remission demonstrated lower pain over the entire post-operative trajectory (p < 0.001). Lower pre-operative pain scores, absence of depression, no pre-operative opioid use, lower Elixhauser Comorbidity Index, and distal amputation levels were correlated with favorable outcomes following delayed TMR (p < 0.05). Pre-operative pain severity, psychiatric comorbidities, and opioid use significantly influenced pain outcomes, emphasizing the need for comprehensive patient assessment. These findings will help with patient stratification and pre-operative counseling to support patients who are best suitable for delayed TMR surgery.

How timing and preexisting pain affect outcomes of TMR: a systematic review

Introduction: Targeted muscle reinnervation (TMR) is increasingly common in the care of major limb amputation to limit amputation-related pain. This review aims to elucidate how chronic pain states and length of delay prior to TMR affect its success and outcomes. Methods: Manuscripts were collected from three databases. Articles were first screened and excluded based on exclusion criteria. The remaining manuscripts were independently reviewed to determine inclusion. Article and patient demographics, as well as pain outcomes, were extracted. Data were analyzed based on pain condition, amputation vs. neuroma, and time from amputation/injury to surgery. Results: The literature search yielded 723 articles, with 41 meeting the inclusion criteria. Twenty-one articles included patients with residual limb pain (RLP) and phantom limb pain (PLP), including 14 on amputation and 6 on neuroma excision. Five articles included cancer-related amputation. Complex Regional Pain Syndrome (CRPS) was discussed in 3 articles, ischemia or infection in 2 articles, and neurofibromatosis 1 in 1 article. Twenty-two articles described TMR at the time of amputation. Conclusions: TMR is effective at preventing neuroma formation and limiting pain when performed at the time of amputation. Delayed patients had a greater improvement in RLP but less of an improvement in PLP, when assessed against immediate TMR patients who were compared to non-TMR standard amputees. In the presence of chronic pain states, such as CRPS, there is also improved analgesia. However, current clinical data are limited, indicating a need for further research into the use of TMR for chronic pain management.

Robotic microsurgery for pediatric peripheral nerve surgery

The technology of microsurgical robotic systems has shown potential benefit during the last decade for a variety of microsurgical procedures, such as vascular anastomoses, lymphatic anastomoses or nerve coaptation. At the same time, peripheral nerve surgery has produced ever more sophisticated nerve transfers in which the smallest nerve structures are connected to each other. Following obstetric brachial plexus injuries, nerve reconstruction surgery is often required in the first few years of life in order to improve the function of the affected arm, including nerve transfers to denervated muscles, which enable reinnervation of target muscles. In pediatric patients, these donor-nerve structures are even smaller than in adults, which further increases the demands to the microsurgeon. In this publication, we show the possible applications, capabilities and limitations of a dedicated microsurgical robotic system for nerve transfers in pediatric patients.

Surgical Complications after Targeted Muscle Reinnervation at a Safety-Net Hospital.

Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) can reduce neuroma formation and phantom limb pain (PLP) after lower extremity (LE) amputation. These techniques have not been studied in safety-net hospitals. This study aims to examine the surgical complication rates after TMR and/or RPNI at an academic safety-net hospital in an urban setting. This was a retrospective review of patients older than 18 years who had prior above-knee guillotine amputation (AKA) or below-knee guillotine amputation (BKA) and underwent stump formalization with TMR and/or RPNI from 2020 to 2022. Demographics, medical history, and operative and postoperative characteristics were collected. The primary outcome was any surgical complication, defined as infection, dehiscence, hematoma, neuroma, or reoperation. Univariate analysis was conducted to identify variables associated with surgical complications and PLP. Thirty-two patients met the inclusion criteria. The median age was 52 years, and 75% were males. Indications for amputation included diabetic foot infection (71.9%), necrotizing soft tissue infection (25.0%), and malignancy (3.1%). BKA was the most common indication for formalization (93.8%). Most patients (56.3%) had formalization with TMR and RPNI, 34.4% patients had TMR only, and 9.4% had RPNI alone. The incidence of postoperative complications was 46.9%, with infection being the most common (31.3%). The median follow-up time was 107.5 days. There was no significant difference in demographics, medical history, or operative characteristics between patients who did and did not have surgical complications. However, there was a trend toward higher rates of PLP in patients who had a postoperative wound infection (p = 0.06). Overall complication rates after LE formalization with TMR and/or RPNI at our academic safety-net hospital were consistent with reported literature. Given the benefits, including reduced chronic pain and lower health care costs, we advocate for the wider adoption of these techniques at other safety-net hospitals.

Targeted Muscle Reinnervation Compared to Standard Peripheral Nerve Management Following Amputation: A Systematic Review and Meta-Analysis.

Chronic pain remains a significant challenge for individuals following limb amputation, with incidence of painful neuromas, phantom limb pain (PLP), and residual limb pain (RLP). Targeted muscle reinnervation (TMR) is a surgical technique designed to restore motor control information lost during amputation by redirecting residual nerves to new muscle targets. This systematic review and meta-analysis aims to compare patient-reported and functional outcomes following amputation with either TMR or standard neurological treatment (SNT). The study also includes an examination of primary versus secondary TMR and explores outcomes in highly comorbid patient populations. A search of central databases was performed, and meta-analysis was completed on extracted data where possible. Eleven studies were identified. Results indicate a significant reduction in PLP and RLP in patients undergoing TMR compared to SNT using various pain scores. TMR also demonstrates improved functional outcomes and decreased opioid use. Furthermore, results indicated patients who underwent TMR at the time of amputation (primary TMR) had improved pain scores compared with those who had TMR performed later (secondary TMR). The review emphasizes the benefits of TMR as a valuable surgical adjunct for amputee patients, while also highlighting the need for further research, especially in comorbid populations.

Outcome of End to Side Nerve Modified Double Oberlin Procedure and End to End Dorsal Approach Spinal Accessory to Suprascapular Nerve in Partial Postganglionic BPI: A Case Report

Introduction: Brachial plexus injury (BPI) is a devastating peripheral nerve injury that mostly affecting young men, often due to motor vehicle accidents. BPIs can be classified into preganglionic and postganglionic lesions, with postganglionic injuries allowing potential nerve regeneration. The Oberlin method, aimed at reinnervating the biceps, and the Mackinnon technique, targeting both biceps and brachialis muscles, have shown promising outcomes in BPI management. Case report: A 45-year-old man presented with right hand weakness and occasional tingling in the upper arm and fingers two months after a motorcycle accident. Motor examination revealed muscle strength of 0/5 in the right trapezius, rhomboids, serratus anterior (positive winging scapula), pectoralis minor and major, latissimus dorsi, deltoid, biceps, and elbow flexion. Wrist and finger functions remained intact. Diagnosed with post-ganglionic BPI, the patient underwent two nerve transfer surgeries: the Mackinnon technique, transferring the spinal accessory nerve to the suprascapular nerve to reinnervate shoulder muscles, and the Double Oberlin procedure, transferring fascicles from the median and ulnar nerves to the musculocutaneous nerve for reinnervation of the biceps and brachialis muscles. Post-surgery, the patient engaged in an aggressive rehabilitation program focusing on strength, range of motion, and sensory re-education. Over nine months, the patient showed significant improvement in elbow flexion (MRC grade 3), wrist extension (MRC grade 5), hand grip strength (MRC grade 3) with improved sensation across the affected limb. He returned to work and daily activities with mild residual weakness and sensory deficits. Discussion: This case illustrates the effectiveness of the Mackinnon and Double Oberlin nerve transfer techniques in restoring function in a patient with total post-ganglionic BPI. The Mackinnon technique enabled shoulder muscle reinnervation, essential for abduction and stabilization, while the Double Oberlin procedure enhanced elbow flexion by reinnervating both the biceps and brachialis muscles. The combined surgical and intensive rehabilitation approach facilitated significant functional recovery. Conclusion: The successful application of the Double Oberlin and Mackinnon techniques in this case demonstrates their potential in managing total post-ganglionic BPI. Early surgical intervention and consistent rehabilitation are crucial for optimizing recovery outcomes. This case highlights the importance of a multidisciplinary approach in treating complex peripheral nerve injuries. Keywords: Double Oberlin, Mackinnon, Brachial Plexus Injury

The Use of Grayscale Muscle Ultrasound to Indicate Muscle Recovery After Peripheral Nerve Reconstruction.

This study aimed to validate the use of grayscale muscle ultrasound by measuring echo intensity to longitudinally evaluate functional muscle reinnervation in a rabbit peroneal nerve defect model. Eighteen New Zealand White rabbits underwent a 30-mm peroneal nerve reconstruction with autografts or decellularized allografts. Ultrasound measurements of tibialis anterior muscles were performed before surgery and at 4, 8, 12, 16, 20, and 24 weeks postoperatively and included cross-sectional muscle area, mean gray value (MGV), and mean gray value normalized for area (MGVA). At 24 weeks, functional motor recovery was evaluated with isometric tetanic force (ITF) and compound muscle action potential (CMAP). MGVA data was compared with ITF and CMAP measurements by calculating the Spearman correlation coefficient. Muscle area (Left/Right Ratio (L/R)) of autografts was superior to allografts at 4, 12, 16, 20 and 24 weeks (p<0.03 for all comparisons). MGVs of the operated side were significantly higher for autografts at 4, 8, and 12 weeks and at 12, 16, 20, and 24 weeks for allografts (p<0.01 for all comparisons), compared to their unoperated sides. Similar patterns were seen in both groups for MGVA (operated versus control side). MGVA (L/R) demonstrated a strong correlation with ITF (L/R) for autografts (ρ = -0.7) and allografts (ρ = -0.87), but inconsistent with CMAPs (L/R). Quantitative muscle ultrasound demonstrated a reliable, non-invasive tool for evaluating motor recovery in a rabbit peroneal nerve reconstruction model. Clinical translation could provide valuable insights into muscle health and structural changes following nerve reconstruction.

Update/Refinement of Targeted Muscle Reinnervation Indication: A Scoping Review of Applications for Non-Amputees

Background: Targeted muscle reinnervation (TMR) was originally developed to enhance prosthetic control in amputees. However, it has also serendipitously demonstrated benefits in reducing phantom pain and neuromas. As a result, it has emerged as a secondary treatment for chronic neuromas in amputees and holds promise for managing neuropathic pain in non-amputee patients, particularly those with neuromas. This review synthesizes the current literature on TMR indications for non-amputee patients, highlighting its potential to address chronic peripheral nerve pain and neuromas beyond its original application in amputation. Methods: A thorough search of the PubMed and Cochrane databases up to January 2024 was conducted following the PRISMA guidelines. Inclusion criteria comprised case series, cohort studies, and randomized controlled trials reporting TMR outcomes in non-amputees. Results: Of 263 articles initially identified, 8 met the inclusion criteria after screening and full-text assessment. The articles were all case series with varied sample sizes and mainly focused on neuroma treatment (n = 6) and neuropathic pain management (n = 2) for both upper and lower extremities. Clinical studies included TMR efficacy for sural nerve neuromas in the lower extremities and hand neuromas, showing pain relief and improved function. Key findings were encouraging, showing successful pain relief, patient satisfaction, and psychosocial improvement, with only rare occurrences of complications such as motor deficits. Conclusions: In non-amputee patients, TMR appears to be a promising option for the surgical management of neuropathic pain, demonstrating favorable patient satisfaction and psychosocial outcomes along with low morbidity rates. Although functional improvements in gait recovery and range of motion are encouraging, further research will be important to confirm and expand upon these findings.

Regulation of neurotransmission in regenerating neuromuscular junctions involving endocannabinoids

The work was dedicated to investigation of the influence of two endocannabinoids – arachidonoylethanolamide (AEA), also known as anandamide, and 2-arachidonoylglycerol (2-AG) on the parameters of miniature endplate potentials (MEPP) and evoked endplate potentials (EPP) of motor synapses at the early stage of regeneration during muscle reinnervation. 2-AG increased the amplitude of MEPP by 35%, and also increased the amplitude of EPP by 37%, without affecting quantal content of EPP or any other parameters of neurotransmitter secretion. This effect was prevented by vesicular acetylcholine transporter inhibitor vesamicol and by inverse agonist of CB1-type cannabinoid receptors AM251. AEA did not change the amplitude or any other parameters of MEPP, but reduced the quantal content of EPP by 27%. The inhibitory effect of AEA was prevented by AM251 and by the L-type Ca2+ channel blocker nitrendipine. Thus, it was established for the first time that in newly formed motor synapses AEA and 2-AG activate the same type of presynaptic cannabinoid receptors, but have different final targets, influence different parameters of quantal ACh secretion and have multidirectional effects on synaptic transmission. The presence of both facilitatory and inhibitory effects of endocannabinoids in regenerating synapses may serve to fine-tune and regulate synaptic transmission during their maturation.

Early Postoperative Pain Course following Primary and Secondary Targeted Muscle Reinnervation: A Temporal Description of Pain Outcomes.

Targeted muscle reinnervation (TMR) is an effective surgical treatment of neuropathic pain for amputees. However, limited data exist regarding the early postoperative pain course for patients who undergo either primary (<14 days since amputation) or secondary (≥14 days) TMR. This study aims to outline the postoperative pain course for primary and secondary TMR during the first 6 postoperative months to aid in patient education and expectation management. Patients were eligible if they underwent TMR surgery between 2017 and 2023. Prospectively collected patient-reported outcome measures of pain scores, Pain Interference, and Pain Intensity were analyzed. Multilevel mixed-effects models were utilized to visualize and compare pain courses between primary and secondary TMR patients. A total of 203 amputees were included, with 40.9% being primary and 59.1% being secondary TMR patients. Primary TMR patients reported significantly lower pain scores over the full 6-month postoperative trajectory (p < 0.001) compared with secondary TMR patients, with a difference of Δ -1.0 at the day of TMR (primary = 4.5, secondary = 5.5), and a difference of Δ -1.4 at the 6-month mark (primary = 3.6, secondary = 5.0). Primary TMR patients also reported significantly lower Pain Interference (p < 0.001) and Pain Intensity scores (p < 0.001) over the complete trajectory of their care. Primary TMR patients report lower pain during the first 6 months postoperatively compared with secondary TMR patients. This may reflect how pre-existing neuropathic pain is more challenging to mitigate through peripheral nerve surgery. The current trends may assist in both understanding the postoperative pain course and managing patient expectations following TMR. Therapeutic - IV.

What to expect following targeted muscle reinnervation/regenerative peripheral nerve interface: Pain outcomes in an amputee population

Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI) have shown promise in improving and/or preventing neuropathic pain and reducing narcotic use in amputees. However, anecdotally, some patients experience an increase in pain in the first few months post-operatively. This study explored the pain trajectory of 22 upper and lower extremity amputees following their TMR and/or RPNI procedure in their first post-operative year, with a focus on the patterns of recovery the first few months. Our study found an overall decrease in the amount of pain and pain medication use at various time points post-operatively. Of note, several individuals had an increase in pain or required an increase in pain medications in the first three months. Different outcomes for patients who underwent primary versus secondary surgery were seen, which has been observed in other studies. Further prospective studies are warranted to evaluate these trends in pain after TMR or RPNI surgery in individuals with major limb amputations.

Technical Strategies and Learning Curve in Robotic-assisted Peripheral Nerve Surgery.

Robotic-assisted peripheral nerve surgery (RASPN) has emerged as a promising advancement in microsurgery, offering enhanced precision and tremor reduction for nerve coaptations. This study investigated the largest published patient collective in RASPN and provided specific technical aspects, operative setups, and a learning curve. Data collection involved creating a prospective database that recorded surgical details such as surgery type, duration, nerve coaptation time, and number of stitches. The experienced surgeon first underwent a 12-hour training program utilizing the Symani robot system in combination with optical magnification tools before using the system clinically. The study included 19 patients who underwent robot-assisted peripheral nerve reconstruction. The cohort included six men (31.6%) and 13 women (68.4%), with an average age of 53.8 ± 18.4 years. The procedures included nerve transfers, targeted muscle reinnervation, neurotized free flaps, and autologous nerve grafts. Learning curve analysis revealed no significant reduction in time per stitch over the initial nine coaptations (4.9 ± 0.5 min) compared with the last 10 coaptations (5.5 ± 1.5 min). The learning curve for RASPN was compared with early experiences with other surgical robots, emphasizing the importance of surgical proficiency and assistant training. Obstacles such as instrument grip strength and blood clot formation were highlighted, and suggestions for future advancements were proposed. RASPN presents an exciting opportunity to enhance precision; however, ongoing research and optimization are necessary to fully harness its benefits.

Buried filet of limb flaps for the reconstruction of forequarter and hindquarter amputations.

Forequarter and hindquarter amputations have traditionally been closed with local tissues, but the technique is plagued by a high rate of complication such as marginal necrosis, seroma, infection, and dehiscence. Filet of limb flaps have been used when local tissues are insufficient for closure, and despite their use in more extensive and complex wounds, outcomes seem to be better in these cases. Recognizing that filet of limb flaps not only serve to cover the wound, but also eliminate dead space, supplement at-risk and/or radiated tissue, pad underlying hard structures, and facilitate neuroma prevention with target muscle reinnervation, we have change our practice to utilize buried filet of limb flaps even when local tissues are technically "sufficient" to close the wound. The purpose of this article to organize and describe the ways in which buried filet-of-limb flaps can be used to achieve important and discrete surgical objectives in forequarter and hindquarter amputation, and to facilitate increased recognition of collaborative interdisciplinary opportunities for spare-part reconstruction. Retrospective data from the medical records of seven patients, collected between 2010 to 2023 at our single tertiary referral center, were reviewed. This included all patients for whom a buried (or partially buried) filet of limb flap was attempted for forequarter or hindquarter amputation reconstruction. Five males and two females ranging 55 to 75 years of age, met the inclusion criteria. Three cases of forequarter amputation and four cases of hindquarter amputation were included. Six flaps were successfully transferred without major flap-related complications. The mean follow-up period was eight and a half months. Even when local tissues are technically "sufficient" to close forequarter and hindquarter amputation wounds, we have found buried filet of limb flaps to be useful in several ways. These include occupying dead space, providing double-layer coverage, padding hard structures, preventing neuromas, and reconstructing sacro- and spino-pelvic continuity. Our approach emphasizes interdisciplinary collaboration and highlights the potential advantages of buried filet of limb flaps in optimizing patient outcomes for complex limb amputations.

Ultrasound to guide nerve transfer healing and muscle re-innervation

Nerve transfer and muscle re-innervation are critical components for restoring function and managing brachial plexus injuries. This technical note highlights the role of ultrasound in assessing the success of a nerve transfer after the surgical procedure. By visualizing the nerve transfer site and evaluating muscle response to stimulation, ultrasound can help confirm that the transferred nerve is healing and re-innervating the target muscle. This report highlights the effectiveness of ultrasound in the early diagnosis and monitoring of nerve re-innervation and muscle recovery.

Peripheral Nerve Blocks as a Predictor of Nerve Reconstruction Success After Major Limb Amputation.

Postamputation pain is a spectrum of debilitating sensations that impacts millions of people in the United States. While the development of postamputation pain, including phantom limb pain (PLP), is multifactorial, it has been associated with disorganized axonal sprouting, resulting in a neuroma and subsequent central nervous system changes. Nerve reconstruction surgeries, such as regenerative peripheral nerve interface (RPNI) and targeted muscle reinnervation (TMR), provide transected nerve fibers with proper target organs for reinnervationand have been shown to significantly reduce PLP. This case series aims to describe perioperative peripheral nerve blocks as a diagnostic tool for identifying patients who would benefit from RPNI or TMR. We conducted a retrospective search of patients who underwent major extremity amputation and who received a diagnostic peripheral nerve block before undergoing reconstructive nerve surgery (TMR and/or RPNI). Six patients (58-80 years old) with below-knee amputations (BKA) were examined. All patients experienced a reduction in postamputation pain (PAP), specifically PLP, after a diagnostic peripheral nerve block (PNB). The average time between amputation and revision surgery was approximately two years (Mean: 22.35 months). Following surgical intervention, all patientsreported a reduction in PLP episodes after nerve reconstruction surgery. Two patients no longer reported PLP.Ambulation rates also improved following revision (50% vs 83%). PNBs can be used as an effective diagnostic tool to identify patients that will significantly benefit from amputation revisions with TMR or RPNI.

VEGF, but Not BDNF, Prevents the Downregulation of KCC2 Induced by Axotomy in Extraocular Motoneurons.

The potassium-chloride cotransporter KCC2 is the main extruder of Cl- in neurons. It plays a fundamental role in the activity of the inhibitory neurotransmitters (GABA and glycine) since low levels of KCC2 promote intracellular Cl- accumulation, leading to the depolarizing activity of GABA and glycine. The downregulation of this cotransporter occurs in neurological disorders characterized by hyperexcitability, such as epilepsy, neuropathic pain, and spasticity. KCC2 is also downregulated after axotomy. If muscle reinnervation is allowed, the KCC2 levels recover in motoneurons. Therefore, we argued that target-derived neurotrophic factors might be involved in the regulation of KCC2 expression. For this purpose, we performed the axotomy of extraocular motoneurons via the monocular enucleation of adult rats, and a pellet containing either VEGF or BDNF was chronically implanted in the orbit. Double confocal immunofluorescence of choline acetyl-transferase (ChAT) and KCC2 was carried out in the brainstem sections. Axotomy led to a KCC2 decrease in the neuropil and somata of extraocular motoneurons, peaking at 15 days post-lesion, with the exception of the abducens motoneuron somata. VEGF administration prevented the axotomy-induced KCC2 downregulation. By contrast, BDNF either maintained or reduced the KCC2 levels following axotomy, suggesting that BDNF is involved in the axotomy-induced KCC2 downregulation in extraocular motoneurons. The finding that VEGF prevents KCC2 decrease opens up new possibilities for the treatment of neurological disorders coursing with neuronal hyperactivity due to KCC2 downregulation.

Managing Major Peripheral Nerves in Forearm-Level Amputations With TMR and RPNI: What's the Best Recipe?

Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) prevent symptomatic neuroma formation in amputees. Forearm-level amputations present multiple muscular targets, making it challenging to determine the ideal treatment. The purpose of this study was to evaluate the best TMR targets, role of RPNI, and appropriate patient-selection criteria in forearm-level amputations. We hypothesized that deep and distal TMR targets would best prevent symptomatic neuromas, RPNI would prove a success adjunct, and patients with poorly controlled diabetes would not develop symptomatic neuromas regardless of nerve management. We retrospectively identified forearm-level amputations performed between 2017 and 2022. Patients with TMR by outside providers, follow-up <6 months, or insufficient documentation were excluded. Demographics, surgical nerve management, and postoperative complications were collected. The primary outcome was development of a painful neuroma determined by the Eberlin criteria. Patients undergoing TMR were divided a priori into two groups, superficial and proximal versus deep and distal TMR targets, and were compared. Thirty-nine patients met inclusion criteria, and 16 developed a symptomatic neuroma. No patients with a deep or distal TMR target developed a symptomatic neuroma. One nerve out of 12 treated with RPNI developed a symptomatic neuroma. No patient with poorly controlled diabetes developed a symptomatic neuroma, despite no advanced nerve management. In a case series of forearm amputations, deep and distal TMR targets prevented symptomatic neuroma formation more than superficial and proximal targets. Regenerative peripheral nerve interface is a useful adjunct for neuroma control, especially for the radial sensory nerve. Patients with poorly controlled diabetes may not require advanced nerve management. Level IV retrospective case series.