Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

Classifying the Severity of Cubital Tunnel Syndrome: A Preoperative Grading System Incorporating Electrodiagnostic Parameters.

BACKGROUND: Current classifications for cubital tunnel syndrome have not been shown to reliably predict postoperative outcomes. In this article, the authors introduce a new classification that incorporates clinical and electrodiagnostic parameters, including compound muscle action potential amplitude, to classify the preoperative severity of cubital tunnel syndrome. The authors compare this to established classifications and evaluate its association with patient-rated improvement. METHODS: The authors reviewed 44 patients who were treated surgically for cubital tunnel syndrome. Patients were retrospectively classified using their proposed classification and the Akahori, McGowan-Goldberg, Dellon, and Gu classifications. Correlation of grades was assessed by Spearman coefficients and agreement was assessed by weighted kappa coefficients. Patient-reported impairment was assessed using the Disabilities of the Arm, Shoulder, and Hand questionnaire before and after surgery. RESULTS: The classifications tended to grade patients in a similar way, with Spearman coefficients of 0.60 to 0.85 ( p < 0.0001) and weighted kappa coefficients of 0.46 to 0.71 ( p < 0.0001). Preoperative Disabilities of the Arm, Shoulder, and Hand scores increased with severity grade for most classifications. In multivariable analysis, the authors' classification predicted postoperative Disabilities of the Arm, Shoulder, and Hand score improvement, whereas established classifications did not. CONCLUSIONS: Established classifications are imperfect indicators of preoperative severity. The authors introduce a preoperative classification for cubital tunnel syndrome that incorporates electrodiagnostic findings in addition to classic signs and symptoms. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, III.

Are Perforators Reliable as Recipient Arteries in Lower Extremity Reconstruction? Analysis of 423 Free Perforator Flaps.

BACKGROUND: Perforator flaps have revolutionized lower limb reconstruction by offering single-stage thin, pliable coverage with an excellent aesthetic match. Although anastomosis of the flap to a major artery remains the gold standard, perforator-to-perforator anastomosis has several advantages, including expedient recipient dissection and increased recipient options in vessel-depleted extremities. The aim of this study was to compare flap survival when a perforator or major artery was used as a recipient vessel. METHODS: A retrospective cohort of free perforator flaps for lower limb reconstruction was reviewed. Demographics, comorbidities, vascular status, defect characteristics, operative details, and complications were recorded. Outcomes for perforator and major artery recipients were compared. RESULTS: Four hundred twenty-three flaps were performed for various reasons using perforator flaps. The total limb salvage rate was 98.8 percent. Total and partial flap failure rates were 6.1 percent and 9.0 percent, respectively. Comparing perforator recipients [n = 109 (25.8 percent)] to major artery recipients [n = 314 (74.2 percent)], there was no significant difference in total (p = 0.746) or partial flap failure (p = 0.212). Significant factors between the groups included larger flap size with major artery recipients (p = 0.001) and shorter operative time when using a perforator recipient (p = 0.012). CONCLUSIONS: Perforator-to-perforator anastomosis is a reliable option that affords equivalent rates of flap success compared to major artery anastomosis in lower extremity reconstruction. The authors advocate using a major artery recipient in defects where the axial vessels are easily accessible. A perforator recipient is a viable alternative in defects where access to the axial vessels is inconvenient and in patients with limited recipient options. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Femoral nerve decompression and sartorius-to-quadriceps nerve transfers for partial femoral nerve injury: a cadaveric study and early case series.

OBJECTIVE: Partial femoral nerve injuries cause significant disability with ambulation. Due to their more proximal and superficial location, sartorius branches are often spared in femoral nerve injuries. In this article, the authors report the benefits of femoral nerve decompression, demonstrate the feasibility of sartorius-to-quadriceps nerve transfers in a cadaveric study, describe the surgical technique, and report clinical results. METHODS: Four fresh-frozen cadaveric lower limbs were dissected for anatomical analysis of the sartorius nerve. In addition, a retrospective review of patients with partial femoral nerve injuries treated with femoral nerve decompression and sartorius-to-quadriceps nerve transfers was conducted. Pre- and postoperative knee extension Medical Research Council (MRC) grades and pain scores (visual analog scale) were collected. RESULTS: Up to 6 superficial femoral branches innervate the sartorius muscle just distal to the inguinal ligament. Each branch yielded an average of 672 nerve fibers (range 99-1850). Six patients underwent femoral nerve decompression and sartorius-to-quadriceps nerve transfers. Four patients also had concomitant obturator-to-quadriceps nerve transfers. At final follow-up (average 13.4 months), all patients achieved MRC grade 4-/5 or greater knee extension. The average preoperative pain score was 5.2, which decreased to 2.2 postoperatively (p = 0.03). CONCLUSIONS: Femoral nerve decompression and nerve transfer using sartorius branches are a viable tool for restoring function in partial femoral nerve injuries. Sartorius branches serve as ideal donors in quadriceps nerve transfers because they are expendable, are close to their recipients, and have an adequate supply of nerve fibers.

Postsurgical Electrical Stimulation Enhances Recovery Following Surgery for Severe Cubital Tunnel Syndrome: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Patients with severe cubital tunnel syndrome often have poor functional recovery with conventional surgical treatment. Postsurgical electrical stimulation (PES) has been shown to enhance axonal regeneration in animal and human studies. OBJECTIVE: To determine if PES following surgery for severe cubital tunnel syndrome would result in better outcomes compared to surgery alone. METHODS: Patients with severe cubital tunnel syndrome in this randomized, double-blind, placebo-controlled trial were randomized in a 1:2 ratio to the control or stimulation groups. Control patients received cubital tunnel surgery and sham stimulation, whereas patients in the stimulation group received 1-h of 20 Hz PES following surgery. Patients were assessed by a blinded evaluator annually for 3 yr. The primary outcome was motor unit number estimation (MUNE) and secondary outcomes were grip and key pinch strength and McGowan grade and compound muscle action potential. RESULTS: A total of 31 patients were enrolled: 11 received surgery alone and 20 received surgery and PES. Three years following surgery, MUNE was significantly higher in the PES group (176 ± 23, mean + SE) compared to controls (88 ± 11, P < .05). The mean gain in key pinch strength in the PES group was almost 3 times greater than in the controls (P < .05). Similarly, other functional and physiological outcomes showed significantly greater improvements in the PES group. CONCLUSION: PES enhanced muscle reinnervation and functional recovery following surgery for severe cubital tunnel syndrome. It may be a clinically useful adjunct to surgery for severe ulnar neuropathy, in which functional recovery with conventional treatment is often suboptimal.

Refining Indications for the Supercharge End-to-Side Anterior Interosseous to Ulnar Motor Nerve Transfer in Cubital Tunnel Syndrome.

The supercharge end-to-side anterior interosseous to ulnar motor nerve transfer has gained popularity over the past decade as a method of augmenting intrinsic muscle reinnervation in patients with acute neurotmetic ulnar nerve injuries. Controversy remains regarding its efficacy and appropriate clinical indications in cubital tunnel syndrome, where the timing of onset of axonal loss is less clear. The authors present guidelines for patient selection, surgical technique, and postoperative rehabilitation based on their clinical experience with the technique in this patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, V.

The Triceps Traction Test: A Decision Tool for the Choice of Stabilizing Flap After In Situ Decompression of the Ulnar Nerve.

PURPOSE: Recent evidence demonstrates that in situ decompression has comparable outcomes to other surgical techniques for cubital tunnel syndrome. However, this technique does not address the instability of the ulnar nerve, a common indication to transpose the ulnar nerve. Transposition of the ulnar nerve can potentially devascularize the ulnar nerve, stabilizing flaps block subluxation of the ulnar nerve and thereby negate the need for transposition. Flaps originating from the triceps and the flexor-pronator fascia could be used to stabilize the ulnar nerve. Herein, we present a novel intraoperative test, the "triceps traction test" and our algorithm for choosing a stabilizing flap when ulnar nerve instability is encountered after in situ decompression.

Cross-Palm Nerve Grafts to Enhance Sensory Recovery in Severe Ulnar Neuropathy.

Background: Intrinsic atrophy and debilitating sensory loss are prominent features of severe ulnar neuropathy with limited surgical options to reliably improve recovery. Restoration of sensation is important to provide protection for the vulnerable ulnar border of the hand. Here, we report our experience with side-to-side sensory nerve grafting from the median to ulnar nerve in the palm to enhance ulnar sensory recovery. Methods: A retrospective chart review identified patients with severe ulnar neuropathy who underwent cross-palm nerve grafting. Included patients had objective loss of protective sensation in the ulnar distribution with 2-point discrimination >8 mm, Semmes-Weinstein monofilament testing (SWMT) >4.56, or no sensory response on nerve conduction testing. Cross-palm side-to-side tension-free grafting from median to ulnar sensory components was performed using short-segment allograft or autografts. Analysis included patient etiology, procedures, nerve conduction studies, objective sensory testing, and Disabilities of the Arm, Shoulder, and Hand Disability score. Results: Forty-eight patients with severe ulnar neuropathy underwent cross-palm nerve grafting between 2014 and 2017. Twenty-four patients had adequate follow-up for inclusion. Of the 24 patients, 21 (87%) had return of protective sensation, 16 (66.7%) had return of diminished light touch sensation, and 6 (25%) had return to normal range sensation within 1 year as assessed by SWMT and/or 2-point discrimination. Patients treated with autograft demonstrated referred sensation to the median nerve distribution. Conclusions: Cross-palm nerve grafting may be a useful adjunct to enhance sensory recovery in severe ulnar neuropathy. Further study to quantify differences in sensory recovery between traditional operative techniques and cross-palm nerve grafting is required.

Algorithm for Free Perforator Flap Selection in Lower Extremity Reconstruction Based on 563 Cases.

BACKGROUND: Microsurgical lower extremity reconstruction remains a challenge. The use of perforator flaps in lower extremity reconstruction is expanding. The authors present an algorithm to guide in the selection of the ideal free perforator flap that can be tailored to each lower extremity defect. METHODS: The authors conducted a retrospective review of lower extremity reconstruction using free perforator flaps over a 7-year period. Demographics, comorbidities, defect characteristics, operative details, complications, and secondary procedures were documented. Pairwise comparisons of flap types were performed to differentiate flaps on the basis of flap size, thickness, and pedicle length. RESULTS: A total of 563 free perforator flaps were performed. The most common causes were trauma (36.5 percent) and diabetes (24.4 percent). Nine flaps were used, with the most common being superficial circumflex iliac perforator (51.2 percent) and anterolateral thigh (33.2 percent). Size differed significantly between flap types (p < 0.05), with the exception of thoracodorsal artery perforator versus gluteal artery perforator flaps (p = 0.26). The thinnest flaps were posterior interosseous artery perforator (3.7 ± 0.5 mm) and superficial circumflex iliac perforator (5.4 ± 0.8 mm). The thickest flaps were deep inferior epigastric perforator (11.1 ± 3.9 mm) and anterolateral thigh (9.0 ± 1.5 mm). The shortest pedicles were in posterior interosseous artery perforator (3.3 ± 0.3 cm) and superficial circumflex iliac perforator flaps (5.2 ± 0.8 cm). The longest pedicles were in deep inferior epigastric perforator (11.7 ± 1.4 cm), thoracodorsal artery perforator (9.3 ± 1.4 cm), and anterolateral thigh flaps (9.2 ± 0.8 cm). CONCLUSIONS: Free perforator flaps are reliable in lower extremity reconstruction. The authors believe their algorithm for flap selection helps to optimize form and function, decrease operative time, and minimize donor-site morbidity and secondary procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Bone Transport Distraction Osteogenesis in the Reconstruction of Pediatric Posttraumatic Calvarial Defects.

Reconstruction of posttraumatic calvarial bone defects in pediatric patients is a challenge due to the growing brain and limited autogenous bone supply. Traditional techniques such as split calvarial and particulate bone grafts are associated with prolonged operative time and significant blood loss, which is a major concern in children under the age of 3 years. Bone transport distraction osteogenesis has proven efficacy and safety in the reconstruction of other craniofacial deformities. This procedure is less invasive and requires shorter operative times and hospital stay. We report our experience with 2 cases of bone transport distraction osteogenesis for the reconstruction of large posttraumatic calvarial defects in pediatric patients.

Differences in Opioid Prescribing Practices among Plastic Surgery Trainees in the United States and Canada.

BACKGROUND: Overprescribing following surgery is a known contributor to the opioid epidemic, increasing the risk of opioid abuse and diversion. Trainees are the primary prescribers of these medications at academic institutions, and little is known about the factors that influence their prescribing. The authors hypothesized that differences in health care funding and delivery would lead to disparities in opioid prescribing. Therefore, the authors sought to compare the prescribing practices of plastic surgery trainees in the United States and Canada. METHODS: A survey was administered to trainees at a sample of U.S. and Canadian institutions. The survey queried opioid-prescriber education, factors contributing to prescribing practices, and analgesic prescriptions written after eight procedures. Oral morphine equivalents were calculated for each procedure and compared between groups. RESULTS: One hundred sixty-two trainees completed the survey, yielding a response rate of 32 percent. Opioid-prescriber education was received by 25 percent of U.S. and 53 percent of Canadian trainees (p < 0.0001). Preoperative counseling was performed routinely by only 11 percent of U.S. and 14 percent of Canadian trainees. U.S. trainees prescribed significantly more oral morphine equivalents than Canadians for seven of eight procedures (p < 0.05). Residency training in the United States and junior training level independently predicted higher oral morphine equivalents prescribed (p < 0.05). CONCLUSIONS: U.S. trainees prescribed significantly more opioids than their Canadian counterparts for seven of eight procedures surveyed. Many trainees are missing a valuable opportunity to provide opioid counseling to patients. Standardizing trainee education may represent an opportunity to reduce overprescribing.

Compound Muscle Action Potential Amplitude Predicts the Severity of Cubital Tunnel Syndrome.

BACKGROUND: Cubital tunnel syndrome has a spectrum of presentations ranging from mild paresthesias to debilitating numbness and intrinsic atrophy. Commonly, the classification of severity relies on clinical symptoms and slowing of conduction velocity across the elbow. However, changes in compound muscle action potential (CMAP) amplitude more accurately reflect axonal loss. We hypothesized that CMAP amplitude would better predict functional impairment than conduction velocity alone. METHODS: A retrospective cohort of patients who underwent a surgical procedure for cubital tunnel syndrome over a 5-year period were included in the study. All patients had electrodiagnostic testing performed at our institution. Clinical and electrodiagnostic variables were recorded. The primary outcome was preoperative functional impairment, defined by grip and key pinch strength ratios. Multivariable regression identified which clinical and electrodiagnostic variables predicted preoperative functional impairment. RESULTS: Eighty-three patients with a mean age of 57 years (75% male) were included in the study. The majority of patients (88%) had abnormal electrodiagnostic studies. Fifty-four percent had reduced CMAP amplitude, and 79% had slowing of conduction velocity across the elbow (recorded from the first dorsal interosseous). On bivariate analysis, older age and longer symptom duration were significantly associated (p < 0.05) with reduced CMAP amplitude and slowing of conduction velocity across the elbow, whereas body mass index (BMI), laterality, a primary surgical procedure compared with revision surgical procedure, Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire scores, and visual analog scale (VAS) scores for pain were not. Multivariable regression analysis demonstrated that reduced first dorsal interosseous CMAP amplitude independently predicted the loss of preoperative grip and key pinch strength and that slowed conduction velocity across the elbow did not. CONCLUSIONS: Reduced first dorsal interosseous amplitude predicted preoperative weakness in grip and key pinch strength, and isolated slowing of conduction velocity across the elbow did not. CMAP amplitude is a sensitive indicator of axonal loss and an important marker of the severity of cubital tunnel syndrome. It should be considered when counseling patients with regard to their prognosis and determining the necessity and timing of operative intervention. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Comparing the Efficacy of Triple Nerve Transfers with Nerve Graft Reconstruction in Upper Trunk Obstetric Brachial Plexus Injury.

BACKGROUND: Upper trunk obstetric brachial plexus injury can cause profound shoulder and elbow dysfunction. Although neuroma excision with interpositional sural nerve grafting is the current gold standard, distal nerve transfers have a number of potential advantages. The goal of this study was to compare the clinical outcomes and health care costs between nerve grafting and distal nerve transfers in children with upper trunk obstetric brachial plexus injury. METHODS: In this prospective cohort study, children who underwent triple nerve transfers were followed with the Active Movement Scale for 2 years. Their outcomes were compared to those of children who underwent nerve graft reconstruction. To assess health care use, a cost analysis was also performed. RESULTS: Twelve patients who underwent nerve grafting were compared to 14 patients who underwent triple nerve transfers. Both groups had similar baseline characteristics and showed improved shoulder and elbow function following surgery. However, the nerve transfer group displayed significantly greater improvement in shoulder external rotation and forearm supination 2 years after surgery (p < 0.05). The operative time and length of hospital stay were significantly lower (p < 0.05), and the overall cost was approximately 50 percent less in the nerve transfer group. CONCLUSION: Triple nerve transfer for upper trunk obstetric brachial plexus injury is a feasible option, with better functional shoulder external rotation and forearm supination, faster recovery, and lower cost compared with traditional nerve graft reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Improving peripheral nerve regeneration: from molecular mechanisms to potential therapeutic targets.

Peripheral nerve injury is common especially among young individuals. Although injured neurons have the ability to regenerate, the rate is slow and functional outcomes are often poor. Several potential therapeutic agents have shown considerable promise for improving the survival and regenerative capacity of injured neurons. These agents are reviewed within the context of their molecular mechanisms. The PI3K/Akt and Ras/ERK signaling cascades play a key role in neuronal survival. A number of agents that target these pathways, including erythropoietin, tacrolimus, acetyl-l-carnitine, n-acetylcysteine and geldanamycin have been shown to be effective. Trk receptor signaling events that up-regulate cAMP play an important role in enhancing the rate of axonal outgrowth. Agents that target this pathway including rolipram, testosterone, fasudil, ibuprofen and chondroitinase ABC hold considerable promise for human application. A tantalizing prospect is to combine different molecular targeting strategies in complementary pathways to optimize their therapeutic effects. Although further study is needed prior to human trials, these modalities could open a new horizon in the clinical arena that has so far been elusive.

Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence.

Intermuscular coherence analysis can be used to assess the common drive to muscles. Coherence in the beta-frequency band (15-35 Hz) is thought to arise from common cortical sources. Intermuscular coherence analysis is a potentially attractive tool for the investigation of motor cortical excitability changes because it is non-invasive and can be done relatively quickly. We carried out this study to test the hypothesis that intermuscular coherence analysis was able to detect cortical excitability changes in healthy subjects following transcranial direct current stimulation (tDCS). tDCS has been shown to increase (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle potential evoked by TMS. We found that anodal tDCS caused an increase in motor evoked potential (MEP) size that was paralleled by an increase in beta-band intermuscular coherence. Similarly, the reduction in MEP size produced by cathodal tDCS was paralleled by a reduction in beta-band intermuscular coherence, while sham stimulation did not result in any change in either MEP amplitude or beta-band intermuscular coherence. The similar pattern of change observed for MEP and intermuscular coherence may indicate similar mechanisms of action, although this cannot be assumed without further investigation. These changes do suggest that at least some of the action of tDCS is on cortical networks, and that combined tDCS and intermuscular coherence analysis may be useful in the diagnosis of pathologies affecting motor cortical excitability.