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.

Combined Targeted Muscle Reinnervation With Regenerative Peripheral Nerve Interfaces Decreases Long-Term Narcotic Use in Amputees: A Case Control Study.

PURPOSE: Combined targeted muscle reinnervation with regenerative peripheral nerve interfaces ("TMRpni") is a recently described nerve management strategy that leverages beneficial elements of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) techniques. This study aimed to evaluate the effect of TMRpni on long-term opioid consumption after amputation. We hypothesize that TMRpni decreases chronic opioid consumption in amputees. METHODS: This is a retrospective cohort study of all patients who underwent TMRpni between 2019 and 2021. These patients were age-matched at a 1:1 ratio with a control group of patients who underwent amputation without TMRpni. Statistical analysis was performed using SPSS Version 28.0. RESULTS: Thirty-one age-matched pairs of patients in the TMRpni and control groups were included. At 30 days after surgery, there was no significant difference in number of patients who required an additional refill of their opioid prescriptions (45% vs 55%, P = 0.45) or patients who continued to actively use opioids (36% vs 42%, P = 0.60). However, at 90 days after surgery, there was a significantly lower number of patients from the TMRpni group who reported continued opioid use compared with the control group (10% vs 32%, P = 0.03). CONCLUSIONS: This study demonstrates that TMRpni may translate to decreased rates of chronic opiate use. Continued study is indicated to optimize TMRpni techniques and patient selection and to determine its long-term efficacy.

Adipofascial Perforator Flaps for Peripheral Nerve Resurfacing after External Neurolysis.

Background: External neurolysis is an important approach to treating symptomatic peripheral nerve entrapment. In cases of recurrent neurolysis or particularly extensive neurolysis, a paucity of overlying soft tissue for closure over the freshly liberated nerve presents a challenge to long-term surgical success as primary closure of this tissue may predispose the patient to recalcitrant epineural scarring. We report the intermediate term outcomes of the use of adipofascial perforator flaps as a means of vascularised tissue resurfacing of nerves in these difficult scenarios. Methods: We retrospectively reviewed patients undergoing external neurolysis for painful peripheral nerve lesions who subsequently had soft tissue reconstruction with local adipofascial flaps. Data with regard to age, gender, limb involved, duration of symptoms, number of prior surgeries, operative time, type of flap, vascular basis of flap, duration of follow-up, visual analogue pain score, monofilament sensory testing and complications were collected. Results: We included six patients (four women) with a minimum follow-up period of 17 months (range: 17-25 months). Age ranged from 39 to 60 years of age. Four cases involved the upper extremity and two the lower extremity. Symptoms had been present between 1 and 10 years. All operations utilised a local adipofascial flap perfused by a named perforating vessel emanating from an adjacent axial vessel. Operative time for flap creation and inset was 74 minutes, on average. There was one minor complication owing to superficial wound dehiscence. All patients reported substantial pain relief (≥five-point reduction on visual analogue scale; scores 0-3 at last follow-up) and objective sensory testing demonstrated improvement. Conclusions: Our report pays particular attention to surgical technique that is applicable to both upper and lower extremities in addition to intermediate term safety and pain outcomes. Level of Evidence: Level IV (Therapeutic).

["Nerve Surgery" In German-Speaking Countries - Starting With The Nerve Club Up To A Certificate]. / "Nervenchirurgie" im deutschsprachigen Raum ­ vom NervClub zum Zertifikat.

We present the Nerve Club, a community of colleagues originating from german-speaking countries and dedicated to those working in or outside surgery with interest in the peripheral nerve. This article reviews the club´s history and specific characteristics and activities, and highlights the concept of a certificate in nerve surgery. We have annual club meetings and organize every two years a plexus symposium. Also exists a scientific publication award and cooperation with an online based journal dedicated to medical publications in the field of nerve surgery.

[Nerve Transfers in Peripheral Nerve Lesions]. / Nerventransfers bei peripheren Nervenläsionen.

BACKGROUND: Lesions of peripheral nerves of the upper extremities often lead to persistent, serious limitations in motor function and sensory perception. Affected patients suffer from both private and professional restrictions associated with long-term physical, psychological and socioeconomic consequences. INDICATION: An early indication for a nerve transfer shortens the reinnervation distance and improves the growing of motor and sensory axons into the target organ to facilitate early mobility and sensitivity. When planning the timepoint of the surgical procedure, the distance to be covered by reinnervation as well as the morbidities of donor nerves must be considered individually. RESULTS: Nerve transfers can achieve earlier and safer reinnervation to improve motor and sensory functions after nerve injuries in the upper extremity.

Usability of Nerve Tape: A Novel Sutureless Nerve Coaptation Device.

PURPOSE: Microsuture neurorrhaphy is technically challenging and has inherent drawbacks. This study evaluated the potential of a novel, sutureless nerve coaptation device to improve efficiency and precision. METHODS: Twelve surgeons participated in this study-six attending hand/microsurgeons and six trainees (orthopedic and plastic surgery residents or hand surgery fellows). Twenty-four cadaver arm specimens were used, and nerve repairs were performed at six sites in each specimen-the median and ulnar nerves in the proximal forearm, the median and ulnar nerves in the distal forearm, and the common digital nerves to the second and third web spaces. Each study participant performed nerve repairs at all six injury locations in two different cadaver arms (n = 12 total repairs for each participating surgeon). The nerve repairs were timed, tested for tensile strength, and graded for alignment and technical repair quality. RESULTS: A substantial reduction in time was required to perform repairs with the novel coaptation device (1.6 ± 0.8 minutes) compared with microsuture (7.2 ± 3.6 minutes). Device repairs were judged clinically acceptable (scoring "Excellent" or "Good" by most of the expert panel) in 97% of the repairs; the percentage of suture repairs receiving Excellent/Good scores by most of the expert panel was 69.4% for attending surgeons and 36.1% for trainees. The device repairs exhibited a higher average peak tensile force (7.0 ± 3.6 N) compared with suture repairs (2.6 ± 1.6 N). CONCLUSIONS: Nerve repairs performed with a novel repair device were performed faster and with higher technical precision than those performed using microsutures. Device repairs had substantially greater tensile strength than microsuture repairs. CLINICAL RELEVANCE: The evaluated novel nerve repair device may improve surgical efficiency and nerve repair quality.

The impact of SARS-Covid-19 pandemic on peripheral nerve surgery - A single centre report.

OBJECTIVE: SARS-Cov-19 pandemic totally changed daily routine work in German hospitals. As hospital capacity was reduced, many surgeries were postponed or even cancelled. On March 25th 2020 the German Society of Neurosurgery (DGNC) published a statement in which urgent non-elective surgeries were defined for each neurosurgical domain, whereas elective interventions were deferred. The present work examines the impact of these Covid strategies focusing on patients with peripheral lesions who were conducted to our department during this period of time. METHODS: All patients who underwent any peripheral nerve surgery at our department from January 2018 until December 2022, were included. The complete range of surgeries including peripheral nerve lesions was examined encompassing compression syndromes, traumatic lesions of brachial plexus, traumatic lesions and tumors of single peripheral nerves. The numbers of surgical procedures were compared before, during and after pandemic. Pearson correlation coefficient was analysed. RESULTS: From 2018 to 2022 the total number of surgical procedures involving peripheral nerves included 2422 procedures. Compression syndromes made up the largest proportion (1433 operations, 59%), followed by peripheral nerve lesions (445 operations, 18%), peripheral nerve tumors (344 operations, 14%) and lesions of the brachial plexus (142 operations, 6%). The average was 40,5 interventions per month, the range was 7-63. Two declines in the number of peripheral nerve surgeries were noted during this period. The first was in April and May 2020 with an average drop of 65% and 41% respectively. In these months the average number of operations was 37. The second decrease was from October 2021 until January 2022, where number of surgeries was reduced by 16%, 36%, 83% and 18% with an average number of 50 operations. Both declines showed a significant and strong correlation with the lower number of compression syndrome treatments (r = 0.952, p < 0.001 and r = 0.968, p < 0.001), while no drop and no significant correlation was found in the treatment of traumatic peripheral nerve injuries (p = 0.769, r = 0.095 and p = 0.243, r = 0.366) and traumatic brachial plexus injuries (p = 0.787, r = 0.088 and p = 0.780, r = 0.09). A weak significant correlation was seen in the treatment numbers of peripheral nerve tumors (p = 0.017, r = 0.672 and p = 0.015, r = 0.67). CONCLUSION: Covid-19 pandemic lead to a significant decrease in the number of nerve decompressions, since, according to the German Society of Neurosurgery, those were considered as elective surgeries.

Sticky and Strain-Gradient Artificial Epineurium for Sutureless Nerve Repair in Rodents and Nonhuman Primates.

The need for the development of soft materials capable of stably adhering to nerve tissues without any suturing followed by additional damages is at the fore at a time when success in postoperative recovery depends largely on the surgical experience and/or specialized microsuturing skills of the surgeon. Despite fully recognizing such prerequisite conditions, designing the materials with robust adhesion to wet nerves as well as acute/chronic anti-inflammation remains to be resolved. Herein, a sticky and strain-gradient artificial epineurium (SSGAE) that overcomes the most critically challenging aspect for realizing sutureless repair of severely injured nerves is presented. In this regard, the SSGAE with a skin-inspired hierarchical structure entailing strain-gradient layers, anisotropic Janus layers including hydrophobic top and hydrophilic bottom surfaces, and synergistic self-healing capabilities enables immediate and stable neurorrhaphy in both rodent and nonhuman primate models, indicating that the bioinspired materials strategy significantly contributes to translational medicine for effective peripheral nerve repair.

Nerve Capping Techniques for Neuroma Management: A Comprehensive Literature Review.

BACKGROUND/AIM OF THE STUDY: Nerve capping is a method of neuroma treatment or prevention that consists of the transplantation of a proximal nerve stump into an autograft or other material cap, after surgical removal of the neuroma or transection of the nerve. The aim was to reduce neuroma formation and symptoms by preventing neuronal adhesions and scar tissue. In this narrative literature review, we summarize the studies that have investigated the effectiveness of nerve capping for neuroma management to provide clarity and update the clinician's knowledge on the topic. METHODS: A systematic electronic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was performed in the PubMed database combining "neuroma," "nerve," "capping," "conduit," "treatment," "management," "wrap," "tube," and "surgery" as search terms. English-language clinical studies on humans and animals that described nerve capping as a treatment/prevention technique for neuromas were then selected based on a full-text article review. The data from the included studies were compiled based on the technique and material used for nerve capping, and technique and outcomes were reviewed. RESULTS: We found 10 applicable human studies from our literature search. Several capping materials were described: epineurium, nerve, muscle, collagen nerve conduit, Neurocap (synthetic copolymer of lactide and caprolactone, which is biocompatible and resorbable), silicone rubber, and collagen. Overall, 146 patients were treated in the clinical studies. After surgery, many patients were completely pain-free or had considerable improvement in pain scores, whereas some patients did not have improvement or were not satisfied after the procedure. Nerve capping was used in 18 preclinical animal studies, using a variety of capping materials including autologous tissues, silicone, and synthetic nanofibers. Preclinical studies demonstrated successful reduction in rates of neuroma formation. CONCLUSIONS: Nerve capping has undergone major advancements since its beginnings and is now a useful option for the treatment or prevention of neuromas. As knowledge of peripheral nerve injuries and neuroma prevention grows, the criterion standard neuroprotective material for enhancement of nerve regeneration can be identified and applied to produce reliable surgical outcomes.

Retrograde peripheral nerve regeneration from sensory to motor pathways in rats: a new experimental concept in nerve repair.

BACKGROUND: The polarity of nerve grafts does not interfere with axon growth. Our goal was to investigate whether axons can regenerate in a retrograde fashion within sensory pathways and then extend into motor pathways, leading to muscle reinnervation. METHODS: Fifty-four rats were randomized into four groups. In Group 1, the ulnar nerve was connected end-to-end to the superficial radial nerve after neurectomy of the radial nerve in the axilla. In Group 2, the ulnar nerve was connected end-to-end to the radial nerve distal to the humerus; the radial nerve then was divided in the axilla. In Group 3, the radial nerve was divided in the axilla, but no nerve reconstruction was performed. In Group 4, the radial nerve was crushed in the axilla. Over 6 months, we behaviorally assessed the recovery of toe spread in the right operated-upon forepaw by lifting the rat by its tail and lowering it onto a flat surface. Six months after surgery, rats underwent reoperation, nerve transfers were tested electrophysiologically, and the posterior interosseous nerve (PIN) was removed for histological evaluation. RESULTS: Rats in the crush group recovered toe spread between 5 and 8 days after surgery. Rats with nerve transfers demonstrated electrophysiological and histological findings of nerve regeneration but no behavioral recovery. CONCLUSIONS: Ulnar nerve axons regrew into the superficial radial nerve and then into the PIN to reinnervate the extensor digitorum communis. We were unable to demonstrate behavioral recovery because rats cannot readapt to cross-nerve transfer.

Peripheral Nervous System Pain Modulation.

The percutaneous technique of electrode insertion in the vicinity of the greater occipital nerves to treat occipital neuralgia was first described in the 1990s by Weiner and Reed. This subsequently stimulated awareness of peripheral nerve stimulation (PNS). The more recent advent emergence of a minimally invasive percutaneous approach by way of using ultrasound has further increased the interest in PNS as a viable alternative to more invasive techniques. PNS has become more popular recently and is increasingly used to treat various pain conditions. Its foundation is fundamentally based on the gate control theory, although the precise mechanism underlying its analgesic effect is still indefinite. Studies have demonstrated the peripheral and central analgesic mechanisms of PNS by modulating the inflammatory pathways, the autonomic nervous system, the endogenous pain inhibition pathways, and the involvement of the cortical and subcortical areas. Peripheral nerve stimulation exhibits its neuromodulatory effect both peripherally and centrally. Further understanding of the modulation of PNS mechanisms can help guide stimulation approaches and parameters to optimize the use of PNS. his chapter aims to review the background and mechanisms of PNS modulation. PNS is becoming one of the most diverse therapies in neuromodulation due to rapid evolution and expansion. It is an attractive option for clinicians due to the simplicity and versatility of procedures that can be combined with other neuromodulation treatments or used alone. It has a distinct role in the modulation of functional conditions.

How to do an outside-in/outside-in microsuture for nerve repair.

Peripheral nerve injuries are common and debilitating. The goals of nerve repair are to accurately approximate the fascicular tissue, whilst ensuring continuous overlying epineurium and eliminating external sprouting of neural tissue. We describe a modification of standard micro-suturing which allows superior epineural eversion and fascicular coaptation.

The role of preoperative ultrasound in the management of peripheral nerve injuries.

BACKGROUND: Peripheral nerve injury refers to any damage or trauma to the nerves located outside the central nervous system. Ultrasonography is a reliable, cheap, and minimally invasive method in clinical practice to give physicians useful information about nerve injury. OBJECTIVES: to assess the power of ultrasound in determining the presence, localization, and extent of neural damage in patients with clinical evidence of peripheral nerve lesions before surgery. METHODS: This cross-sectional study was conducted on 78 patients (56 females and 22 males, aged from 9 to 52 years) who had different pathologies including entrapment, tumoral, post-traumatic, and post-surgical nerve injuries at the Neurosurgery and Physical Medicine, Rheumatology, and Rehabilitation Departments, Tanta University Hospitals. All studied patients had preoperative evaluation; neurological examination, electrodiagnostic studies, and sonographic examinations with linear array transducers (frequencies ranging from 7.5 to 16 MHz). RESULTS: The most common pathological condition was entrapment neuropathy (39 patients) (50%). Ultrasound complemented the electrodiagnostic studies by determining the site of entrapment manifested by increased mean maximum cross-sectional area of the nerve proximal to the site of entrapment and nerve hypoechogenicity. In post-traumatic and iatrogenic neuropathies (35 patients) (44.9%), the ultrasound finding revealed neuroma in continuity in nine cases (11.5%), complete neurotmesis with stump neuroma in eighteen patients (23.1%), and eight cases (10.3%) showed perineural adhesion. In all cases, the nerve was hypoechoic at the site of injury. The presence of hyperechoic fibrous tissue could indicate perineural adhesion and the necessity for neurolysis. This study also included three (3.8%) cases had schwannoma, and one case (1.3%) had neurofibroma. Ultrasound was used to confirm the diagnosis by determining the tumor's size and vascular supply. CONCLUSIONS: Ultrasonography is a diagnostic and surgical planning tool that is becoming more and more useful for the management of peripheral nerve injuries. Its high resolution and real-time capability provide safe and cost-effective scans that aid in determining the extent of injuries. For patients with peripheral nerve injuries, ultrasound is advised to be added to the routine clinical and neurophysiological evaluation. It is also advised to use ultrasound as a first-line imaging modality for tumors thought to be of nerve origin.

Superior Cluneal Nerve Entrapment Syndrome: Thought to Be Spondylolysis.

A rare but typically overlooked diagnosis in the orthopaedic surgery community is superior cluneal nerve (SCN) entrapment syndrome. The cluneal nerves function as purely sensory fibers, and the SCNs provide cutaneous innervation to the posterior parasacral, gluteal, and posterolateral thigh regions. When irritated, this syndrome can cause acute and chronic lower back pain and lower extremity symptoms. A 14-year-old adolescent girl presented to the clinic for an evaluation of pain in the right side of her lower back. The patient's physical examination showed tenderness to palpation on the right posterior iliac crest seven centimeters from the midline. Her neurologic examination demonstrated normal deep tendon reflexes, muscle strength, and sensation in the L2-S1 dermatomal distribution. Although imaging showed evidence of a left L5 spondylolysis, she responded positively to a steroid injection over the posterior iliac crest but negatively to one over the L5 pars defect. She later underwent a right SCN decompression surgery. After the procedure, she reported at least 90% improvement in her pain and rated it as a one in severity, on a scale of 0 to 10. Research regarding SCN entrapment syndrome has increased in the past several years. However, most of these studies are limited to the adult population. Therefore, more reports highlighting the potential for this syndrome in adolescents are needed as well.

[Choice of flaps for phalloplasty: what is the contemporary standard? Consensus Statement of the German-Speaking Society for Microsurgery of Peripheral Nerves and Vessels]. / "Wahl der Lappenplastik zur Phalloplastik ­ was ist zeitgemäßer Standard" ­ Konsensus-Bericht der deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie der peripheren Nerven und Gefäße.

The ever-expanding number of transmen as well as their surgeons share an increasing interest in the construction of a neophallus. While the indication for surgery and the positive effect of a phalloplasty on the quality of life, mental health and sexual function has already been thoroughly analysed, there is a lack of data comparing and evaluating the surgical steps. During the consensus conference on the "choice of flaps for phalloplasty" at the annual meeting of the German-Speaking Society for Microsurgery of Peripheral Nerves and Vessels, the current literature was discussed and a consensus on the surgical technique of a phalloplasty was reached. This manuscript publishes jointly developed recommendations on the following topics: choice of flaps for phalloplasty, preoperative diagnostic tests before phalloplasty, urethral construction in the radial forearm flap and anterior lateral thigh flap, preformation of the urethra at the forearm or thigh, venous drainage of the radial forearm flap, innervation of the phallus, staged phalloplasty, coronaplasty and managing the donor site of a radial forearm flap.

Google Trends Analysis of Peripheral Nerve Disease and Surgery.

BACKGROUND: Despite advances in the surgical management of peripheral nerve pathologies over the past several decades, it is unknown how public awareness of these procedures has changed. We hypothesize that Google searches for peripheral nerve surgery have increased over time. METHODS: Google Trends was queried for search volumes of a list of 40 keywords related to the following topics in peripheral nerve surgery: spasticity, nerve injury, prosthetics, and nerve pain. Monthly relative search volume over the first 5 years of the study period (2010-2014) was compared with that of the last 5 years (2018-2022) of the study period. RESULTS: Search volumes for keywords "nerve injury," "nerve laceration," "peripheral nerve injury," "nerve repair," "nerve transfer", "neuroma," "neuroma pain," "nerve pain," "nerve pain surgery," and "neuroma pain surgery" all increased more than 10% points in relative search volume over the study period (P < 0.0001 for each keyword). In contrast, searches for "rhizotomy," "spasticity surgery," "targeted muscle reinnervation," "bionic arm," and "myoelectric prosthesis" either decreased or remained stable. Technical terms such as "selective neurectomy," "hyperselective neurectomy," "regenerative peripheral nerve interface," and "regenerative peripheral nerve interface surgery" did not have adequate search volume to be reported by Google Trends. CONCLUSIONS: The increase in Google searches related to nerve injury and pain between 2010 and 2022 may reflect increasing public recognition of these clinical entities and surgical techniques addressing them. Technical terms relating to nerve pain are infrequently searched, surgeons should use plain English terms for online discovery. Interest in spasticity and myoelectric prosthetics remains stable, indicating an opportunity for better public outreach.

Multifunctional wet-adhesive chitosan/acrylic conduit for sutureless repair of peripheral nerve injuries.

The incidence of peripheral nerve injury (PNI) is high worldwide, and a poor prognosis is common. Surgical closure and repair of the affected area are crucial to ensure the effective treatment of peripheral nerve injuries. Despite being the standard treatment approach, reliance on sutures to seal the severed nerve ends introduces several limitations and restrictions. This technique is intricate and time-consuming, and the application of threading and punctate sutures may lead to tissue damage and heightened tension concentrations, thus increasing the risk of fixation failure and local inflammation. This study aimed to develop easily implantable chitosan-based peripheral nerve repair conduits that combine acrylic acid and cleavable N-hydroxysuccinimide to reduce nerve damage during repair. In ex vivo tissue adhesion tests, the conduit achieved maximal interfacial toughness of 705 J m-2 ± 30 J m-2, allowing continuous bridging of the severed nerve ends. Adhesive repair significantly reduces local inflammation caused by conventional sutures, and the positive charge of chitosan disrupts the bacterial cell wall and reduces implant-related infections. This promises to open new avenues for sutureless nerve repair and reliable medical implants.