Multichannel Conduits with Fascicular Complementation: Significance in Long Segmental Peripheral Nerve Injury.

Despite the advances in tissue engineering approaches, reconstruction of long segmental peripheral nerve defects remains unsatisfactory. Although autologous grafts with proper fascicular complementation have shown meaningful functional recovery according to the Medical Research Council Classification (MRCC), the lack of donor nerve for such larger defect sizes (>30 mm) has been a serious clinical issue. Further clinical use of hollow nerve conduits is limited to bridging smaller segmental defects of denuded nerve ends (<30 mm). Recently, bioinspired multichannel nerve guidance conduits (NGCs) gained attention as autograft substitutes as they mimic the fascicular connective tissue microarchitecture in promoting aligned axonal outgrowth with desirable innervation for complete sensory and motor function restoration. This review outlines the hierarchical organization of nerve bundles and their significance in the sensory and motor functions of peripheral nerves. This review also emphasizes the major challenges in addressing the longer nerve defects with the role of fascicular arrangement in the multichannel nerve guidance conduits and the need for fascicular matching to accomplish complete functional restoration, especially in treating long segmental nerve defects. Further, currently available fabrication strategies in developing multichannel nerve conduits and their inconsistency in existing preclinical outcomes captured in this review would seed a new process in designing an ideal larger nerve conduit for peripheral nerve repair.

Socioeconomic factors and outcome after repair and reconstruction of digital and major nerve trunk injuries in the upper limb.

Peripheral nerve injuries in the upper limb can lead to substantial disability and pain. We aimed to assess how socioeconomic factors affect outcomes after repaired or reconstructed digital or major nerve trunk injuries in the upper limb. We identified 670 individuals, who underwent surgical nerve repair or reconstruction using sensory nerve autografts, in the Swedish National Quality Registry for Hand Surgery 2010-2018. Socioeconomic factors, including education, cohabitation, type of work, sick leave, immigrant status and income, were gathered from the Swedish statistical agency ( www.scb.se ) and National Diabetes Register (NDR). We calculated prevalence ratios (PR) to assess the relationship between socioeconomic factors and surgical outcomes for the nerve injuries. Individuals with a major nerve trunk injury had higher QuickDASH scores and lower income compared to those with digital nerve injury. Individuals with immigration background (adjusted PR = 2.0, 95% CI 1.2-3.2), history of > 4 weeks of sick leave the year before surgery (adjusted PR = 1.8, 95% CI 1.1-3.1), or education level below tertiary (adjusted PR = 2.8, 95% CI 1.7-4.7) had significantly higher QuickDASH scores. Recognizing impact of non-biological factors, including immigration, prior sick leave, and education level, on outcome after nerve surgery is crucial for improving prognosis in socioeconomically deprived individuals.

A Systematic Review of Registered Clinical Trials for Peripheral Nerve Injuries.

ABSTRACT: Upper extremity peripheral nerve injuries (PNIs) significantly impact daily functionality and necessitate effective treatment strategies. Clinical trials play a crucial role in developing these strategies. However, challenges like retrospective data collection, reporting biases, inconsistent outcome measures, and inadequate data sharing practices hinder effective research and treatment advancements. This review aims to analyze the landscape of reporting, methodological design, outcome measures, and data sharing practices in registered clinical trials concerning upper extremity PNIs. It seeks to guide future research in this vital area by identifying current trends and gaps.A systematic search was conducted on ClinicalTrials.gov and WHO International Clinical Trials Registry Platform up to November 10, 2023, using a combination of MeSH terms and keywords related to upper extremity nerve injury. The PRISMA 2020 guidelines were followed, and the studies were selected based on predefined inclusion and exclusion criteria. A narrative synthesis of findings was performed, with statistical analysis for associations and completion rates.Of 3051 identified studies, 96 met the inclusion criteria. These included 47 randomized controlled trials, 27 nonrandomized trials, and others. Sensory objective measures were the most common primary outcomes. Only 13 studies had a data sharing plan. The analysis revealed varied intervention methods and inconsistencies in outcome measures. There was a significant association between study funding, design, and completion status, but no association between enrollment numbers and completion.This review highlights the need for standardized outcome measures, patient-centered assessments, and improved data sharing in upper extremity PNI trials. The varied nature of interventions and inconsistency in outcome measures indicate the necessity for more rigorous and transparent research practices to strengthen the evidence base for managing these injuries.

[Functional Outcome of Peripheral Nerve Injury after Pediatric Supracondylar Humerus Fracture: Comparison of Surgical and Conservative Treatment]. / Funktionelle Ergebnisse peripherer Nervenverletzungen nach kindlichen suprakondylären Humerusfrakturen: Vergleich operativer und konservativer Behandlung.

Supracondylar humerus fractures are the most common elbow fractures in children up to 10 years of age. The incidence of associated nerve injuries varies up to 15% depending on the data. Traumatic and iatrogenic lesions mainly affect the ulnar nerve. The regeneration of peripheral nerves is comparatively better in childhood. In the present study, the functional results after surgical and conservative treatment of nerve injuries in children after supracondylar fractures were compared and analyzed for influencing factors. In this retrospective comparative study, clinical data of pediatric nerve injuries following supracondylar humerus fractures treated over a period of 13 years (2008-2021) were analyzed. Children who were treated surgically (neurolysis, autologous reconstruction) due to insufficient clinical/neurophysiological improvement within 6 months after trauma or who were followed up conservatively in case of regression of symptoms within 6 months after trauma were included. All patients underwent multidisciplinary follow-up. 48 patients (26 female/22 male) with nerve injuries were included in this study. All patients had a history of surgical treatment with K- wire fixation due to severe dislocated fractures. The mean age was 7±2 years. The initial symptoms were severe motor deficits in all patients and sensory deficits in 87.5% (n=42). Isolated lesions of the ulnar nerve were most common (n=24, 50%). The nerve was neurolysed in 21 patients and additionally transferred to the volar side in 15. Nerve grafting was performed in 7 children and split repair in 2. Postoperatively, there was a significant improvement in motor function in all patients. Despite comparably severe motor deficits at initial presentation, further 20 children were treated conservatively due to the regression of neurological deficits. They showed comparably good functional results. No serious complications were recorded in either group. The average follow-up time was 377.25±524.87 days. The presented study shows excellent functional results after surgical treatment of pediatric nerve injuries without severe complications. Children with comparatively high-grade lesions at initial presentation have a good chance of complete spontaneous remission even without surgery. For this reason, the indication for surgery in children should be very carefully considered.

Risk of suprascapular nerve injury in open Trillat procedure: an anatomical study.

PURPOSE: The open Trillat Procedure described to treat recurrent shoulder instability, has a renewed interest with the advent of arthroscopy. The suprascapular nerve (SSN) is theoretically at risk during the drilling of the scapula near the spinoglenoid notch. The purpose of this study was to assess the relationship between the screw securing the coracoid transfer and the SSN during open Trillat Procedure and define a safe zone for the SSN. METHODS: In this anatomical study, an open Trillat Procedure was performed on ten shoulders specimens. The coracoid was fixed by a screw after partial osteotomy and antero-posterior drilling of the scapular neck. The SSN was dissected with identification of the screw. We measured the distances SSN-screw (distance 1) and SSN-glenoid rim (distance 2). In axial plane, we measured the angles between the glenoid plane and the screw (α angle) and between the glenoid plane and the SSN (ß angle). RESULTS: The mean distance SSN-screw was 8.8 mm +/-5.4 (0-15). Mean α angle was 11°+/-2.4 (8-15). Mean ß angle was 22°+/-6.7 (12-30). No macroscopic lesion of the SSN was recorded but in 20% (2 cases), the screw was in contact with the nerve. In both cases, the ß angle was measured at 12°. CONCLUSION: During the open Trillat Procedure, the SSN can be injured due to its anatomical location. Placement of the screw should be within 10° of the glenoid plane to minimize the risk of SSN injury and could require the use of a specific guide or arthroscopic-assisted surgery.

Beyond the limiting gap length: peripheral nerve regeneration through implantable nerve guidance conduits.

Peripheral nerve damage results in the loss of sensorimotor and autonomic functions, which is a significant burden to patients. Furthermore, nerve injuries greater than the limiting gap length require surgical repair. Although autografts are the preferred clinical choice, their usage is impeded by their limited availability, dimensional mismatch, and the sacrifice of another functional donor nerve. Accordingly, nerve guidance conduits, which are tubular scaffolds engineered to provide a biomimetic environment for nerve regeneration, have emerged as alternatives to autografts. Consequently, a few nerve guidance conduits have received clinical approval for the repair of short-mid nerve gaps but failed to regenerate limiting gap damage, which represents the bottleneck of this technology. Thus, it is still necessary to optimize the morphology and constituent materials of conduits. This review summarizes the recent advances in nerve conduit technology. Several manufacturing techniques and conduit designs are discussed, with emphasis on the structural improvement of simple hollow tubes, additive manufacturing techniques, and decellularized grafts. The main objective of this review is to provide a critical overview of nerve guidance conduit technology to support regeneration in long nerve defects, promote future developments, and speed up its clinical translation as a reliable alternative to autografts.

Does prophylactic decompression of distal nerves following nerve repair improve functional recovery? A systematic review.

BACKGROUND: Peripheral nerve injuries are burdensome on healthcare systems, individuals and society as a whole. The current standard of treatment for neurotmesis is primary neurorrhaphy or nerve grafting. However, several patients do not recover their full function. There has been a suggestion that primary distal neurolysis at common entrapment sites maximises surgical outcomes; however, no guidelines exist on this practice. This scoping review aims to ascertain the existing evidence on prophylactic distal decompression of peripheral nerves following repair. METHODS: A literature search was performed using Ovid Medline, PubMed, Embase and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews for studies published in the past 50 years. Studies were screened using a selection criteria and study quality was assessed using standardised tools. Furthermore, thematic content analysis was performed. RESULTS: Six studies were eligible for inclusion after screening; all studies were retrospective and at most level 3 evidence. No studies were designed specifically to assess the efficacy of distal neurolysis following proximal repair, thus no comparative data with control cohorts are available. All studies that recommended distal decompression of proximally repaired nerves based their conclusions on cases observed by the authors in practice or from theories on nerve regeneration. CONCLUSIONS: This systematic review suggests that the evidence on the role of immediate distal neurolysis in primary neurorrhaphy is inadequate. Recommendations are limited by the lack of large-scale and generalisable data. Further research is needed with definitive objective outcomes and patient-related outcome measures.

[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.

Anatomical considerations for nerve transfer in axillary nerve injury.

This study investigated the anatomical details of the axillary and radial nerves in 50 upper limbs from 29 adult formalin-embalmed cadavers, and ten fresh upper limbs. The focus was on understanding the course, division, and ramifications of these nerves to improve treatment of shoulder dysfunction caused by axillary nerve damage. The axillary nerve divided anteriorly and posteriorly before passing the quadrangular space in all specimens, with specific distances to the first ramifications. It was found that the deltoid muscle's clavicular and acromial parts were always innervated by the anterior division of the axillary nerve, whereas the spinous part was variably innervated. The longest and thickest branches of the radial nerve to the triceps muscles were identified, with no statistically significant differences in fiber numbers among triceps branches. The study concludes that nerve transfer to the anterior division of the axillary nerve can restore the deltoid muscle in about 86% of shoulders, and the teres minor muscle can be restored by nerve transfer to the posterior division. The medial head branch and long head branch of radial nerve were identified as the best donor options.

Trigeminal or peripheral nerve stimulation improves functional outcomes of nerve recovery in a rodent forelimb gap repair model.

BACKGROUND: The hypothesis of this study was that trigeminal nerve stimulation (TNS) or peripheral nerve stimulation (PNS) could improve functional outcomes of peripheral nerve injury in a rat forelimb model when compared to control rats not receiving electrical stimulation (ES). While PNS is known to improve outcomes after nerve surgery, the role of TNS has not been explored. METHODS: Lewis rats were trained to perform a reach and grasp task before receiving a 2 mm gap repair of the ulnar and median nerves and randomized into four treatment groups: (1) sham injury, (2) nerve injury with sham ES, (3) nerve injury with PNS, and (4) nerve injury with TNS. Functional motor (median pull force and percent success in motor task) and sensory metrics (forelimb paw withdrawal thresholds) were collected both pre-injury and throughout rehabilitation. Nerves stained using Gomori's trichrome were assessed quantitatively and qualitatively. RESULTS: The sham ES group did not recover their pre-injury baseline functional outcomes. In contrast, the TNS and PNS groups fully recovered following injury, with no difference in functional outcomes between the pre-injury baseline and the final week of rehabilitation (P > 0.05, all). Histomorphology results demonstrated no quantitative difference, but qualitative differences in architecture were evident. CONCLUSIONS: Electrical stimulation of the trigeminal nerve or the injured nerve improved the functional outcomes of nerve regeneration in rodents. Histomorphology results of nerves from the TNS group support the proposed central mechanisms. This is an important step in translating this therapy as an adjunct, non-invasive treatment for high, mixed nerve injuries in humans.

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.

Cost-effectiveness analysis of Avance® allograft for the treatment of peripheral nerve injuries in the USA.

Aim: Peripheral nerve injury (PNI) is a debilitating condition with significant associated morbidity, and which places a substantial socioeconomic burden on healthcare systems worldwide. Recently, allograft has emerged as a viable surgical alternative to autograft for the treatment of PNI. This study evaluated the cost effectiveness of allograft (Avance® Nerve Graft) compared with autograft for the peripheral nerve repair, from a US payer perspective. Methods: A Markov cohort model was developed to consider the treatment pathways followed by a patient population undergoing a single transected nerve repair with either allograft, or autograft. The marginal difference in meaningful recovery (MR) (effectiveness), and costs, between the two groups were estimated over a lifetime horizon. Deterministic and probabilistic sensitivity analyses (PSA) were performed to consider the uncertainty surrounding the base-case input parameter values and their effect on the overall incremental cost-effectiveness ratio (ICER). Results: The base-case analysis indicates that there is a small difference in the average probability of MR between the two groups (75.15% vs 70.46%; +4.69% with allograft). Allograft also results in cost savings ($12,677 vs $14,023; -$-1346 with allograft) compared with autograft. Deterministic sensitivity analysis shows that the costs of the initial surgical procedures are the main drivers of incremental cost, but that the intervention is likely to be cost saving compared with autograft regardless of the parameter variations made. Conclusion: The use of allograft with the Avance Nerve Graft has the potential to be a cost-effective alternative to autograft for the surgical treatment of PNI in the USA.

Can phrenic nerve injury be anticipated by larger cryoballoons?

Recently, a novel size-adjustable cryoballoon has been introduced in clinical practice, which can be inflated to two different diameters (28 and 31 mm). The 31 mm cryoballoon is specifically designed to achieve better contact with remodeled pulmonary veins (PVs) that have wider ostia while avoiding deep cannulation, thereby potentially reducing the risk of phrenic nerve injury (PNI) associated with deep balloon cannulation. However, we encountered two cases of PNI during cryoballoon ablation using the novel system among our initial 25 consecutive case series. Herein, we present two cases that exhibited PNI during freezing of the right superior PV with a size-adjustable balloon. While larger balloons are expected to create a larger area of isolation, the safety of this novel balloon system needs to be evaluated in a large-scale clinical study.

Key Considerations for Nerve Transfer Rehabilitation After Surgical Reconstruction for Brachial Plexus and Peripheral Nerve Injuries.

Nerve transfer surgery is commonly used to treat patients with brachial plexus injuries. However, guidelines on postoperative rehabilitation are not clearly established. Nerve transfers require the patient to relearn how to recruit newly innervated muscle(s), which may not occur naturally or intuitively. Supervised therapy is a valuable resource to guide patients through their lengthy recovery (often >12 months) because target muscle strength is both obtained and functionally used in daily life. This article highlights 10 key principles that provide the foundation for rehabilitation following nerve transfer surgery after a brachial plexus injury. Due to the shortcomings of the current evidence base for nerve transfer rehabilitation, we have included our anecdotal experience to augment the existing literature. It is important to have a collaborative surgeon-therapist relationship to communicate regarding operative details, expected timelines for reinnervation, patient needs, and realistic expectations. We provide examples of how to tailor the exercise program to synergistically recruit both the donor and target muscle action, including how to appropriately advance exercises based on the current level of nerve return. We also discuss the role that fatigue plays in denervated muscle and how fatigue may affect the exercise demands placed on the target muscle during specific stages of recovery.

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.

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.

Novel Bioinspired Nerve Scaffold with High Synchrony between Biodegradation and Nerve Regeneration for Repair of Peripheral Nerve Injury.

The morphological structure reconstruction and functional recovery of long-distance peripheral nerve injury (PNI) are global medical challenges. Biodegradable nerve scaffolds that provide mechanical support for the growth and extension of neurites are a desired way to repair long-distance PNI. However, the synchrony of scaffold degradation and nerve regeneration is still challenging. Here, a novel bioinspired multichannel nerve guide conduit (MNGC) with topographical cues based on silk fibroin and ε-polylysine modification was constructed. This conduit (SF(A) + PLL MNGC) exhibited sufficient mechanical strength, excellent degradability, and favorable promotion of cell growth. Peripheral nerve repairing was evaluated by an in vivo 10 mm rat sciatic model. In vivo evidence demonstrated that SF(A) + PLL MNGC was completely biodegraded in the body within 4 weeks after providing sufficient physical support and guide for neurite extension, and a 10 mm sciatic nerve defect was effectively repaired without scar formation, indicating a high synchronous effect of scaffold biodegradation and nerve regeneration. More importantly, the regenerated nerve of the SF(A) + PLL MNGC group showed comparable morphological reconstruction and functional recovery to that of autologous nerve transplantation. This work proved that the designed SF(A) + PLL MNGC has potential for application in long-distance PNI repair in the clinic.