Nerve Allografts: Current Utility and Future Directions.

Processed nerve allograft is a widely accepted tool for reconstructing peripheral nerve defects. Repair parameters that need to be considered include gap length, nerve diameter, nerve type (motor, sensory, or mixed), and the soft tissue envelope. Although the use of processed nerve allograft must be considered based on each unique clinical scenario, a rough algorithm can be formed based on the available animal and clinical literature. This article critically reviews the current surgical algorithm, defines the role of processed nerve allograft compared with nerve autograft, and discusses how this role may change in the future.

Alternative Nerve Coaptations: End-To-Side and Beyond.

Modern end-to-side (ETS) nerve transfers have undergone several permutations since the early 1990's. Preclinical data have revealed important mechanisms and patterns of donor axon outgrowth into the recipient nerves and target reinnervation. The versatility of ETS nerve transfers can also potentially address several processes that limit functional recovery after nerve injury by babysitting motor end-plates and/or supporting the regenerative environment within the denervated nerve. Further clinical and basic science work is required to clarify the ideal clinical indications, contraindications, and mechanisms of action for these techniques in order to maximize their potential as reconstructive options.

Therapeutic Electrical Stimulation for Surgeons: How it Works and How to Apply it.

Electrical stimulation (ES) enhances peripheral nerve inherent regeneration capacity by promoting accelerated axonal outgrowth and selectivity toward appropriate motor and sensory targets. These effects lead to significantly improved functional outcomes and shorter recovery time. Electrical stimulation can be applied intra-operatively or immediately post-operatively. Active clinical trials are looking into additional areas of application, length of stimulation, and functional outcomes.

Is RATS Superior to VATS in Thoracic Autonomic Nervous System Surgery?

Technological development in the field of robotics has meant that, in recent years, more and more thoracic surgery departments have adopted this type of approach at the expense of VATS, and today robotic surgery boasts numerous applications in malignant and benign thoracic pathology. Because autonomic nervous system surgery is a high-precision surgery, it is conceivable that the application of RATS could lead to improved outcomes and reduced side effects, but its feasibility has not yet been thoroughly studied. This review identified three main areas of application: (1) standard thoracic sympathectomy, (2) selective procedures, and (3) nerve reconstruction. Regarding standard sympathectomy and its usual areas of application, such as the management of hyperhidrosis and some cardiac and vascular conditions, the use of RATS is almost anecdotal. Instead, its impact can be decisive if we consider selective techniques such as ramicotomy, optimizing selective surgery of the communicating gray branches, which appears to reduce the incidence of compensatory sweating only when performed with the utmost care. Regarding sympathetic nerve reconstruction, there are several studies, although not conclusive, that point to it as a possible solution to reverse surgical nerve interruption. In conclusion, the characteristics of RATS might make it preferable to other techniques and, particularly, VATS, but to date, the data in the literature are too weak to draw any evidence.

Current perspectives on peripheral nerve repair and management of the nerve gap.

From the first surgical repair of a nerve in the 6th century, progress in the field of peripheral nerve surgery has marched on; at first slowly but today at great pace. Whether performing primary neurorrhaphy or managing multiple large nerve defects, the modern nerve surgeon has an extensive range of tools, techniques and choices available to them. Continuous innovation in surgical equipment and technique has enabled the maturation of autografting as a gold standard for reconstruction and welcomed the era of nerve transfer techniques all while bioengineers have continued to add to our armamentarium with implantable devices, such as conduits and acellular allografts. We provide the reader a concise and up-to-date summary of the techniques available to them, and the evidence base for their use when managing nerve transection including current use and applicability of nerve transfer procedures.

The 2-by-2 Inch "Key Window" in the Upper Extremity: An Anatomical Appraisal of the Accessibility and Proximity of the Major Nerves and Vessels.

BACKGROUND: The brachial plexus is a network of nerves located between the neck and axilla, which receives input from C5-T1. Distally, the nerves and blood vessels that supply the arm and forearm form a medial neurovascular bundle. The purpose of this study was to illustrate that a peripheral nerve dissection via a 2 × 2 inch window would allow for identification and isolation of the major nerves and blood vessels that supply the arm and forearm. METHODS: A right side formalin-fixed latex-injected cadaveric arm was transected at the proximal part of the axillary fold and included the scapular attachments. Step-by-step anatomical dissection was carried out and documented with three-dimensional digital imaging. RESULTS: A 2 × 2 inch window centered 2 inches distal to the axillary fold on the medial surface of the arm enabled access to the major neurovascular structures of the arm and forearm: the median nerve, ulnar nerve, medial antebrachial cutaneous nerve, radial nerve and triceps motor branches, musculocutaneous nerve and its biceps and brachialis branches and lateral antebrachial cutaneous nerve, basilic vein and brachial artery and vein, and profunda brachii artery. CONCLUSIONS: Our study demonstrates that the majority of the neurovascular supply in the arm and forearm can be accessed through a 2 × 2 inch area in the medial arm. Although this "key window" may not be entirely utilized in the operative setting, our comprehensive didactic description of peripheral nerve dissection in the cadaver laboratory can help in safer identification of complex anatomy encountered during surgical procedures.

"Toward Breast Reinnervation- What is our Endpoint" A systematic review of normal breast sensibility.

BACKGROUND: To restore breast sensibility, some centers are offering nerve reconstruction as a component of implant and flap-based breast reconstruction. To interpret and contextualize the results of these procedures, it is necessary to understand the normal range of breast sensibility, the factors that affect it, and the best methods for its objective measurement. METHODS: We conducted systematic and comprehensive searches across PubMed, Web of Science, and Cochrane Library databases using keywords and controlled vocabulary for the concepts of the breast, nipple, areola, and measurement. The search results were imported into Rayyan QCRI for a blinded screening of titles and abstracts. Studies were evaluated for bias using RevMan 5 software. The results of sensory measurements were pooled, and a quantitative summary of breast sensibility was generated. RESULTS: A total of 36 articles were identified, including retrospective, cross-sectional, and prospective studies. Although there were some consistent findings across studies, such that breast sensibility is inversely related to breast volume, there was wide variability in the following parameters: population, breast condition, measurement modality, anatomic areas of measurement, and sensibility findings. This heterogeneity precluded the generation of normative breast sensibility measurements. Furthermore, we detected a high degree of bias in most studies, due to self-selection of participants and failure to record patient characteristics that may alter sensibility. CONCLUSIONS: The literature lacks consistent data delineating normative values for breast sensibility. Standardized measurements of healthy volunteers with various breast characteristics are necessary to elucidate normative values and interpret efforts to restore sensibility in breast reconstruction.

Retro Oesophageal Transfer of Contralateral C7 in Birth Brachial Plexus Injury - A Retrospective Study.

Background: Presence of available healthy nerve roots on the injured side determines the outcome after nerve reconstruction. Paucity of nerve roots warrants contralateral C7 harvest for optimal results. We aim to study the risks and benefits of retro oesophageal transfer of contralateral C7 root in infants with birth brachial plexus injury. Methods: Study was carried out from 2017 to 2022 in 13 children who have undergone retro oesophageal transfer of contralateral C7 root to affected side. Follow-up period ranged from 8 to 60 months after the surgery. Motor power assessment was done using by active movement scale. Results: Average active movement score for abduction was found to be 6, elbow flexion 5.7, elbow extension 5.8, wrist extension 3, wrist flexion 4, finger flexion 4.8 and finger extension 3.8, respectively. No neurological deficits, limb length anomaly noted in the normal upper limb after contralateral C7 harvest. Conclusions: Retro oesophageal transfer of contralateral C7 is a safe technique in birth brachial plexus injury. The advantage of retro oesophageal transfer is reduction in the length of nerve grafts, thus helping in early neurotisation of distal forearm and hand muscles. The large axonal output from contralateral C7 can be used to reconstruct different nerves without any residual deficits on the normal side. Level of Evidence: Level IV (Therapeutic).

Brachial plexus birth injury: advances and controversies.

While there is considerable spontaneous recovery in most cases of brachial plexus birth injury, many children are left with significant problems that may lead to lifelong functional limitations, loss of work and social isolation. Detailed treatment with the right strategy can provide very valuable improvement in function. Over the past few years, the clinical approach to brachial plexus birth palsy has entered a new era in both diagnostic and surgical treatment methods. This article reviews four areas of management, the role of imaging in defining the severity of the injury, the optimal timing of for nerve exploration and reconstruction in appropriate cases, the advantages and potential complications of nerve transfers, and the role of physiotherapy. Available evidence is considered. Although it is difficult to make clear and precise inferences on a subject where there are many variables and considerable uncertainties, some currently accepted views will be summarized.Level of evidence: V.

Comparison of nerve versus tendon transfer for radial nerve palsy.

OBJECTIVE: This study aims to investigate the choice of intervention time and operation mode between nerve and tendon transfer for the treatment of radial nerve palsy (RNP). METHODS: 46 RNP patients underwent nerve transfer (n = 22) and tendon transfer (n = 24). The intraoperative blood loss, main incision length, operation duration, and length of hospital stay and follow-up period of patients in these two groups were recorded and compared. The range of motion (ROM) of the elbow, wrist, fingers, and thumb, the hand grip and pinch strength, the Disabilities of Arm, Shoulder, and Hand (DASH) and the 36-Item Short Form Health Survey (SF-36) scores were measured and compared preoperatively and postoperatively between the two groups. RESULTS: The ROM of thumb and the hand grip strength of patients in the nerve transfer group were greater than that in the tendon transfer (P < 0.05). Both of the two groups indicated significant improvements in the ROM of elbow, wrist, finger, thumb and the hand grip and pinch strength (P < 0.05) postoperatively. The DASH scores decreased significantly at 6 months (P < 0.05) and 12 months (P < 0.05) after surgery in both groups, while the postoperative SF-36 scores significantly increased (P < 0.05). There was no significant difference in postoperative DASH and SF-36 scores between the two groups (P > 0.05). CONCLUSION: In summary, both nerve and tendon transfer techniques are effective treatments for RNP. Nerve transfer is particularly advantageous for early RNP, while tendon transfer is suitable for patients with radial nerve injury more than one year.

Surgery for patients with facial palsy in Germany: a diagnosis-related-groups-based nationwide analysis, 2005-2019.

PURPOSE: Chronic flaccid paralysis of the facial nerve leads to permanent dysfunction of eye closure, problems with drinking and eating, and lack of emotional expression. Modern facial surgery can help those affected. An analysis of the development of facial surgery in Germany over time is presented. METHODS: Nation-wide population-baes diagnosis-related case group (DRG) data of virtually all inpatients who underwent facial surgery for facial palsy between 2005 and 2019 were included. Binomial regression models for changes in surgery rates over time were calculated in relation to gender and treating specialty. RESULTS: Between 2005 and 2019, there were 28,622 inpatient stays for facial surgery. Most surgeries were provided by otolaryngology (39%) and ophthalmology or dentistry, oral and maxillofacial surgery (20% each). The mean treatment rate was 2.33 ± 0.53 surgeries per 100,000 person-years. The surgery rate was highest for nerve reconstruction surgery (0.46 ± 0.15) and static sling surgery (0.44 ± 0.0.16). The greatest increase was seen in men for nerve surgery (3.9-fold; relative risk [RR] = 3.68; confidence interval [CI] = 3.18-4.26) and sling surgery (5.0-fold; RR = 4.25; CI = 3.38-5.33). CONCLUSIONS: While nerve and sling surgery increased significantly over time, this was less true or not true at all for surgical techniques. Surgical rates and their change over time were greater in men, without explanation from the data.

Improving outcomes in traumatic peripheral nerve injuries to the upper extremity.

Peripheral nerve lesions of the upper extremity are common and are associated with devastating limitations for the patient. Rapid and accurate diagnosis of the lesion by electroneurography, neurosonography, or even MR neurography is important for treatment planning. There are different therapeutic approaches, which may show individual differences depending on the injured nerve. If a primary nerve repair is not possible, several strategies exist to bridge the gap. These may include autologous nerve grafts, bioartificial nerve conduits, or acellular nerve allografts. Tendon and nerve transfers are also of major importance in the treatment of nerve lesions in particular with long regeneration distances. As a secondary reconstruction, in addition to tendon transfers, there is also the option for free functional muscle transfer. In amputations, the prevention of neuroma is of great importance, for which different strategies exist, such as target muscle reinnervation, regenerative peripheral nerve interface, or neurotized flaps. In this article, we give an overview of the latest methods for the therapy of peripheral nerve lesions.

The Dynamics of Nerve Degeneration and Regeneration in a Healthy Milieu and in Diabetes.

Appropriate animal models, mimicking conditions of both health and disease, are needed to understand not only the biology and the physiology of neurons and other cells under normal conditions but also under stress conditions, like nerve injuries and neuropathy. In such conditions, understanding how genes and different factors are activated through the well-orchestrated programs in neurons and other related cells is crucial. Knowledge about key players associated with nerve regeneration intended for axonal outgrowth, migration of Schwann cells with respect to suitable substrates, invasion of macrophages, appropriate conditioning of extracellular matrix, activation of fibroblasts, formation of endothelial cells and blood vessels, and activation of other players in healthy and diabetic conditions is relevant. Appropriate physical and chemical attractions and repulsions are needed for an optimal and directed regeneration and are investigated in various nerve injury and repair/reconstruction models using healthy and diabetic rat models with relevant blood glucose levels. Understanding dynamic processes constantly occurring in neuropathies, like diabetic neuropathy, with concomitant degeneration and regeneration, requires advanced technology and bioinformatics for an integrated view of the behavior of different cell types based on genomics, transcriptomics, proteomics, and imaging at different visualization levels. Single-cell-transcriptional profile analysis of different cells may reveal any heterogeneity among key players in peripheral nerves in health and disease.

Advantages of simultaneous radial nerve and tendon reconstruction - a case report.

Transection of the radial nerve is frequently associated with humeral shaft fractures that are part of a very complex upper extremity injury. In the presented case, a 19-year-old man with a 10-cm radial nerve defect with a need for nerve grafting to recover complete sensory and motor deficit of the radial nerve. In our case, at the same time we provided the tendon transfer of musculus (m.) pronator teres to m. extensor carpi radialis brevis, m. flexor carpi ulnaris to m. extensor digitorum communis, m. palmaris longus to m. extensor pollicis longus, and long sural nerve graft because of an extensive zone of the injury. The assumption was that if these two procedures are performed in one surgery, it will accelerate overall recovery, restore the functionality of the upper limb more quickly, and thus enable a faster recovery.

Treatment options for digital nerve injury: a systematic review and meta-analysis.

BACKGROUND: Surgical treatment of finger nerve injury is common for hand trauma. However, there are various surgical options with different functional outcomes. The aims of this study are to compare the outcomes of various finger nerve surgeries and to identify factors associated with the postsurgical outcomes via a systematic review and meta-analysis. METHODS: The literature related to digital nerve repairs were retrieved comprehensively by searching the online databases of PubMed from January 1, 1965, to August 31, 2021. Data extraction, assessment of bias risk and the quality evaluation were then performed. Meta-analysis was performed using the postoperative static 2-point discrimination (S2PD) value, moving 2-point discrimination (M2PD) value, and Semmes-Weinstein monofilament testing (SWMF) good rate, modified Highet classification of nerve recovery good rate. Statistical analysis was performed using the R (V.3.6.3) software. The random effects model was used for the analysis. A systematic review was also performed on the other influencing factors especially the type of injury and postoperative complications of digital nerve repair. RESULTS: Sixty-six studies with 2446 cases were included in this study. The polyglycolic acid conduit group has the best S2PD value (6.71 mm), while the neurorrhaphy group has the best M2PD value (4.91 mm). End-to-side coaptation has the highest modified Highet's scoring (98%), and autologous nerve graft has the highest SWMF (91%). Age, the size of the gap, and the type of injury were factors that may affect recovery. The type of injury has an impact on the postoperative outcome of neurorrhaphy. Complications reported in the studies were mainly neuroma, cold sensitivity, paresthesia, postoperative infection, and pain. CONCLUSION: Our study demonstrated that the results of surgical treatment of digital nerve injury are generally satisfactory; however, no nerve repair method has absolute advantages. When choosing a surgical approach to repair finger nerve injury, we must comprehensively consider various factors, especially the gap size of the nerve defect, and postoperative complications. Type of study/level of evidence Therapeutic IV.

Mechanisms, interventions at risk and clinical presentation of iatrogenic nerve lesions in trauma patients.

BACKGROUND: Iatrogenic nerve lesions during surgical interventions are avoidable complications that may cause severe functional impairment. Hereby, awareness of physicians and knowledge of structures and interventions at risk is of utmost importance for prevention. As current literature is scarce, we evaluated all patients treated surgically due to peripheral nerve injuries in our specialized nerve center for the presence of iatrogenic nerve lesions. METHODS: We evaluated a total of 5026 patients with peripheral nerve injuries treated over a time period of 8 years in our facility for the prevalence of iatrogenic nerve injuries, their clinical presentations, time to treatment, mechanisms and intraoperative findings on nerve continuity. RESULTS: A total of 360 (6.1%) patients had an iatrogenic cause resulting in 380 injured nerves. 76.6% of these lesions affected the main branch of the injured nerve, which were mainly the radial (30.5%), peroneal (13.7%) and median nerve (10.3%). After a mean delay of 237 ± 344 days, patients presented 23.2% with a motor and 27.9% with a mixed sensory and motor deficit. 72.6% of lesions were in-continuity lesions. Main interventions at risk are displayed for every nerve, frequently concerning osteosyntheses but also patient positioning and anesthesiologic interventions. DISCUSSION: Awareness of major surgical complications such as iatrogenic nerve injuries is important for surgeons. An often-seen trivialization or "watch and wait" strategy results in a huge delay for starting an adequate therapy. The high number of in-continuity lesions mainly in close proximity to osteosyntheses makes diagnosis and treatment planning a delicate challenge, especially due to the varying clinical presentations we found. Diagnostics and therapy should therefore be performed as early as possible in specialized centers capable of performing nerve repair as well as salvage therapies.

Analysis of the Outcomes of Immediate Recurrent Laryngeal Nerve Reconstruction During Thyroid Surgery for Prevention of Vocal Fold Paralysis.

BACKGROUND: Recurrent laryngeal nerve (RLN) injury and the resulting paralysis is the most common and known complication of thyroid surgery. Several surgical techniques, such as medialization thyroplasty with or without arytenoid adduction and injection laryngoplasty, have been developed to treat RLN injury, but these procedures have specific limitations and complications. In this study, we present the outcomes for our patients who underwent immediate RLN reconstruction during thyroid surgery by analyzing both subjective and objective outcomes. METHODS: A retrospective study was conducted for patients who underwent total or subtotal thyroidectomy between May 2012 and March 2020. Among them, patients who underwent immediate RLN reconstruction due to unilateral RLN injury were followed for at least 12 months. The voice perceptual evaluation, acoustic analysis, voice range profile, and Voice Handicap Index (VHI) scores were obtained preoperatively, 1 month, 6 months, and 12 months after surgery. RESULTS: Among the 11 patients, 6 patients (54.5%) underwent direct anastomosis, and 5 patients (45.5%) underwent nerve grafts using ansa cervicalis and great auricular nerve. The grade and breathiness in the GRBAS (grade, roughness, breathiness, asthenia, and strain) scale and jitter item showed significant improvement at 12 months postoperatively, and although not statistically significant, the rest of the items also tended to improve. The total, functional, and physical scores on VHI improved significantly at 12 months postoperatively. Moreover, when comparing the voice analysis of the direct anastomosis group and the nerve graft group, there was no significant difference between the groups in objective and subjective results. CONCLUSION: Immediate RLN reconstruction demonstrated significant voice improvement postoperatively, and reconstructing the nerve immediately and combining follow-up treatment in the event of RLN injury will greatly help patients improve their long-term voice outcomes.

End-to-Side vs. Free Graft Nerve Reconstruction-Experimental Study on Rats.

The long history of regeneration nerve research indicates many clinical problems with surgical reconstruction to be resolved. One of the promising surgical techniques in specific clinical conditions is end-to-side neurorrhaphy (ETS), described and then repeated with different efficiency in the 1990s of the twentieth century. There are no reliable data on the quality of recipient nerve regeneration, possible donor nerve damage, and epineural window technique necessary to be performed. This research attempts to evaluate the possible regeneration after end-to-side neurorrhaphy, its quality, potential donor nerve damage, and the influence of epineural windows on regeneration efficiency. Forty-five female Wistar rats were divided into three equal groups, and various surgical technics were applied: A-ETS without epineural window, B-ETS with epineural window, and C-free graft reconstruction. The right peroneal nerve was operated on, and the tibial nerve was selected as a donor. After 24 weeks, the regeneration was evaluated by (1) footprint analysis every two weeks with PFI (peroneal nerve function index), TFI (tibial nerve function index), and SFI (sciatic nerve function index) calculations; (2) the amplitude and latency measurements of motor evoked potentials parameters recorded on both sides of the peroneal and tibial nerves when electroneurography with direct sciatic nerve electrical stimulation and indirect magnetic stimulation were applied; (3) histomorphometry with digital conversion of a transverse semithin nerve section, with axon count, fibers diameter, and calculation of axon area with a semiautomated method were performed. There was no statistically significant difference between the groups investigated in all the parameters. The functional indexes stabilized after eight weeks (PFI) and six weeks (TFI and SFI) and were positively time related. The lower amplitude of tibial nerve potential in groups A and B was proven compared to the non-operated side. Neurophysiological parameters of the peroneal nerve did not differ significantly. Histomorphometry revealed significantly lower diameter and area of axons in operated peroneal nerves compared to non-operated nerves. The axon count was at a normal level in every group. Tibial nerve parameters did not differ from non-operated values. Regeneration of the peroneal nerve after ETS was ascertained to be at the same level as in the case of free graft reconstruction. Peroneal nerves after ETS and free graft reconstruction were ascertained to have a lower diameter and area than non-operated ones. The technique of an epineural window does not influence the regeneration result of the peroneal nerve. The tibial nerve motor evoked potentials were characterized by lower amplitudes in ETS groups, which could indicate axonal impairment.

Challenges in Nerve Repair and Reconstruction.

Peripheral nerve injuries may substantially impair a patient's function and quality of life. Despite appropriate treatment, outcomes often remain poor. Direct repair remains the standard of care when repair is possible without excessive tension. For larger nerve defects, nerve autografting is the gold standard. However, a considerable challenge is donor site morbidity. Processed nerve allografts and conduits are other options, but evidence supporting their use is limited to smaller nerves and shorter gaps. Nerve transfer is another technique that has seen increasing popularity. The future of care may include novel biologics and pharmacologic therapy to enhance regeneration.