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Peripheral nerve injuries associated with reverse total shoulder arthroplasty (rTSA) are rarely reported and are often dismissed as neuropraxias, particularly in the setting of perioperative nerve blocks. The purpose of this study was to evaluate nerve injuries following rTSA to determine if there is a pattern of injury and to evaluate outcomes of patients who sustain an intraoperative nerve injury.A retrospective review was performed identifying patients who underwent rTSA and had a concomitant major nerve injury who were referred to a multidisciplinary peripheral nerve injury clinic. Demographic data, preoperative nerve block use, physical examination, electrodiagnostic studies, injury pattern, and time from injury to referral was collected. Radiographs, Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) score, and outcomes surveys were obtained at final follow-up.Twenty-two patients were identified with postoperative nerve injuries. Average time from injury to referral was 9.0 months, with 18.8 months' follow-up. Eight patients had undergone prior shoulder surgery, and 11 patients had prior shoulder trauma. Injury patterns were variable and involved diffuse pan-plexopathies with severity localized to the posterior and medial cords (11), the upper trunk (5), lateral cord (2), and axillary nerve (4). The average postoperative acromiohumeral distance (AHD) was 3.7 cm, with an average change of 2.9 cm. The average postoperative lateral humeral offset (LHO) was 1.1 cm, with an average change of 0.2 cm. Seventeen patients were confirmed to have undergone preoperative nerve blocks, which were initially attributed as the etiology of nerve injury. Eighteen patients were initially treated with observation: 11 experienced residual debilitating neuropathic pain and/or disability, and 7 had substantial improvement. One patient underwent nerve transfers, whereas the others underwent procedures for hand dysfunction improvement. The average QuickDASH score was 53.5 at average of 4 years post rTSA.Although uncommon, permanent peripheral nerve injuries following rTSA do occur with debilitating effects. Preoperative regional blocks were used in most cases, but none of the blocks could be directly attributed to the nerve injuries. Nerve injuries were likely secondary to traction at the time of arthroplasty and/or substantial distalization and lateralization of the implants. Patients with medial cord injuries had the most debilitating loss of hand function. Surgeons should be cognizant of these injuries and make a timely referral to a peripheral nerve specialist.

Peripheral nerve injuries of the upper limb are rare in children and poorly documented. The aim of this retrospective study was to analyze long-term sensory and motor results, and to determine predictive factors for recovery after surgery. Eleven children, with a mean age at injury of 9.7 years (5-15), operated on between 2006 and 2018, were included. Sensory perception was measured on monofilament test and static 2-point discrimination test. Grip strength was measured with a dynamometer and motor strength was assessed on the Medical Research Council scale. Quality of life was assessed on QuickDASH. The injury involved the radial (n = 1), median (n = 9), or combined median and ulnar (n = 1) nerves and was repaired by primary direct suture (n = 11). The mechanism involved glass laceration (n = 10) or a road accident (n = 1). The dominant limb was involved in 7 cases. At a mean 7.7 years' follow-up, touch sensitivity was normal or slightly deficient on monofilament test. Discrimination test was normal or adequate. Strength was complete in 10 patients. Mean QuickDASH score was 5.99 (range, 0-18.18). There was no significant difference in sensory or motor recovery according to partial or complete lesion or to injury location. There was better sensory recovery in children12 years (p 0.05). Sensory prognosis was also better in the absence of associated lesions (p 0.05). Sensory, motor and functional results after surgical treatment of peripheral nerve injuries of the upper limb in children were globally satisfactory. Sensory recovery was better at an early age and in the absence of associated lesions. LEVEL OF EVIDENCE: IV.

In this article, the authors review the incidence and causes of iatrogenic peripheral nerve injuries following shoulder arthroplasty and provide preventative measures to decrease nerve injury rate and management options. They describe common direct and indirect causes of injury such as laceration and retractor use versus arm positioning and lengthening, respectively. Preventative measures include an understanding of anatomy and high-risk locations in the shoulder, minimizing extreme ranges of arm motion and utilization of intraoperative nerve monitoring. Lastly, the authors review diagnosis and management of neurologic symptoms including how and when to use electrodiagnostic studies, nerve grafts, transfers, or muscle/tendon transfers.

Peripheral nerve injuries in the upper extremities may be common in throwing athletes as the throwing motion places extreme stress on the dominant arm. The combination of extreme stress along with repetitive microtrauma from throwing uniquely places the throwing athlete at elevated risk of upper extremity peripheral nerve injury. However, because symptoms can be nonspecific and frequently coexist with pathology in the upper extremity, the diagnosis of peripheral nerve injury is often delayed. Diagnosis of peripheral nerve injuries may require a combination of history and physical examination, diagnostic imaging, electrodiagnostic testing, and diagnostic ultrasound-guided injections. The primary management should include physical therapy focusing on throwing mechanics and kinetic chain evaluation. However, some athletes require surgical intervention if symptoms do not improve with conservative management. The purpose of this focused narrative review is to highlight upper extremity peripheral neuropathies reported in throwing athletes and to provide an overview of the appropriate clinical diagnosis and management of the throwing athlete with a peripheral nerve injury.

OBJECTIVE Schwann cells (SCs) have been shown to play an essential role in axon regeneration in both peripheral nerve injuries (PNIs) and spinal cord injuries (SCIs). The transplantation of SCs as an adjunctive therapy is currently under investigation in human clinical trials due to their regenerative capacity. Therefore, a reliable method for procuring large quantities of SCs from peripheral nerves is necessary. This paper presents a well-developed, validated, and optimized manufacturing protocol for clinical-grade SCs that are compliant with Current Good Manufacturing Practices (CGMPs). METHODS The authors evaluated the SC culture manufacturing data from 18 clinical trial participants who were recruited for autologous SC transplantation due to subacute SCI (n = 7), chronic SCI (n = 8), or PNIs (n = 3). To initiate autologous SC cultures, a mean nerve length of 11.8 ± 3.7 cm was harvested either from the sural nerve alone (n = 17) or with the sciatic nerve (n = 1). The nerves were digested with enzymes and SCs were isolated and further expanded in multiple passages to meet the dose requirements for transplantation. RESULTS An average yield of 87.2 ± 89.2 million cells at P2 and 150.9 ± 129.9 million cells at P3 with high viability and purity was produced. Cell counts and rates of expansion increased with each subsequent passage from P0 to P3, with the largest rate of expansion between P2 and P3. Larger harvest nerve lengths correlated significantly with greater yields at P0 and P1 (p < 0.05). In addition, a viability and purity above 90% was sustained throughout all passages in nearly all cell products. CONCLUSIONS This study presents reliable CGMP-compliant manufacturing methods for autologous SC products that are suitable for regenerative treatment of patients with SCI, PNI, or other conditions.

To review advances in the diagnostic evaluation and management of traumatic peripheral nerve injuries.Serial multimodal assessment of peripheral nerve injuries facilitates assessment of spontaneous axonal regeneration and selection of appropriate patients for early surgical intervention. Novel surgical and rehabilitative approaches have been developed to complement established strategies, particularly in the area of nerve grafting, targeted rehabilitation strategies and interventions to promote nerve regeneration. However, several management challenges remain, including incomplete reinnervation, traumatic neuroma development, maladaptive central remodeling and management of fatigue, which compromise functional recovery.Innovative approaches to the assessment and treatment of peripheral nerve injuries hold promise in improving the degree of functional recovery; however, this remains a complex and evolving area.

Neuropathies are commonplace in clinical practice and ultrasound assessment of the peripheral nerves is increasingly becoming a valuable diagnostic tool to support the physical and electrophysiological examinations. In the pertinent literature, several sonographic approaches have been proposed to evaluate the peripheral nerve tissue-mainly based on (semi)-quantitative measures.To define a standardized sonographic approach aiming to evaluate the different sono-histological sections of the peripheral nerve also in a qualitative way.Using high-frequency ultrasound probes and high-level ultrasound machines, we matched the histopathological features of the peripheral nerve (in acute and chronic phase) and the different sonographic patterns. Moreover, high-sensitive power Doppler assessments have been performed to assess the microcirculation of the peripheral nerve in physiological and pathological conditions.Modern ultrasound equipment allows a "real-time dissection" of the peripheral nerve evaluating the sonographic patterns of its different histological compartments in physiological and pathological conditions. Moreover, high-sensitive power Doppler allows clear visualization of the microcirculation of the peripheral nerve both in the acute and chronic phases of the neuropathy.In clinical practice, using adequate technological equipment, (semi)-quantitative measurements of the peripheral nerve can be coupled with different sonographic patterns of its histological components-both in the acute and chronic phase of the peripheral neuropathy. This way, better/prompt diagnosis and optimal management of the patients would be possible.

Background Iatrogenic nerve injuries can result from surgical damage. Thus, physicians should be aware of the risk factors and procedures that need to be followed in such patients. The purpose of this study was to examine data pertaining to patients with known iatrogenic nerve injuries and to elucidate the detailed causes of these injuries, the affected nerves, and the type of surgical procedures for treatment. Methods This retrospective study included 232 consecutive patients who underwent surgical treatment for peripheral nerve palsy or nerve injury between 2006 and 2017 at our hospital. Among the 232 patients investigated, we identified 51 cases with iatrogenic nerve injuries (23 women and 28 men; mean age, 51.3 years). Among the 51 patients, 45 were referred from other hospitals, and the remaining were from our hospital. Data were summarized using descriptive statistics. Results Direct surgical damage occurred in 94% (48/51) of patients with iatrogenic nerve injuries. Such injuries mostly developed after surgery for bone fractures (33%), resection of soft tissue tumors (22%), and carpal tunnel release procedures (20%). The nerves most commonly affected in such procedures are the radial nerve (26%), median nerve (24%), and ulnar nerve (17%). The median interval of referral to our hospital after nerve injury was 5.1 months. The median interval of surgery to correct the injury was 7 months. Surgeries to correct iatrogenic nerve injuries performed at our hospital included neurolysis (55%), nerve grafts (29%), direct suture procedures (10%), and tendon transfers (6%). Conclusions We believe that wide dissemination of the results obtained in this study will reduce the incidence of iatrogenic peripheral nerve injuries and increase the speed of referrals to specialized centers.

We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine this new data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of the feasibility for a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting.

To evaluate nerve high-resolution ultrasonography (HRUS) as diagnostic tool in children with supracondylar humeral fractures (SHF)-related peripheral nerve injuries (PNIs), we selected at least one illustrative case for each upper limb nerve usually involved in SHF (i.e. median, radial and ulnar nerve), in which HRUS evaluation added a useful contribution in diagnostic and therapeutic choices. We selected four patients (3 males, 1 female, aged between 7 and 12 years). Involved nerves were median (2), radial (1) and ulnar (1). HRUS results can actively modify the management of children with SHF-related PNIs, especially when combined with clinical and EDX. HRUS should be used routinely in evaluation of children with SHF-related PNIs.

With surging numbers of patients with coronavirus disease 2019 (COVID-19) throughout the world, neuromuscular complications and rehabilitation concerns are becoming more apparent. Peripheral nerve injury can occur in patients with COVID-19 secondary to postinfectious inflammatory neuropathy, prone positioning-related stretch and/or compression injury, systemic neuropathy, or nerve entrapment from hematoma. Imaging of peripheral nerves in patients with COVID-19 may help to characterize nerve abnormality, to identify site and severity of nerve damage, and to potentially elucidate mechanisms of injury, thereby aiding the medical diagnosis and decision-making process. This review article aims to provide a first comprehensive summary of the current knowledge of COVID-19 and peripheral nerve imaging.

Background. Peripheral nerve damage is a rare complication of hip replacement surgery that severely impairs the therapeutic outcome. The aim of the present study was to determine the time needed for nerve recovery and re­storation of activity following iatrogenic damage during a primary or revision hip arthroplasty from an anterolateral approach and its relationship with the severity of damage. Materials and methods. A prospectively collected database of 1107 patients treated with primary arthroplasty and 303 patients following revision arthroplasty (mean age 63 years, range 53 to 72 years) was analysed. This included 15 cases of palsy of the peroneal branch of the sciatic nerve and 7 of the femoral nerve. The mean follow-up was 3.6 years (minimum two years). Results. The following risk factors were identified: dysplastic osteoarthritis, limb elongation, revision arthroplasty, female sex and post-traumatic osteoarthritis. All five patients demonstrating light palsy (Lovett score 3-5), and 9 out of the 17 with severe palsy (Lovett score 0-2) achieved full recovery. Of all patients, 63.6% regained nerve function after 4 weeks to 24 months (mean 17 months), with nine demonstrating complete recovery and five partial. Also, 66.6% patients regained femoral nerve function and 61.5%, sciatic nerve function. Conclusion. 1. The femoral nerve and the peroneal branch of the sciatic nerve demonstrate a similar pattern of functional recovery following damage. 2. All patients recovered from light palsy, and almost 2/3 of cases of severe palsy demonstrated partial or complete recovery. 3. Female sex is a significant risk factor.

Aim: The aim of this paper is to evaluate biomaterial cues combined with physical therapy (PT) on functional recovery in a rat sciatic nerve injury model. Materials & methods: Nerve growth conduits were filled with longitudinally aligned hyaluronic acid fibers and microspheres containing neurotrophic factor (growth factor [GF]). All animals received behavior and functional testing throughout the study, which concluded with measurement of compound muscle action potentials and contractile force of the gastrocnemius muscle. Results & conclusion: Including GF improved recovery of gross motor function and increased sensory pain sensation. During the 4 weeks that animals participated in PT, these groups showed higher static sciatic index scores. Including GF and PT has the potential to improve clinical outcomes following peripheral nerve injury.

Peripheral nerve injury is a complex condition with a variety of signs and symptoms such as numbness, tingling, jabbing, throbbing, burning or sharp pain. Peripheral nerves are fragile in nature and can easily get damaged due to acute compression or trauma which may lead to the sensory and motor functions deficits and even lifelong disability. After lesion, the neuronal cell body becomes disconnected from the axon's distal portion to the injury site leading to the axonal degeneration and dismantlement of neuromuscular junctions of targeted muscles. In spite of extensive research on this aspect, complete functional recovery still remains a challenge to be resolved. This review highlights detailed pathophysiological events after an injury to a peripheral nerve and the associated factors that can either hinder or promote the regenerative machinery. In addition, it throws light on the available therapeutic strategies including supporting therapies, surgical and non-surgical interventions to ameliorate the axonal regeneration, neuronal survival, and reinnervation of peripheral targets. Despite the availability of various treatment options, we are still lacking the optimal treatments for a perfect and complete functional regain. The need for the present age is to discover or design such potent compounds that would be able to execute the complete functional retrieval. In this regard, plant-derived compounds are getting more attention and several recent reports validate their remedial effects. A plethora of plants and plant-derived phytochemicals have been suggested with curative effects against a number of diseases in general and neuronal injury in particular. They can be a ray of hope for the suffering individuals.

The development of a successful strategy to ensure a full recovery in patients affected by peripheral nerve injury (PNI), one of the most debilitating pathologies, is, still today, a major clinical challenge. Herein, spermidine (SP), an endogenous polyamine, is employed with a dual role: as cross-linking agent for alginate (ALG) and as antioxidant and anti-inflammatory compound. In particular, micro/nanogels based on the ionic interaction between ALG and SP were obtained via ionotropic gelation. Different ALG concentrations and viscosity grades and different SP concentrations were considered. The influence of such variables on micro/nanogels size was investigated by means of a Design of Experiments (DoE) approach (full factorial design). The formation of micro/nanogels was proved by Scanning Electron Microscope (SEM) analysis and by rheological and profilometry measurements. Fourier Transform Infrared (FTIR) measurements performed on nanogels of optimal composition confirmed SP-ALG interaction. The addition of trehalose as cryoprotectant agent to nanogel dispersion was considered in view of the employment of freeze-drying process to obtain a stable product. Moreover, in vitro studies on Schwann cells proved the ability of SP of expressing antioxidant and anti-inflammatory properties, even if involved in the formation of nanogels.

Neuroanatomical tracing is considered a crucial technique to assess the axonal regeneration level after injury, but traditional tracers do not meet the needs of in vivo neural tracing in deep tissues. Magnetic resonance (MR) and photoacoustic (PA) imaging have high spatial resolution, great penetration depth, and rich contrast. Fe

Ballistic injuries to peripheral nerves are devastating injuries frequently encountered in modern conflicts and civilian trauma centers. Such injuries often produce lifelong morbidity, mainly in the form of function loss and chronic pain. However, their surgical management still poses significant challenges concerning indication, timing, and type of repair, particularly when they are part of high-energy multi-tissue injuries. To help trauma surgeons, this article first presents basic ballistic concepts explaining different types of missile nerve lesions, described using the Sunderland classification, as well as their usual associated injuries. Current controversies regarding their surgical management are then described, including nerve exploration timing and neurolysis's relevance as a treatment option. Finally, based on anecdotal evidence and a literature review, a standardized management strategy for ballistic nerve injuries is proposed. This article emphasizes the importance of early nerve exploration and provides a detailed method for making a diagnosis in both acute and sub-acute periods. Direct suturing with joint flexion is strongly recommended for sciatic nerve defects and any nerve defect of limited size. Conversely, large defects require conventional nerve grafting, and proximal injuries may require nerve transfers, especially at the brachial plexus level. Additionally, combined or early secondary tendon transfers are helpful in certain injuries. Finally, ideal timing for nerve repair is proposed, based on the defect length, associated injuries, and risk of infection, which correlate intimately to the projectile velocity.

Background Peripheral nerve injuries (PNIs) include several conditions in which one or more peripheral nerves are damaged. Trauma is one of the most common causes of PNIs and young people are particularly affected. They have a significant impact on patients’ quality of life and on the healthcare system, while timing and type of surgical treatment are of the utmost importance to guarantee the most favorable functional recovery. To date, several different classifications of PNIs have been proposed, most of them focusing on just one or few aspects of these complex conditions, such as type of injury, anatomic situation, or prognostic factors. Current classifications do not enable us to have a complete view of this pathology, which includes diagnosis, treatment choice, and possible outcomes. This fragmentation sometimes leads to an ambiguous definition of PNIs and the impossibility of exchanging crucial information between different physicians and healthcare structures, which can create confusion in the choice of therapeutic strategies and timing of surgery. Materials The authors retrospectively analyzed a group of 24 patients treated in their center and applied a new classification for PNI injuries. They chose (a) five injury-related factors, namely nerve involved, lesion site, nerve type (whether motor, sensory or mixed), surrounding tissues (whether soft tissues were involved or not), and lesion type—whether partial/in continuity or complete. An alphanumeric code was applied to each of these classes, and (b) four prognostic codes, related to age, timing, techniques, and comorbidities. Results An alphanumeric code was produced, similar to that used in the AO classification of fractures. Conclusions The authors propose this novel classification for PNIs, with the main advantage to allow physicians to easily understand the characteristics of nerve lesions, severity, possibility of spontaneous recovery, onset of early complications, need for surgical treatment, and the best surgical approach. Level of evidence: according to the Oxford 2011 level of evidence, level 2.

Peripheral nerve injuries (PNI) are a major clinical problem. In general, PNI results from motor vehicle accidents, lacerations with sharp objects, penetrating trauma (gunshot wounds) and stretching or crushing trauma and fractures. They can result in significant morbidity, including motor and/or sensory loss, which can affect significantly the life of the patient. Currently, the standard surgical technique for complete nerve transection is end-to-end neurorrhaphy. Unfortunately, there is segmental loss of the nerve trunk in some cases where nerve mobilization may permit end-to-end neurorrhaphy if the gap is less than 1 cm. When the nerve gap exceeds 1 cm, autologous nerve grafting is the gold standard of treatment. But in light of limited availability and concerned donor site morbidity, other techniques have been used: vascularized nerve grafts, cellular and acellular allografts, nerve conduits, nerve transfers and end-to-side neurorrhaphy. This review intends to present an overview of the literature on the applications of these techniques in repair of peripheral nerve injuries. This article also focuses on preoperative assessment, surgical timing, available options and future perspectives.

Background and aims Aside from the long term side effects of a nerve injury in the upper extremity with devastating consequences there is often the problem of chronic neuropathic pain. The studies concerning the prevalence of persistent pain of neuropathic origin after peripheral nerve injuries are sparse. The prevalence and risk factors associated with chronic neuropathic pain after nerve injuries in the upper extremity were assessed. Methods A standardized data collection template was employed prospectively and retrospectively for all patients with traumatic nerve injuries accepted at the Hand Surgery Department, Uppsala, Sweden between 2010 and 2018. The template included demographic data, pain diagnosis, type of injured nerve, level of injury, date of the lesion and repair, type of procedure, reoperation, time since the procedure, S-LANSS questionnaire (Self report-Leeds Assessment of Neuropathic Symptoms and Signs), RAND-36 (Item short form health survey), QuickDASH (Disability of Shoulder, Arm and Hand) and additional questionnaires concerned medication, pain intensity were sent to 1,051 patients with nerve injuries. Partial proportional odds models were used to investigate the association between persistent pain and potential predictors. Results More than half of the patients undergoing a surgical procedure developed persistent pain. Prevalence of neuropathic pain was 73% of the patients with pain (S-LANSS ≥ 12 or more). Multivariate analysis indicated that injury of a major nerve OR 1.6 (p = 0.013), years from surgery OR 0.91 (p = 0.01), younger age OR 0.7 (p p = 0.019). Conclusions A high prevalence of chronic pain and neuropathic pain with a negative impact on quality of life and disability were found in patients after traumatic nerve injury. Major nerve injury, younger age and less time from surgery were predictors for chronic pain.

Background Peripheral nerve injuries are severe conditions with potential lifelong impairment, which is especially meaningful for the pediatric population. Knowledge on prevalence, injury mechanisms and concomitant injuries is, therefore, of utmost importance to increase clinician awareness and enable early diagnosis and treatment. As current literature on pediatric nerve lesions and concomitant injuries is scarce, we aimed to analyze all details of our patient population. Methods A total of 110 667 patients treated at our level 1 trauma center from 2012 to 2021 were evaluated for pediatric peripheral nerve injuries, causes, concomitant injuries and assessed for lesion classification (in continuity, partial lesion, dissection) and further relevant intraoperative findings. Results We found 5026 patients of all ages with peripheral nerve lesions, whereof 288 were pediatric, resulting in a prevalence of 5.7% of pediatric patients with nerve injuries. Mean age was 12.4 ± 4.6 years. Most common lesions were digital nerves (48.2%), followed by median (14.9%), ulnar (14.6%), radial (8.8%), peroneal nerve (5.2%) and brachial plexus injuries (2.1%). Of all pediatric nerve injuries, 3.8% were iatrogenic, only 30.2% had preserved continuity and 47.3% a concomitant vessel injury. Fractures were accompanied in 22.6%. Discussion We observed that a large proportion of injures had complete transections, often accompanied by concomitant vessel injuries especially in distally located injuries, highlighting the importance of early surgical exploration. Radial, ulnar and lower extremity nerve injuries were often associated with fractures. Early surgical nerve repair is key to improve motor and sensory outcomes. Knowledge on mechanisms and concomitant injuries facilitates timely diagnosis and treatment, thereby potentially preventing lifelong impairment.

The slow rate of neuronal regeneration that follows peripheral nerve repair results in poor recovery, particularly where reinnervation of muscles is delayed, leading to atrophy and permanent loss of function. There is a clear clinical need to develop drug treatments that can accelerate nerve regeneration safely, restoring connections before the target tissues deteriorate irreversibly. The identification that the Rho/Rho-associated kinase (ROCK) pathway acts to limit neuronal growth rate is a promising advancement towards the development of drugs. Targeting Rho or ROCK directly can act to suppress the activity of this pathway; however, the pathway can also be modulated through the activation of upstream receptors; one of particular interest being peroxisome proliferator-activated receptor gamma (PPAR-γ). The connection between the PPAR-γ receptor and the Rho/ROCK pathway is the suppression of the conversion of inactive guanosine diphosphate (GDP)-Rho to active guanosine triphosphate GTP-Rho, resulting in the suppression of Rho/ROCK activity. PPAR-γ is known for its role in cellular metabolism that leads to cell growth and differentiation. However, more recently there has been a growing interest in targeting PPAR-γ in peripheral nerve injury (PNI). The localisation and expression of PPAR-γ in neural cells following a PNI has been reported and further in vitro and in vivo studies have shown that delivering PPAR-γ agonists following injury promotes nerve regeneration, leading to improvements in functional recovery. This review explores the potential of repurposing PPAR-γ agonists to treat PNI and their prospective translation to the clinic.

Major peripheral nerve injuries are devastating and represent a very challenging clinical problem. Despite many years of advancement in peripheral nerve research, results so far have been fair at best, with only 50% of patients regaining useful function. Advancement of techniques in imaging, better understanding of the physiology of nerve recovery, improved repair and grafting options, and secondary reconstructive techniques, including tendon and nerve transfers, have helped facilitate a degree of more effective treatment. This article presents current concepts regarding the principles of management, expected outcomes, and new advancements in major upper extremity peripheral nerve injuries.

The collapse of the Syrian healthcare system during the civil war led numerous citizens to cross the Syrian-Israeli border to seek medical care.To describe the epidemiology of peripheral nerve injuries (PNIs) sustained in war, their management, and short-term outcomes.A retrospective case series study was conducted on 45 consecutive patients aged 25.7 ± 9.3 years. These patients were referred to the hand surgery unit of the department of orthopedic surgery and traumatology at Galilee Medical Center between December 2014 and June 2018. Median time between injury and presentation was 60 days. Injury pattern, additional injuries, surgical findings and management, complications, and length of hospital stay were extracted from medical records.Most injuries were blast (55.6%) followed by gunshot injuries (37.8%). There were 9 brachial plexus injuries, 9 sciatic nerve injuries, and 38 PNIs distal to the plexus: specifically 20 ulnar, 11 median, and 7 radial nerve injuries. In the latter group, neurotmesis or axonotmesis was found in 29 nerves. Coaptation was possible in 21 nerves necessitating cable grafting in 19. A tendon transfer was performed for 13 peripheral nerves, occasionally supplementing the nerve repair. The patients returned to their country after discharge, average follow-up was 53.6 ± 49.6 days.For nerve injuries sustained in war, early surgical treatment and providing adequate soft tissue conditions is recommended. Tendon transfers are useful to regain early function.

While there is now keen interest in restoring function lost through irreparable nerve injury by performing nerve-to-nerve transfer, for some time to come, tendon transfers will remain the primary reconstructive procedure for paralytic injuries of the upper limb. A career spanning more than 50 years has permitted the author to try many tendon transfers promoted by past and present colleagues for the three common nerve injuries (median, radial and ulnar) affecting hand function and, eventually, to settle upon those which have provided the most predictable and consistent outcomes. This article describes the author’s preferred tendon transfers for high radial and low median and ulnar palsies, providing the rationale behind these choices, operative details supplemented with illustrations, technical tips and advice regarding postoperative rehabilitation.

Introduction: The iatrogenic effects of repairing peripheral nerve injuries (PNIs) with autografts (AGTs) encouraged the present study to involve a new approach consisting of grafting xenogeneic prerecellularized allogeneic cells instead of AGTs. Methods: We compared sheep's AGT regenerative and functional capacity with decellularized human nerves prerecellularized with allogeneic Schwann-like cell xenografts (onwards called xenografts). Mesenchymal stem cells were isolated from ovine adipose tissue and induced in vitro to differentiate into Schwann-like cells (SLCs). Xenografts were grafted in ovine sciatic nerves. Left sciatic nerves (20 mm) were excised from 10 sheep. Then, five sheep were grafted with 20 mm xenografts, and five were reimplanted with their nerve segment rotated 180° (AGT). Results: All sheep treated with xenografts or AGT progressively recovered the strength, movement, and coordination of their intervened limb, which was still partial when the study was finished at sixth month postsurgery. At this time, numerous intrafascicular axons were observed in the distal and proximal graft extremes of both xenografts or AGTs, and submaximal nerve electrical conduction was observed. The xenografts and AGT-affected muscles appeared partially stunted. Conclusions: Xenografts and AGT were equally efficacious in starting PNI repair and justified further studies using longer observation times. The hallmarks from this study are that human xenogeneic acellular scaffolds were recellularized with allogenic SCL and were not rejected by the nonhuman receptors but were also as functional as AGT within a relatively short time postsurgery. Thus, this innovative approach promises to be more practical and accessible than AGT or allogenic allografts and safer than AGT for PNI repair.

Peripheral nerve injuries requiring surgical repair affect over 100,000 individuals in the US annually. Three accepted methods of peripheral repair include end-to-end, end-to-side, and side-to-side neurorrhaphy, each with its own set of indications. While it remains important to understand the specific circumstances in which each method is employed, a deeper understanding of the molecular mechanisms underlying the repair can add to the surgeon’s decision-making algorithm when considering each technique, as well as help decide nuances in technique such as the need for making epineurial versus perineurial windows, length and dept of the nerve window, and distance from target muscle. In addition, a thorough knowledge of individual factors that are active in a particular repair can help guide research into adjunct therapies. This paper serves to summarize the similarities and divergences of the three commonly used nerve repair strategies and the scope of molecular mechanisms and signal transduction pathways in nerve regeneration as well as to identify the gaps in knowledge that should be addressed if we are to improve clinical outcomes in our patients.

Ischemic nerve injuries are a rare complication of peripheral nerve blocks, for which there are limited effective treatment options. Hyperbaric oxygen therapy (HBOT) is a unique medical intervention which improves tissue perfusion to treat conditions of relative ischemia by way of exposure to oxygen at supra-atmospheric partial pressures. While the application of HBOT has been evidenced for other medical conditions of relative tissue ischemia, its role in the treatment of peripheral nerve injury remains unclear. This scoping review seeks to characterize rehabilitative outcomes when HBOT is applied as an adjunct therapy in the treatment of ischemic peripheral nerve injuries.

Peripheral nerve injuries are one of the most common and costly injuries especially in the young population. In this study, it is aimed to determine the histological role of epidermal growth factor (EGF) in nerve regeneration with an acute damage made on sciatic nerve in the rabbit model.We used 18 New Zealand rabbits (nine in control group and nine in experimental group). Each group was divided into two groups consisting of five rabbits planned for diameter measurement and four rabbits planned for spatial measurement. The sciatic nerve exploration in the right flank of each animal, full-thickness nerve damage, and then epineural repair was made by a single researcher. 10 µg/kg EGF was given to the repair area of the experimental group and five more EGF injections were given to the experimental group every other day postoperatively. In the control group, we used saline solution. Rabbits were observed for 8 weeks. During follow-up, two rabbits died. At the end of 8 weeks, the nerve tissue of each animal was evaluated histologically and morphologically.In the experimental group consisting of five rabbits, the mean thickness of connective tissue (epineurium+ mesoneurium) was 156,867 µm; while, in the control group, the thickness was 25,170 µm. In the other groups, the numerical increase in epineurium and mesoneurium areas was detected in the EGF (+) group as a result of the comparative spatial measurements. Epineurium and mesoneurium enlargement was observed in the EGF-given group. Adipocyte and capillary increase was observed in connective tissue.EGF increases epineurium and mesoneurium diameters in peripheral connective tissue in acute peripheral nerve injury regeneration. However, further studies are needed to understand this effect clinically and physiologically.

Peripheral nerve injuries are a rare but serious complication of perioperative care, for which there are limited effective treatment options. Hyperbaric oxygen therapy (HBOT) is a unique medical intervention which improves tissue perfusion to treat conditions of relative ischemia by way of exposure to oxygen at supra-atmospheric partial pressures. While the application of HBOT has been evidenced for other medical conditions of relative tissue ischemia, its role in the treatment of perioperative peripheral nerve injury remains unclear. This scoping review seeks to characterize rehabilitative outcomes when HBOT is applied as an adjunct therapy in the treatment of peripheral nerve injuries.

Millions of people worldwide are affected by peripheral nerve injuries (PNI), involving billions of dollars in healthcare costs. Common outcomes for patients include paralysis and loss of sensation, often leading to lifelong pain and disability. Engineered Neural Tissue (EngNT) is being developed as an alternative to the current treatments for large-gap PNIs that show underwhelming functional recovery in many cases. EngNT repair constructs are composed of a stabilised hydrogel cylinder, surrounded by a sheath of material, to mimic the properties of nerve tissue. The technology also enables the spatial seeding of therapeutic cells in the hydrogel to promote nerve regeneration. The identification of mechanisms leading to maximal nerve regeneration and to functional recovery is a central challenge in the design of EngNT repair constructs. Using in vivo experiments in isolation is costly and time-consuming, offering a limited insight on the mechanisms underlying the performance of a given repair construct. To bridge this gap, we derive a cell-solute model and apply it to the case of EngNT repair constructs seeded with therapeutic cells which produce vascular endothelial growth factor (VEGF) under low oxygen conditions to promote vascularisation in the construct. The model comprises a set of coupled non-linear diffusion-reaction equations describing the evolving cell population along with its interactions with oxygen and VEGF fields during the first 24h after transplant into the nerve injury site. This model allows us to evaluate a wide range of repair construct designs (e.g. cell-seeding strategy, sheath material, culture conditions), the idea being that designs performing well over a short timescale could be shortlisted for in vivo trials. In particular, our results suggest that seeding cells beyond a certain density threshold is detrimental regardless of the situation considered, opening new avenues for future nerve tissue engineering., Author summary Mathematical models are increasingly gaining traction in biomedical sciences in general and in peripheral nerve repair in particular. These models can both help to unveil mechanisms underlying nerve regeneration post-injury and inform the design of new repair strategies, while continuously being improved through experiments and clinical data. In particular, cell-solute models provide flexible, computationally-efficient frameworks that enable access to spatio-temporal information difficult to reach in vivo in nerve repair scenarios. In this work, we derive such a model and apply it to the case of Engineered Neural Tissue repair constructs after their transplant into the nerve injury site. One key feature of such repair constructs is the spatial seeding of therapeutic cells capable of producing signalling molecules that promote nerve regeneration. We simulate the activity of such cells and evaluate, after 24h, cell survival and signalling molecule output for a range of nerve repair construct designs. The underlying hypothesis is that designs performing well at such short timescales could be shortlisted for in vivo trials, the latter being costly and time-consuming. Our results suggest that seeding cells beyond a certain density threshold is detrimental regardless of the situation considered, opening new avenues for future nerve repair construct design.

To assess rates of peripheral nerve injuries (PNI) in sport, exercise, and recreational activities.The National Electronic Injury Surveillance System (NEISS) was used to query nerve injuries presenting to emergency departments across the United States. Identified injuries were stratified to those with product codes associated with exercise, sports, or recreation. Injuries only to the upper and lower extremities were included as cranial and spinal cord injuries were excluded. PNI was analyzed by age, sex, sport/recreational activity, race, and evaluated for incidence rates by year and activity. Statistical significance was considered to be P 0.05.Between 2009-2018, 551,612 patients presented with PNI from which 120,675 (21.9%) were associated with exercise, sports, or recreation. PNI significantly increased between 2009-2018 (p = 0.002) with an overall incidence rate of 36.9 (95% confidence interval: 28.6, 45.2) per 1,000,000 person-years. A majority of PNI occurred through exercise (n = 56,328, 46.7%). PNI peaked in the fourth and fifth decades in males and females, respectively, with males accounting for significantly more than females (incidence rate ratio: 1.52, 95% confidence interval: 1.18, 1.86; p 0.0001). White patients had a majority of PNI at 49.3% though African-Americans carried the highest incidence rate at 30.4 (95% confidence interval: 23.8, 36.9) per 1,000,000 person-years. Football had the highest proportion of PNI until age 19 (17.3%) as exercise carried the highest proportion for those 20 and older ranging from 27.9% to 53.8% of PNI.PNIs are rising with participation in exercise, sports, and recreation over this 10-year study period. Injuries predominantly occurred in football for those under 20 and exercise for those 20 and older. Precautions and appropriate training are necessary for individuals participating in high-intensity exercise, sports, or recreation to limit the risk of a devastating neurological injury.

Purpose Combat-sustained peripheral nerve injuries (CSPNIs) are often the result of high-energy blast mechanisms and are increasing in frequency and severity among US forces engaged in contemporary warfare. The purpose of this study was to describe CSPNIs and report outcomes after evaluation in a military multidisciplinary peripheral nerve clinic. We hypothesized that a shorter time to evaluation by a multidisciplinary peripheral nerve team would improve outcomes. Methods The Peripheral Nerve Consortium (PNC) maintains an electronic database of all active duty service members who sustained a peripheral nerve injury (PNI) and were treated by the PNC between 2004 and 2009. This database was queried for service member demographic information, injury characteristics, wounding patterns, CSPNI description, surgical procedures, and Medical Research Council final motor and sensory outcome. Results Among the 104 service members treated by the PNC in the 6-year period reviewed, there were 138 PNIs. Average age was 27 years, time to initial evaluation by the PNC was 4 (±7) months, and average follow-up was 18 (±18) months. Associated injuries included fractures (31.1%), multiple PNIs (76.8%), vascular injury (30.4%), and traumatic brain injury (34.1%). There was no association between Sunderland classification and time to evaluation, mechanism of injury, or nerve injured. However, Sunderland classification was correlated with final motor and final sensory scores. Service members with better final sensory score (S1 or S2) had shorter time to initial evaluation than did patients with a final sensory score of S0 ( Conclusions Service members with more severe initial injuries had worse final outcomes. Although timely referral does not occur for most CSPNIs, a shorter time to presentation also led to improved sensory recovery. Complex combat-sustained PNIs may be best understood and treated within a multidisciplinary team. Type of study/level of evidence Prognostic IV.

Background Peripheral nerve injuries are usually not lethal but may cause serious neurological deficits if not treated properly. The aim of this study is to present our patients who underwent surgical treatment for peripheral nerve trauma in the past 10 years and to discuss their results in light of the literature. Methods The clinical and electrophysiological results of 182 patients who underwent surgical treatment in our department between 2010 and 2019 were retrospectively analyzed. All surgeries were performed using intraoperative nerve action potentials (NAP) recordings. Demographic characteristics, etiologies, surgical timing, and results of surgical treatment were recorded. Results A total of 199 surgical interventions were performed in 182 patients with peripheral nerve trauma within 10 years. 162 patients were male, 20 were female and the mean age was 29.34 years for males and 30.2 years for females. The sciatic nerve trauma was the most common in men and peroneal nerve injury women. The most common cause of trauma was gunshot wounds in menand blunt/sharp traumas in women. External and internal neurolysis was the most common surgical technique, followed by epineural anastomosis and sural nerve grafting. 155 of 182 patients showed partial neurological improvement within 3 months after surgery, while 27 had no change in their neurological condition. Conclusion Men are more frequently exposed to peripheral nerve trauma than women. Severe partial nerve lesions mostly benefit from surgical treatment, and neurolysis has become the most preferred method of surgical treatment. Intraoperative NAP recordings provide better clinical outcomes. Neurological improvement may not always be in correlation with electrophysiological improvement.

This article reviews the clinical results that can be obtained after repair of a traumatic peripheral nerve injury in the pediatric population. A systematic review of the published literature has been made. Functional outcome after major nerve injuries is sometimes disappointing in adults. However, children have been reported to experience much better functional results after nerve repair than adults. Moreover, recovery generally is faster in children. The superior capacity of children’s central nervous system to adapt to external or internal environmental changes (neural plasticity) and the shorter recovery distance from the axon repair site to the target muscle are claimed to be crucial determinants of their favorable outcomes. Moreover, even in the pediatric population, it has been demonstrated that functional results are better the younger the patient is, including better clinical results in those injured in early childhood (< 6 years old) than in those injured in adolescence. Other favorable prognostic factors include the type of nerve injury (with complete transections doing less well than crush injuries) and the timing of surgery (with better outcomes after early repairs). All efforts should be done to repair in a timely and adequate fashion traumatic peripheral nerve injuries in children, as the results are good.

ObjectiveTo systematically evaluate the literature on the therapeutic use of Schwann cells (SC) in the repair of peripheral nerve injuries.MethodsThe Cochrane Library and PubMed databases were searched using terms [(“peripheral nerve injury” AND “Schwann cell” AND “regeneration”) OR (“peripheral nerve injuries”)]. Studies published from 2008 to 2022 were eligible for inclusion in the present study. Only studies presenting data from in-vivo investigations utilizing SCs in the repair of peripheral nerve injuries qualified for review. Studies attempting repair of a gap of ≥10 mm were included. Lastly, studies needed to have some measure of quantifiable regenerative outcome data such as histomorphometry, immunohistochemical, electrophysiology, or other functional outcomes.ResultsA search of the PubMed and Cochrane databases revealed 328 studies. After screening using the abstracts and methods, 17 studies were found to meet our inclusion criteria. Good SC adherence and survival in conduit tubes across various studies was observed. Improvement in morphological and functional outcomes with the use of SCs in long gap peripheral nerve injuries was observed in nearly all studies.ConclusionBased on contemporary literature, SCs have demonstrated clear potential in the repair of peripheral nerve injury in animal studies. It has yet to be determined which nerve conduit or graft will prove superior for delivery and retention of SCs for nerve regeneration. Recent developments in isolation and culturing techniques will enable further translational utilization of SCs in future clinical trials.

Background and importance In cases of severe nerve trauma with significant local soft tissue damage, identification and subsequent repair of nerve stumps can pose a technical challenge. Ultrasound (US) localization in peripheral nerve surgery has recently become popular. We present a case report illustrating the use of needle-wire localization systems to identify proximal and several distal branches of an injured femoral nerve with a large segmental defect in order to illustrate how such techniques can be used to make surgical repair more efficient, particularly with identifying the distal stump(s). Clinical presentation We illustrate a case of a 16-yr-old female involved in a traumatic accident that lead to a severe injury of the femoral nerve and artery. The patient presented with a 7.3-cm defect between the proximal and distal aspect of the femoral nerve and its branches, respectively. High-resolution US was used to identify the proximal, large femoral nerve, and 3 distal stumps. By enlisting our musculoskeletal radiology team, we were able to trace distal branches of the femoral nerve and see their target muscles. Three separate US flexible needles were used to locate small muscular branches of the femoral nerve and 1 to locate the proximal stump. Intraoperatively, the localization wires allowed for safe and efficient dissection of proximal and distal nerve stumps in a significantly scarred and edematous plane. Conclusion US-guided needle-wire localization has shown promise in identifying the distal stumps and minimizing tissue dissection. Preoperative US guidance significantly aided in nerve repair for this severe injury without increasing morbidity.

One of the major challenges in the development of a larger and longer nerve conduit for peripheral nerve repair is the limitation in oxygen and nutrient diffusion within the tissue after transplantation preventing Schwann cell and axonal migration. This restriction is due to the slow neovascularization process of the graft starting from both nerve endings. To overcome this limitation, we propose the design of a living tissue-engineered nerve conduit made of an internal tube with a three-dimensional structure supporting axonal migration, which is inserted inside a hollow external tube that plays the role of an epineurium and is strong enough to be stitched to the severed nerve stumps. The internal tube is made of a rolled living fibroblast sheet and can be seeded with endothelial cells to promote the formation of a network containing capillary-like structures which allow rapid inosculation with the host nerve microvasculature after grafting. Human nerve conduits were grafted in immunodeficient rats to bridge a 15 mm sciatic nerve gap. Human capillaries within the pre-vascularized nerve conduit successfully connected to the host circulation 2 weeks after grafting. Twenty-two weeks after surgery, rats transplanted with the nerve conduits had a similar motor function recovery compared to the autograft group. By promoting rapid vascularization of the internal nerve tube from both ends of the nerve stumps, this endothelialized nerve conduit model displays a favorable environment to enhance axonal migration in both larger caliber and longer nerve grafts.

Summary Artificial and non-artificial nerve grafts are the gold standard in peripheral nerve reconstruction in cases with extensive loss of nerve tissue, particularly where a direct end-to-end suture or an autologous nerve graft is inauspicious. Different materials are marketed and approved by the US Food and Drug Administration (FDA) for peripheral nerve graft reconstruction. The most frequently used materials are collagen and poly(DL-lactide-ε-caprolactone). Only one human nerve allograft is listed for peripheral nerve reconstruction by the FDA. All marketed nerve grafts are able to demonstrate sufficient nerve regeneration over small distances not exceeding 3.0 cm. A key question in the field is whether nerve reconstruction on large defect lengths extending 4.0 cm or more is possible. This review gives a summary of current clinical and experimental approaches in peripheral nerve surgery using artificial and non-artificial nerve grafts in short and long distance nerve defects. Strategies to extend nerve graft lengths for long nerve defects, such as enhancing axonal regeneration, include the additional application of Schwann cells, mesenchymal stem cells or supporting co-factors like growth factors on defect sizes between 4.0 and 8.0 cm.

Entrapment neuropathies are infrequent in children, and therefore remain unrecognized. The incidence of radial, median, and cubital mononeuropathies are all similar. Despite the rarity of such cases, extensive, albeit scattered, literature has accumulated concerning entrapment neuropathies in children. To the literature concerning entrapment neuropathies in children. A systematic review of the existing literature has been made. The management of chronic pediatric pain is very important in such patients to prevent youths from experiencing prolonged absences from school, sports, or other productive activities, and limit the psychological burden of chronic disease. Nonsurgical treatment of both cubital and carpal tunnel syndromes has been disappointing in pediatric patients, with only limited success; and, to date, there is no clear explanation for the outcome differences generated by nonsurgical management between adults and youths. Simple decompression of the ulnar nerve at the elbow also has much higher rates of failure in children than in adults. The presence of an entrapment neuropathy (specially carpal tunnel syndrome) in a pediatric-age patient should alert medical care providers to the potential of some underlying genetic condition or syndrome.

Peripheral nerve tumors type, inciedence and treatment in the pediatric population should be analyzed. We have performed an extense literature review of this subject. incidence and distribution are similar to those observed in adults. The most common peripheral nerve tumors in children are neurofibromas and schwannomas. Malignant peripheral nerve sheath tumors are also observed, specially associated with genetic syndromes, like neurofibromatosis and Carney complex. In this review, peripheral nerve tumors have been divided into three categories to aid with understanding: reactive and hyperplastic lesions, benign tumors, and malignant tumors. The most frequent lesions have been described.