Narrow Results

Background: Decellularised nerve transplantation has limited therapeutic efficacy for peripheral nerve injuries. In this study, we tested the hypothesis that nerve regeneration can be promoted by increasing blood circulation to the decellularised nerve through the surrounding blood-flow environment.

Methods: We transplanted 20 mm decellularised nerves into sciatic nerve defects in Sprague–Dawley rats (female, 12 weeks old). In the intramuscular group, the decellularised nerve was implanted into the biceps femoris muscle and covered with the muscle to provide blood circulation. In the avascular group, the decellularised nerve was sutured to the sciatic nerve and the surrounding nerve bed was cauterised to create a non-bleeding field. In the intramuscular without repair group, the decellularised nerve was implanted in the biceps femoris muscle, but not sutured to the sciatic nerve. Axonal elongation and angiogenesis were evaluated immunohistochemically using anti-neurofilament, anti-S100 and anti-CD31 antibodies in sagittal and transverse sections of the nerve 3 weeks later.

Results: In the intramuscular group, the number of neurofilaments per unit area and S100 were higher than those in the other groups (p < 0.05). CD31 staining was predominant in the intramuscular group. Axial images of the nerves confirmed the localisation of CD31-positive cells, and positive cells were found in the centre of the decellularised nerves in the intramuscular group.

Conclusions: Decellularised nerve grafts wrapped with vascular-rich tissue promoted nerve regeneration by enhancing angiogenesis in transplanted nerve grafts and preventing ischemia in the centre of the nerve graft.

Background: Peripheral nerve stimulation (PNS) has emerged as a promising treatment for refractory neuropathic pain in the upper extremities, particularly for patients unresponsive to conventional therapies. This systematic review and meta-analysis aims specifically to evaluate the effectiveness and safety of nerve stimulation of the brachial plexus (BP) for managing chronic neuropathic pain in the upper extremities.

Methods: A comprehensive literature search was conducted following PRISMA guidelines across major databases, including PubMed, Scopus and Embase. Five studies met the inclusion criteria, encompassing a total of 157 patients with BP or other peripheral nerve injuries. The primary outcome measures included pain reduction and quality of life improvement, assessed through validated pain scales such as the Numerical Rating Scale (NRS) and patient-reported outcomes.

Results: This meta-analysis demonstrated significant reductions in pain scores following BP nerve stimulation (MD: −4.88, 95% CI: −5.80 to −3.96, p < 0.05). Additionally, improvements in quality of life were observed, with over 30% enhancement in Short Form (SF)-36 scores. The overall complication rate was low, with only 9.2% of patients experiencing adverse events, such as lead migration or postoperative infection.

Conclusions: These findings suggest that PNS at the level of the BP is both a safe and effective intervention for the management of refractory neuropathic pain in the upper extremities.

Level of Evidence: Level IV (Therapeutic)

Most deep brain stimulators apply rectangular monophasic voltage pulses. By modifying the stimulus shape, it is possible to optimize stimulus efficacy and find the best compromise between clinical effect, minimal side effects and power consumption of the stimulus generator. In this study, we compared the efficacy of three types of charge-balanced biphasic pulses (CBBPs, nominal duration 100 μs) in isolated sciatic nerves and in in vitro hippocampal brain slices of the rat. Using these two models, we tested the efficacy of several stimulus shapes exclusively on axons (in the sciatic nerve) and compared the effect with that of stimuli in the more complex neuronal network of the hippocampal slice by considering the stimulus-response relation. We showed that (i) adding an interphase gap (IPG, range 100–500 μs) to the CBBP enhances stimulus efficacy in the rat sciatic nerve and (ii) that this type of stimuli (CBBP with IPG) is also more effective in hippocampal slices. This benefit was similar for both models of voltage and current stimulation. In our two models, asymmetric CBBPs were less beneficial. Therefore, CBBPs with IPG appear to be well suited for application to DBS, since they enhance efficacy, extend battery life and potentially reduce harmful side effects.

Electrical stimulation of the peripheral nervous system is a promising therapeutic option for several conditions; however, its effects on tissue and the safety of the stimulation remain poorly understood. In order to devise stimulation protocols that enhance therapeutic efficacy without the risk of causing tissue damage, we constructed computational models of peripheral nerve and stimulation cuffs based on extremely high-resolution cross-sectional images of the nerves using the most recent advances in computing power and machine learning techniques. We developed nerve models using nonstimulated (healthy) and over-stimulated (damaged) rat sciatic nerves to explore how nerve damage affects the induced current density distribution. Using our in-house computational, quasi-static, platform, and the Admittance Method (AM), we estimated the induced current distribution within the nerves and compared it for healthy and damaged nerves. We also estimated the extent of localized cell damage in both healthy and damaged nerve samples. When the nerve is damaged, as demonstrated principally by the decreased nerve fiber packing, the current penetrates deeper into the over-stimulated nerve than in the healthy sample. As safety limits for electrical stimulation of peripheral nerves still refer to the Shannon criterion to distinguish between safe and unsafe stimulation, the capability this work demonstrated is an important step toward the development of safety criteria that are specific to peripheral nerve and make use of the latest advances in computational bioelectromagnetics and machine learning, such as Python-based AM and CNN-based nerve image segmentation.

Any restoration of hand function following tendon and nerve injury has to include the repair or replacement of the hand's ability to perform a great many tasks. It is hard at first to appreciate fully the loss that occurs with flexor tendon injury. With loss of flexor tendons operating at the fingers or thumb, they cannot be fully closed and the hand is impaired for grasp and release as it interfaces with objects. But, sensibility can also be compromised from tendon injury even without direct injury to nerve, as object recognition in the absence of vision requires finger movement. When peripheral nerve injury is combined with flexor tendon injury, sensibility is directly impaired. There is a loss in the sense of finger or thumb position, pain, temperature, and touch/pressure recognition, in addition to the tendon injury.

The purpose of this study was to clarify the effect of an absorbable oxidised regenerated cellulose sheet (AORCS) for prevention of neural adhesion. Rabbit sciatic nerve was exposed at the middle of the thigh and the neural bed was coagulated by a bipolar coagulator to establish an adhesion model. Coagulation only was Group A (n = 8), coagulation and wrapping the sciatic nerve with an AORCS was Group B (n = 8), and an intact nerve was Group C (n = 16). Six weeks later, each group was estimated. Adhesion between the nerve and neural bed, and intraneural fibrosis were seen in Group A. However, there was little adhesion and fibrosis in Group B. Although the electrophysiological study showed a small significant difference, AORCS clearly prevented the adhesion in the histological study. Hence, AORCS might be useful as an additional treatment during nerve surgery.

The prognosis and speed of peripheral nerve recovery depend very much on the level of injury, severity of injury, the surgical intervention and the subsequent rehabilitative process. Many high level injuries may take years or months for the affected peripheral nerve to recover. Prolonged muscle imbalance causes joint contractures and over-stretching of denervated muscles. Without proper care, hand function recovery may be limited even the nerve regenerated afterwards.

During the nerve regeneration period, splinting is one of the most useful modality to minimise deformities, prevent joint contractures and substitute loss motor control. Proper splinting encourages early use of the injured hand in daily activities. There are different types of splinting design for median nerve palsy, ulnar nerve palsy and radial nerve palsy. Dynamic splinting techniques are frequently employed to allow early prehension activities. Other therapeutic techniques, including pressure garment and sensory re-education are useful to enhance better functional return after nerve repair.

Peripheral nerve injury changes the kinetics of neurotrophins. The production of several neurotrophins increases at the site of injury. Although numerous reports have described changes in neurotrophins over time in areas of nerve injury, neurotrophin mRNA is present at very low levels in target tissues, making accurate quantitation difficult. We developed a reverse transcription–polymerase chain reaction/high-performance liquid chromatography (RT-PCR/HPLC) method that enables accurate quantitation of neurotrophin mRNA. We then attempted to quantitate mRNA levels for nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) produced by skeletal muscle innervated by the sciatic nerve following transection and reattachment of the nerve in mice. In addition, wet weights of the muscle were measured and changes in weight over time were determined. The results indicated that neurotrophin production in muscle increases as a result of peripheral nerve denervation due to transection, and decreases with nerve regeneration and reinnervation resulting from reattachment.

Objective: The objective of this study is to clarify the differences in physiological responses following the different modality of repetitive compressions versus continuous compression (CC) of the peripheral nerve. Methods: Thirty-two rabbits were used. Under anesthesia, four conditions of compression; CC, low-frequency release compression (LFR, one second release time every 30 s), high-frequency release compression (HFR, one second release time every 10 s), and high-frequency compression (HFC, one second compression time every 10 s) were each applied with 80mmHg of pressure for 90min to the sciatic nerve. Compound nerve action potential (CNAP) and nerve blood flow were evaluated from the beginning of compression to 90min after compression release. Endoneurial microvascular permeability was evaluated histologically. Results: During compression, the nerve blood flow and the amplitude of CNAP decreased for all four groups. There were significant delays in the recovery of the amplitude and nerve blood flow in the LFR and HFR groups compared to CC group ($P<0.05$). Endoneurial edema was observed in the repetitive compression groups. Conclusions: Even if the overall compression time was short, the accumulation of repetitive compression-release cycles causes to delay the recovery of nerve physiological function with endoneurial edema.

Diabetic neuropathy (DN) is, at least in part, associated with the functional attenuation of vasa nervorum, the microvascular structure of peripheral nerves. Microvascular imaging options for vasa nervorum still remain limited. In this work, optical microangiography (OMAG), a volumetric, label-free imaging technique, is utilized for characterizing, with high resolution, blood perfusion of peripheral nerve in diabetic mice. We demonstrate that OMAG is able to visualize the structure of microvasculature and to quantify the changes of dynamic blood flow and vessel diameters during administration of vessel stimulant in both diabetic and normal mice. The results indicate the potential of OMAG to assess the blood supply of nerve involved in the pathology and treatment of DN.

Background: A small number of patients develop intractable peripheral nerve pain following injury or surgery to the upper limb that is refractory to pharmacological treatment. This study reports our results of using transcutaneous peripheral nerve stimulation (TPNS), a non-invasive form of neuromodulation, to treat this difficult problem.

Methods: Seventy-two patients were treated for intractable pain in the upper limb using this technique. Electrical current was delivered transcutaneously through a handheld probe, placed on the skin overlying the affected peripheral nerve proximal to the site of pain. Pain severity was determined before and immediately after treatment by subjective patient self-assessment using a visual analogue pain scale. Pre-post treatment changes in pain severity were analysed by Student's test for paired data. Outcome in respect of overall effectiveness of this treatment, was graded according to the maximum duration of pain relief achieved.

Results: Overall, TPNS reduced pain intensity from 8.4 (SD 1.6) before treatment to 4.2 (SD 3.5) immediately after treatment, a highly significant effect ($p<0.001$). The treatment achieved cure in 8/72 (11%) of our patients and a useful therapeutic outcome (pain relief ≥ 1 day) in 27/72 (38%). The treatment failed in 37/72 (51%).

Conclusions: TPNS warrants consideration as a therapy for neuropathic pain in the upper limb after drug treatment has failed and before offering surgery or spinal root stimulation.

A 25-year-old man sustained a right-sided brachial plexus injury from a high-velocity motocross accident. Physical examination and electromyography were consistent with a pan-brachial plexopathy with no evidence of axonal continuity. The patient underwent a spinal accessory to suprascapular nerve transfer and an intercostal to musculocutaneous nerve transfer with interpositional sural nerve grafts. He recovered MRC 4/5 elbow flexion and MRC 2/5 shoulder abduction and external rotation. Twenty-two months post-injury the patient displayed a flicker of flexion of his flexor pollicis longus and flexor digitorum profundus to his index finger – he went on to recover a functional pinch. Thirty-six months post-injury the patient displayed a flicker of contraction in brachioradialis with motor unit potentials on electromyography. This case demonstrates that some patients may have capacity for functional recovery after prolonged denervation and highlights the potential impact of anatomical anomalies in the assessment and treatment of peripheral nerve injuries.

Background: Perineural adhesion is a potential complication of manipulating peripheral nerves. Using a model of median nerve manipulation in the carpal tunnel, perineural adhesion preventive effects of an alginate gel formulation were examined.

Methods: After exposing carpal tunnels of Japanese white rabbits and dissecting the median nerve, the gliding floor was excised as much as possible and the transverse carpal ligament was repaired to induce a perineural tissue reaction. Prior to wound closure, 0.5 ml of alginate gel formulation was administered into the right carpal tunnel (formulation group) and 0.5 ml of physiological saline was administered into the left carpal tunnel (control group). At 1, 2, 3, and 6 weeks after treatment, electrophysiological evaluation of thenar distal latency, macroscopic evaluation with adhesion score, and pathological evaluation of carpal tunnel cross sections were performed (N = 4–5 at each time point).

Results: Although distal latency tended to be low in the formulation group, there was no significant difference between the groups according to electrophysiological evaluation. Macroscopic evaluation revealed that the adhesion score was always lower in the formulation group than in the control group; over the course of treatment, it remained unchanged in the formulation group, but peaked at 3 weeks after treatment in the control group. In pathological evaluation, neural perfusion peaked at 2–3 weeks after treatment in both groups; neural perfusion tended to be lower in the formulation group than in the control group.

Conclusions: Results suggested that the peak tissue response associated with nerve dissection occurred 2–3 weeks after treatment and that the repair process started subsequently. The alginate gel formulation modified the surrounding environment of the nerve and promoted repair by acting as a physical barrier against perineural fibrosis. The preventive effect of alginate gel on perineural adhesion may improve treatment outcomes of constrictive neuropathy.

We describe a case of an adult patient presenting with cubital tunnel syndrome in the setting of previously undiagnosed macrodactyly. Early diagnosis and management of macrodactyly is important to help prevent symptoms associated with compromised peripheral nerves and reduce the likelihood of the permanent motor and sensory sequelae of prolonged nerve compression.

Background: Traumatic neuromas are a result of abnormal neural regeneration after nerve injury. Neuropathic pain arising from neuroma can be debilitating.

Methods: This was a retrospective review of a consecutive series of patients who presented with a painful cutaneous neuroma secondary to direct trauma or surgery. The diagnosis was made by the presence of neuropathic symptoms in the dermatome of a cutaneous nerve and a positive Tinel sign. Local anaesthetic injection was performed for confirmation of diagnosis. Each patient was offered optimisation of medical therapy and physiotherapy for desensitisation. Outpatient neuromodulation was offered as an alternative to neuroma surgery. The primary aim of treatment was symptom reduction such that neuroma surgery was no longer required.

Results: This study included 50 patients with painful cutaneous neuromas. Surgery was the commonest cause. The most frequently injured nerves were superficial radial nerve, digital nerve and dorsal ulnar cutaneous nerve, together comprising over 60% of cases. After receiving neuromodulation, 18 (36%) patients experienced sufficient symptom relief and did not wish to pursue neuroma surgery.

Conclusions: Surgery is the commonest cause of a painful cutaneous neuroma. Following optimisation of pharmacotherapy and physiotherapy, neuromodulation may offer symptom relief such that neuroma surgery may be avoided in approximately one third of cases.

Neurogenic thoracic outlet syndrome (nTOS) is caused by brachial plexus compression in the thoracic outlet. It accounts for 85%–95% of thoracic outlet syndrome (TOS) cases, which may also be caused by compression of the subclavian artery and vein. Compression occurs in the interscalene triangle, costoclavicular space or subpectoralis minor space, with congenital anomalies and repetitive overhead activities as contributing factors. Diagnosis is challenging due to overlapping symptoms with other conditions. Patients commonly report pain, numbness, tingling and weakness in the neck, shoulder and arm, exacerbated by arm elevation. Symptoms related to nTOS may manifest in the distribution of the upper (C5–C6), middle (C7) and lower plexus (C8–T1). Although widely used, provocative tests have varying degrees of sensitivity and specificity and may have high false-positive rates, complicating the diagnosis. Patterns on electrodiagnostic studies provide key diagnostic clues, such as reduced sensory response in the medial antebrachial cutaneous nerve and low compound motor action potential in the median nerve. Imaging techniques like magnetic resonance imaging (MRI), alongside procedures like diagnostic and therapeutic anterior scalene blocks, assist in identifying anatomical abnormalities and predicting surgical outcomes. Management of nTOS involves lifestyle changes, physical therapy, medication and botulinum toxin injections for symptomatic relief. Surgical options may include supraclavicular, transaxillary and infraclavicular approaches, each offering specific benefits based on patient anatomy and surgeon expertise. Minimally invasive techniques, such as video-assisted thoracoscopic surgery (VATS) and robotic surgery, enhance exposure and dexterity, leading to better outcomes. Future research should focus on developing precise diagnostic tools, understanding nTOS pathophysiology, standardising diagnostic criteria and surgical approaches, comparing long-term treatment outcomes and exploring preventive measures to improve patient care and quality of life.

Level of Evidence: Level V (Therapeutic)

Electrical stimulation has been integrated in recent decades into rehabilitation protocols following neuromuscular injuries. Existing literature supports the utilisation of prolonged or continuous stimulation generated by implantable or transcutaneous devices for chronic pain subsidence and muscle trophism maintenance, which improve outcomes following microsurgical interventions. Newer uses include brief electrical stimulation for peripheral nerve injury. Brief electrical stimulation has shown promise in expediting regeneration of both torn and crushed nerve axons in the murine model and has been incorporated into a limited number of clinical studies. Augmentation of the natural response of an injured peripheral nerve by electrical stimulation has the potential to accelerate regeneration, presumably leading to improved function and clinical outcomes. We review the existing literature on intraoperative utilisation of electrical stimulation to enhance regeneration, such as neural mechanisms of action and their microscopic effect in animal models, as well as results from initial human studies.

Level of Evidence: Level V (Therapeutic)

Background: Ulnar neuropathy after a distal radius fracture is rare and has limited reports in literature. As such, there is no consensus regarding the optimal treatment and management of such injuries. We report our experience with managing these uncommon injuries.

Methods: A retrospective review was conducted where patients presenting with ulnar neuropathy after sustaining a distal radius fracture were identified from January 2021 to December 2023 from our hospital database.

Results: A total of four patients were identified. All of them underwent surgical fixation for their respective fractures. None of them underwent immediate or delayed exploration and decompression of the ulnar nerve. All patients had clinical improvement at 3 months after their initial injuries. Three patients eventually had resolution of the neuropathy between 5 and 9 months post injury, while one had partial recovery and developed a neuroma but declined surgery due to symptoms minimally affecting work and daily activities.

Conclusions: Ulnar neuropathy after distal radius fractures may not be as rare as previously thought. Expectant management of the neuropathy would be a reasonable treatment as long as there is no evidence of nerve discontinuity or translocation and that there is clinical and/or electrodiagnostic improvement at 3–4 months after the initial injury.

Level of Evidence: Level IV (Therapeutic)