Intercostal nerve injury can occur after rib fractures, resulting in denervation of the abdominal musculature. Loss of innervation to the rectus abdominis and intercostal muscles can cause atrophy and subsequent eventration, pain, and cosmetic issues. Intercostal electrodiagnostic testing can diagnose and localize intercostal nerve damage after rib fractures at levels T7 and below. To characterize rib fracture patterns associated with intercostal nerve injury and evaluate the diagnostic and surgical utility of preoperative nerve conduction study/electromyography (NCS/EMG) findings. Eight patients with NCS/EMG-diagnosed intercostal nerve injury following rib fractures were included in the study. A total of 17 levels with intercostal nerve damage were identified on electrodiagnostic testing. Descriptive rib fracture characteristics were obtained from preoperative chest computed tomography by a single chest wall surgeon and analyzed for displacement, degree of rib separation, fracture location, and presence of intercostal muscle, lung, and retroperitoneal hernias. Preoperative electrodiagnostic testing results were correlated with computed tomography rib fracture characteristics, ultrasound measurements of rectus abdominis cross sectional thickness, and direct intraoperative intercostal nerve evaluation using an intraoperative nerve stimulator. At the level of NCS/EMG-diagnosed intercostal nerve injury, 50% ribs were displaced and 50% were nondisplaced. Two levels demonstrated evidence of intercostal hernia, one with lung hernia and one with retroperitoneal hernia. The average degree of separation of rib fractures was 1.45 cm with two ribs demonstrating 0 cm of separation. With regard to rib fracture location, 29% were posterior, 41% posterolateral, and 23% lateral. Seven of eight patients (total of 15 nerves) underwent surgical intervention in the form of neurolysis versus intercostal nerve reconstruction with allograft nerve tissue. Direct intraoperative intercostal nerve stimulation correlated with the presence of intercostal nerve injury identified on preoperative NCS/EMG findings in 12 of 15 cases (80%). Two intercostal nerves were not explored secondary to significant intercostal trauma. A single level discrepancy was identified between preoperative NCS/EMG and intraoperative findings in one case. Ultrasound measurements demonstrated an average rectus abdominis transverse cross-sectional thickness of 0.66 cm on the affected side, compared with 1.04 cm on the nonaffected side (p = .01) and demonstrated a decrease in cross-sectional thickness as represented as a percentage of the contralateral, nonaffected side when measured against time from rib fracture (R2 = 0.432). The present case series describes the rib fracture characteristics, ultrasound assessment, and interoperative intercostal nerve stimulation findings of patients with preoperative NCS/EMG-diagnosed intercostal nerve injury after rib fractures. Intercostal nerve damage resulting in rectus abdominis atrophy after rib fractures may be an underrecognized and thus undertreated complication of rib fractures. Preoperative electrodiagnostic testing demonstrates high diagnostic accuracy and can guide surgical planning. Awareness of high-risk fracture patterns may improve clinical decision-making and outcomes in rib fracture management.
Compound muscle action potential (CMAP) recording provides an objective electrophysiological assessment of facial nerve function after injury. In rodent models, vibrissal CMAPs serve as quantitative surrogates of facial nerve integrity; however, practical descriptions of CMAP recording setups using widely available systems remain limited. In this study, we detail a practical and reproducible method for recording vibrissal CMAPs following direct stimulation of the facial nerve trunk in rats, using a BIOPAC-based system. CMAPs were recorded before and after unilateral facial nerve crush injury, followed by transection and epineural repair. Direct nerve trunk stimulation reliably elicited stable CMAP waveforms and supramaximal stimulation produced consistent responses suitable for longitudinal assessment. Baseline CMAP amplitudes were comparable to previously reported values. After facial nerve injury, CMAPs on the injured side were absent at 1 week, reappeared at 2 weeks, and increased further by 4 weeks. Because absolute CMAP amplitudes varied across recording sessions despite intact contralateral nerves, functional recovery was evaluated using left/right amplitude ratios. Single-peak CMAP amplitude was used to minimize waveform variability and stimulus-related artifacts. This method provides a straightforward and accessible approach for the electrophysiological assessment of facial nerve injury and recovery in experimental rodent models.
Lower-extremity nerve reconstruction, most commonly involving the lumbosacral plexus (LSP), sciatic nerve (including common peroneal and posterior tibial nerves), and the femoral nerve, remains one of the most demanding challenges in peripheral nerve surgery, with outcomes primarily determined by injury mechanism, anatomical level, and timing of reconstruction. Over the past 35 years (1987-2022), the Peripheral Nerve Team at the Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan treated 3 patients with LSP injuries, 6 patients with femoral nerve injuries, and 35 patients with sciatic nerve injuries using different surgical techniques, including neurolysis, direct nerve repair, cable grafting, nerve transfer, vascularized nerve grafting, and adjunctive procedures such as functioning free muscle transplantation (FFMT) and tendon transfer. The corresponding surgeons included D.C-C.C., T.N-J.C., and J.C-Y.L. as the senior authors in this paper. Meaningful recovery clustered with early timing and tension-free nerve coaptation; in selected long-segment or scarred beds, well-constructed multistranded or vascularized grafts achieved useful function, yet the superiority of vascularized constructs was not uniform across cases. Delayed exploration and isolated neurolysis generally yielded limited improvement. Although functional recovery declined with increasing graft length, satisfactory results were observed in selected extensive reconstructions using multiple grafts appropriately and, when indicated, FFMT. These observations highlight the complexity of lower-extremity nerve reconstruction and the need for careful surgical planning and long-term follow-up to optimize outcomes after nerve reconstruction in the lower extremities.
Background: The etiology and diagnosis of heel pain are complex and multifactorial, and it has been reported that Baxter's entrapment is responsible for up to 20% of foot disorders. The most conservative treatment of Baxter's entrapment has been the use of custom insoles. Electromyography was considered an effective test to assess muscle activity. The aim of this study was to test the use of insoles of different hardness on muscle activity of the abductor hallucis muscle in subjects with entrapment of the lateral branch of the external plantar nerve. Methods: 18 subjects (7 women and 11 men) diagnosed with nerve entrapment of the first branch of the lateral plantar nerve were recruited. Muscle activity of the adductor hallucis muscle was analyzed with insoles of different hardness in static and dynamic situations using electromyographic evaluation. Results: The statistical analysis did not show statistically significant differences in the muscle activity of the abductor hallucis muscle in the static position, with and without plantar orthoses (p>0.05), in contrast, in dynamic situations statistically significant differences were found between groups (p<0.01). Conclusions: The use of a hard insole decreases the maximum peak muscular activity of the abductor hallucis muscle in subjects with Baxter's nerve entrapment in walking conditions.
Ulnar nerve injuries lead to severe intrinsic hand muscle dysfunction and major impairment of grip, pinch, and quality of life. Distal nerve transfers have been introduced to overcome the limitations of conventional repair and grafting by shortening the regeneration distance and improving reinnervation of intrinsic muscles. Can distal anterior interosseous nerve to deep motor branch of the ulnar nerve (AIN-to-UN-DMB) transfer restore intrinsic hand function and improve patient-reported quality of life in proximal ulnar nerve injuries? Twelve patients with proximal ulnar nerve injuries underwent distal AIN-to-UN-DMB transfer and were prospectively evaluated at 24 months postoperatively. Outcomes included intrinsic muscle strength graded by the BMRC scale, Egawa's sign, dynamometric assessment of grasp and pinch strength, and quality of life measured using the PNSQoL questionnaire. At final follow-up, intrinsic muscle strength improved markedly: 27 muscles achieved M4 and 14 achieved M3 strength, compared with universal M0 preoperatively. Grasp strength increased from a mean of 42.3% to 82.5%, and pinch strength from 37.4% to 80.5% of the contralateral hand. Overall satisfactory functional recovery was achieved in 87.5% of patients. Mean PNSQoL score improved significantly from 47.7 preoperatively to 74.4 postoperatively (p < 0.001), with all patients reaching very good or excellent quality-of-life categories. Distal AIN-to-UN-DMB transfer enables meaningful restoration of intrinsic hand function, substantial gains in grasp and pinch strength, and significant improvement in quality of life, representing an effective reconstructive option for proximal ulnar nerve injuries.
Inclusion body myositis (IBM) is an inflammatory myopathy with an insidious onset, often making diagnosis challenging. Although neuroimaging has recently been included in diagnostic criteria, the role of muscle ultrasound-despite being a rapid and cost-effective tool-in IBM has been less extensively characterized. In this study, we aimed to explore whether qualitative and quantitative muscle ultrasound measures reflect the pattern of muscle involvement in IBM and are associated with magnetic resonance imaging (MRI) findings. Thirteen patients with histologically confirmed IBM underwent clinical evaluation, including the IBM Functional Rating Scale (IBM-FRS) and Medical Research Council (MRC) grading. Qualitative (Heckmatt scale, from 1 to 4) and quantitative (muscle echo-intensity and thickness z-scores) ultrasound assessments were performed on fourteen muscles bilaterally. Lower limb muscle MRI was conducted using T1-weighted (with Mercuri score) and STIR sequences. Correlations between ultrasound parameters and MRI findings were analyzed. Qualitative ultrasound assessment showed increased echogenicity, mainly in flexor digitorum profundus, vastus lateralis, rectus femoris, tibialis anterior, and medial gastrocnemius. Quantitative analysis confirmed elevated echo-intensity in these muscles, with milder involvement of tibialis anterior and lateral gastrocnemius. Both qualitative Heckmatt scores and quantitative muscle echo-intensity scores showed positive associations with MRI T1 Mercuri scores (p < 0.001). In this study, both qualitative and quantitative muscle ultrasound reflected the characteristic pattern of muscle involvement in IBM and showed associations with MRI findings, supporting their utility in describing the pattern and extent of muscle damage.
Sciatic nerve injury causes a loss of skeletal muscle innervation, reduced motor function, and eventual muscle atrophy. Inflammation and increased protein degradation are key factors contributing to muscle atrophy. Inflammation is activated early during muscle atrophy and can be modulated by various factors. However, the precise role of inflammation in denervation-induced muscle atrophy remains unclear. Transcriptome sequencing was used to determine that the inflammatory response occurs early during denervation-induced muscle atrophy. RT-qPCR validation of several inflammatory factors showed rapid upregulation at early stages, followed by gradual downregulation. Weighted gene coexpression network analysis of differentially expressed genes identified gene modules whose expression patterns were correlated with or inversely correlated to the inflammatory phenotype, thereby identifying key regulatory factors. A total of 14 coexpression modules were identified, and expression patterns opposite to those of inflammatory factors were examined to investigate potential regulatory molecules that could inhibit inflammation and protect skeletal muscle. Ankrd2 was identified in the darkorange module, showing no significant change at 36 h postdenervation, followed by gradual upregulation, which was opposite to the expression of inflammatory factors. An Ankrd2-overexpressing lentivirus was injected into the tibialis anterior muscle, and Ankrd2 overexpression was found to significantly alleviate muscle atrophy. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that Ankrd2 overexpression was associated with downregulation of inflammation-related pathways, particularly the NF-κB signaling pathway. Proatrophy genes in both the ubiquitin-proteasome and autophagic-lysosomal systems were also suppressed. The present study suggests that denervation-induced muscle atrophy is alleviated by Ankrd2, potentially through inhibition of inflammation, highlighting its potential as a therapeutic target.
Quadrangular space syndrome (QSS) is a rare condition involving compression of the axillary nerve and/or posterior circumflex humeral artery within the quadrangular space. Neurogenic QSS is caused by entrapment of the axillary nerve due to fibrotic bands, paralabral cysts, trauma, or space-occupying lesions, leading to shoulder pain, weakness, and deltoid atrophy, which is frequently observed in athletes performing overhead activities. A 21-year-old female competitive volleyball player presented with a 5-year history of progressive right arm weakness and shoulder pain, worsened by shoulder activity. The patient's symptoms persisted despite conservative treatments. On examination, she had visible right anterolateral deltoid atrophy and 4/5 weakness with right shoulder forward flexion. Electromyography showed denervation of all 3 deltoid heads with severely decreased motor units, while magnetic resonance imaging demonstrated compression of the right axillary nerve within the quadrangular space and denervation changes of the deltoid muscle. Given the failure of nonsurgical interventions, ongoing symptom progression, and examination findings, axillary nerve decompression was recommended. A posterior surgical approach was used for axillary nerve decompression using microsurgical techniques. The patient was positioned supine; a posterior arm incision was made, and the deltoid muscle and the long head of the triceps brachii were exposed and retracted to access the quadrangular space. The teres major fascia was opened to visualize and divide a compressive fibrotic band, completing the nerve decompression. The surgery was successful, with significant postoperative improvements. The patient began rehabilitation at 4 weeks postoperatively and experienced restored deltoid muscle mass and strength by the 6-month follow-up, and durable relief at 2 years postoperatively. She achieved a full return to sports. Axillary nerve decompression proved effective for treating neurogenic quadrangular space syndrome in this case, especially after conservative management had failed. The procedure preserved shoulder function without the need for additional surgical interventions. Return to sports was achievable without complications by 6 months postoperatively. At 2 years postoperatively, the patient continued to have durable relief. The treatment and outcome in this case were consistent with existing literature on this topic, which is Level 4 evidence in the form of case reports and case series. The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Peripheral nerve injury-induced muscle atrophy shares core pathophysiological features with systemic wasting disorders including cachexia and sarcopenia, yet early molecular triggers remain undefined. This study investigates the pathogenic role of receptor-interacting protein kinase 3 (RIPK3) in denervation atrophy. Sciatic denervation was induced in rats for initial time-course transcriptomics and in mice for genetic and pharmacological studies. Assessments in wild-type and RIPK3-knockout mice included transcriptomics (RNA-seq, qPCR), muscle morphology (wet weight ratio, cross-sectional area), histological inflammation (H&E, CD68 immunofluorescence), mitochondrial function (complex I/V activity, ultrastructure and biogenesis/fission regulators), STRING analysis to identify downstream effectors, validated key effectors NOX2 and NOX4 (qPCR/Western blotting) and associated redox status (DHE staining), and analysis of myofibrillar protein content and proteolytic markers (Western blotting). Confirmatory studies included RIPK3 overexpression in C2C12 myotubes and its pharmacological inhibition (GSK872) in mice. RIPK3 emerged from transcriptomic analysis as an early upregulated mediator in denervated muscle, with protein levels increasing approximately threefold at 36 h post-injury. Genetic ablation of RIPK3 attenuated muscle atrophy, as shown by improved gastrocnemius wet weight ratio (p = 0.0110). This protective effect was directly evidenced by a 40.7% increase in cross-sectional area (p = 0.04). The morphological preservation was accompanied by markedly suppressed expression of key atrophy markers, including MAFbx, MuRF1 and FoxO3a (all p < 0.01), and preserved MHC levels (p = 0.0278). Mechanistically, RIPK3 knockout reduced inflammation, enhanced oxidative phosphorylation (GSEA FDR < 0.001) and partially restored mitochondrial function, evidenced by significantly increased complex I (p = 0.0438) and complex V (p < 0.001) activity, preserved ultrastructure, upregulated PGC-1α and NRF2 (both p < 0.05) and downregulated mitochondrial fission proteins (p-DRP1, MFF, FIS1; all p < 0.01). STRING analysis predicted NOX4 as a key downstream effector, validated by reduced NOX4 protein (-46.6%, p = 0.0366) and a consequent 52.2% decrease in ROS accumulation (p < 0.001). Consistently, RIPK3 overexpression in C2C12 myotubes elevated NOX4 (p = 0.0046) and atrophy markers, whereas pharmacological inhibition of RIPK3 in mice replicated the protective phenotype, increasing muscle wet weight ratio (p = 0.0277) and suppressing NOX4 (p = 0.0398) and proteolytic markers. Denervation activates RIPK3 as a master regulator that drives muscle atrophy via NOX4/ROS-induced mitochondrial dysfunction, sustained inflammation and ubiquitin-proteasome activation. Targeting RIPK3 preserves muscle mass and may offer a novel therapeutic strategy for neurogenic muscle atrophy, with possible implications for related wasting disorders.
Peripheral nerve injuries remain a major clinical challenge, often leading to long-term motor and sensory deficits. Stem cell-based and cell-free approaches, combined with biomaterial scaffolds, have emerged as promising strategies for nerve repair. This study evaluated the regenerative potential of human dental pulp stem cells (hDPSCs), their conditioned medium (hDPSCs-CM), and the combination of hDPSCs with olfactory mucosa mesenchymal stem cell conditioned medium (OM-MSCs-CM) in a rat model of sciatic nerve neurotmesis repaired with a chitosan-based nerve guide conduit (Reaxon®). Twenty-seven rats were allocated into experimental groups, including an uninjured control (contralateral limb), an end-to-end neurorrhaphy surgical control group, and treatment groups repaired with Reaxon® alone or combined with hDPSCs, hDPSCs-CM, or hDPSCs with OM-MSCs-CM suspended in Matrigel®. Following nerve transection, a 9-10 mm sciatic nerve gap was created. Functional recovery was monitored over 20 weeks through motor, nociceptive, behavioral, gait, stereological, histomorphometric, and electrophysiological evaluations. All treatments promoted progressive motor recovery and partial restoration of nociceptive function compared to the untreated condition, although the magnitude of improvement differed among groups. The hDPSCs-CM-treated group (CMDP) showed the most favorable overall outcomes, including the lowest muscle mass loss, higher compound muscle action potential amplitudes, and functional indices approaching control values, indicating enhanced reinnervation and neuromuscular preservation. Histomorphometric and stereological analyses confirmed active regeneration across all groups, characterized by microfasciculation and thinner myelin sheaths typical of regenerating fibers. Despite incomplete recovery, the combination of biological therapies with chitosan conduits provided an effective environment for axonal regrowth and functional improvement. These findings highlight the relevance of CMDP as a potent biological adjunct in peripheral nerve repair and support the development of cell-free, clinically translatable strategies for neuroregeneration.
Interscalene brachial plexus block (ISBPB) combined with supraclavicular nerve block or superficial cervical plexus block has been reported to be a reliable, efficacious anesthesia technique for clavicle fracture surgery. However, several serious adverse events impeded the development of this technique. Herein, we propose a novel nerve block technique-the subclavius muscle plane block (SMPB) combined with supraclavicular nerve block-that selectively targets the sensory nerves innervating the surgical region of the clavicle. We hypothesize that SMPB may achieve non-inferior anesthesia efficacy for clavicle surgery compared to ISBPB when combined with supraclavicular nerve block, with fewer complications. This study is a prospective, single-center, randomized, controlled, non-inferiority trial. A total of 76 patients scheduled for open reduction and internal fixation of clavicle fractures will be divided into two groups at random to receive either SMPB or ISBPB, combined with supraclavicular nerve block. The primary outcome will be to compare the proportion of patients not requiring sufentanil supplementation intraoperatively between the two groups. The secondary outcomes will include the pulmonary function before and 30 min after the block, onset time of anesthesia, block-related complications, conversion rate to general anesthesia, intraoperative sufentanil supplementation, surgery duration, intraoperative hemodynamic adverse events, first onset time of pain, first time to patient-controlled bolus, postoperative sufentanil consumption, Numerical Rating Scale scores for rest and dynamic pain at 3, 6, 12, and 24 h postoperatively, motor block grade at 3, 6, 12, and 24 h postoperatively, postoperative nausea and vomiting, metoclopramide dose, nerve injury, patient satisfaction score, and surgeon satisfaction score. This study explores the SMPB as a novel anesthetic technique for clavicle surgery. Compared to ISBPB, SMPB may offer effective anesthesia while reducing complications regarding limb immobility and phrenic nerve paralysis, thus potentially enhancing patient safety, comfort, and postoperative recovery. Chinese Clinical Trial Register, ChiCTR2500096952. Registered on February 10, 2025.
Objective Almost 70 years ago, Osborne described a fibrous band, Osborne’s ligament, stretching between the humeral and ulnar heads of the flexor carpi ulnaris, which forms the cubital tunnel’s roof. Prior to this account, this ligament had received limited attention in the anatomical literature and had been poorly studied. Therefore, the present anatomical study was performed to better elucidate this structure. Methods thirty adult anatomical donors (60 sides) underwent dissection of the medial aspect of the elbow with a focus on Osborne’s ligament. Identified ligaments were documented, classified, and measured. Additionally, histological evaluation of these structures was performed. Results osborne’s ligaments were identified on 49 sides (81.7%). These were classified as absent (type I; 18.3%), wide and thin and more distally located (type II; 51%), narrow and more proximally located (type III: 39%), coexistent with an anconeus epitrochlearis muscle (type IV; 6%), and absent with only anconeus epitrochlearis muscle (type V; 4.1%). When coexistent with anconeus epitrochlearis muscle (6%), the anconeus epitrochlearis muscle was usually located more proximally, although in some cases, it was in the same plane, especially with larger anconeus epitrochlearis muscles. Conclusions based on our findings, the Osborne’s ligament is not a ligament but is usually made up of aponeurosis/tendon over the proximal flexor carpi ulnaris muscle and can coexist with the anconeus epitrochlearis muscle. This structure comes in various forms, illustrating that this term is not specific to a single structure. Clinical trial number: Not applicable.
After a crush injury in sciatic nerve fibers, dynamic changes in blood circulation and immune-cell mobilization occur during axonal regeneration. High-resolution visualization under near-physiological conditions is crucial for understanding these mechanisms. Conventional histological techniques introduce perfusion- and dehydration-induced artifacts that obscure circulation. We employed the in vivo cryotechnique (IVCT) to visualize blood flow within sciatic nerve fibers and assess temporal changes during regeneration. In uninjured mice, IVCT preserved native tissue architecture with minimal shrinkage compared to perfusion fixation, with superiority quantitatively shown by fractal analysis. In the crush model, hematoxylin-eosin, Luxol fast blue, and immunohistochemical staining of IVCT-prepared, freeze-substituted sections revealed axonal degeneration and regrowth. The close association between regenerating fibers and vascular structures, along with erythrocyte distribution, indicates a morphological link between nerves and blood vessels. Electrophysiological assessment using compound muscle action potentials and functional recovery measured by the sciatic functional index demonstrated restored nerve function at 28 days, consistent with histology. These findings suggest that IVCT is a useful method for analyzing peripheral nerve regeneration and vascular dynamics, thereby highlighting its potential as a novel approach in peripheral nerve research.
Phrenic nerve stimulation is a rare but recognized complication of pacemaker implantation. The unique presentation of singultus in the presence of a pacemaker does not warrant initial concerns for pacemaker dislodgement, however in conjunction with muscle twitching and recent insertion of said pacemaker, lead dislodgement becomes more likely. We describe a 62-year-old male with history of right nephrectomy and recent placement of dual-chamber pacemaker for complete heart block presented seven days post procedure with right pectoralis muscle twitching and persistent singultus. Electrocardiogram showed an atrial-ventricular paced rhythm. Chest radiography revealed interval retraction of the right atrial lead with ventricular lead remaining in place. Device interrogation confirmed atrial lead dislodgement with subsequent phrenic nerve stimulation. The device was reprogrammed to ventricular-only pacing mode (VVIR), resulting in resolution of symptoms, however it was not a permanent solution. The patient was discharged with plans for outpatient lead revision. Atrial lead dislodgement can result in phrenic nerve stimulation and uncommon symptoms such as singultus and twitching of chest muscles. Prompt recognition of the underlying etiology and reprogramming of the pacemaker can alleviate symptoms and guide further management.
Building upon the clinically established platform of acellular nerve allografts (ANAs), we developed an advanced derivative: acellular nerve perineurium (ANP) grafts. These grafts are characterized by their preservation of the native perineurial barrier architecture and a unique extracellular matrix (ECM) composition, distinct from the endoneurial basement membrane. This distinctive ECM profile endows ANPs with significantly enhanced barrier integrity and robust neuroprotective properties. In vitro evaluations confirmed that ANP provides a highly favorable substrate, effectively supporting the adhesion and active proliferation of dorsal root ganglion neurons. In a rat model of sciatic nerve transection, ANP grafts demonstrated remarkable therapeutic efficacy. They markedly inhibited the deposition of chondroitin sulfate proteoglycans (CSPGs) at the repair site, thereby preventing traumatic neuroma formation. Furthermore, ANP treatment resulted in a doubling of regenerated axon density and a significant increase in target muscle action potential amplitude. Behavioral recovery in ANP-treated animals approached the functional levels observed in crush-injury controls. Multiomics analyses provided mechanistic insight, revealing that ANP-mediated repair activates multiple pro-regenerative signaling pathways. These collective findings position ANP grafts as a highly promising and clinically translatable biomaterial strategy for improving functional outcomes in peripheral nerve repair.
BACKGROUND Kennedy disease, also known as spinal and bulbar muscular atrophy (SBMA), is a rare and incurable X-linked neuromuscular disorder mainly affecting men aged 30 to 60 years. Polymyositis can present similarly, but can be excluded by measuring muscle enzymes, performing muscle imaging, and electromyography. This report describes the case of a 52-year-old man with a 10-year history of progressive limb weakness due to Kennedy disease, established by genetic testing. CASE REPORT A 52-year-old man presented with a 10-year history of gradually progressive proximal limb weakness and persistently elevated creatine kinase levels ranging from 808-2300 U/L (normal 39-308 U/L). One year prior to this admission, the limb weakness had worsened, but initial electromyography, neuroimaging, and muscle biopsy showed no specific abnormalities. Despite a trial of immunosuppressive therapy due to suspected polymyositis, there was no clinical improvement. Neurological examination later revealed gynecomastia, proximal muscle atrophy, and bilateral tongue atrophy with tremor. Electromyography showed chronic neurogenic changes and reduced sensory nerve action potentials. Repeat expansion analysis identified a hemizygous pathogenic CAG repeat expansion in exon 1 of the androgen receptor gene using a short-read next-generation sequencing-based repeat detection algorithm (ExpansionHunter), with an estimated repeat number of 51 (range 50-53). At 6-month follow-up, the patient demonstrated mild progression of motor symptoms but remained functionally stable. CONCLUSIONS This report presents a rare case of Kennedy disease, initially diagnosed as polymyositis, and highlights the importance of follow-up with genetic testing when neurological and electromyography investigations are not typical for polymyositis. Early identification of Kennedy disease helps avoid unnecessary immunosuppressive treatments.
Oral and maxillofacial surgeries or trauma (e.g. impacted tooth extraction, jaw fracture or tumor resection) often lead to concurrent peripheral nerve injury and bone defects, while current collagen/gelatin sponges offer limited therapeutic effects. To address this challenge, we developed innovative electrospun scaffolds (MOF2, MOF4 and MOF6) by in situ synthesis of 3,5-dihydroxybenzoic acid/zinc (DHBA/Zn-MOF) hybrids within a gelatin/polycaprolactone matrix. In vitro, Schwann cells treated with material extracts exhibited enhanced migration, regulated myelin-associated genes (Ngf/Pmp22 upregulated, Ncam downregulated) and increased NGF protein expression via the PI3K pathway. Co-cultured PC12 cells showed increased neurite outgrowth, confirming neural repair potential. Osteoblasts exposed to material extracts showed elevated alkaline phosphatase activity, enhanced mineralization and upregulated osteogenic genes (Runx2, Alp and Opg), verifying osteogenic capacity. In vivo, MOF6 scaffolds achieved superior motor function recovery in a rat sciatic nerve crush model (evidenced by increased compound muscle action potentials and reduced gastrocnemius muscle atrophy) and promoted trabecular bone formation in a rat skull defect model (validated by micro-CT and histological analyses). These findings underscore the dual-functional capability of DHBA/Zn-hybrid scaffolds to simultaneously promote nerve repair and bone regeneration, offering a promising therapeutic approach for complex neuro-bone composite injuries in clinical practice.
While the mature gustatory and trigeminal systems are capable of regeneration following surgical nerve transection, transections occurring early in life result in permanent effects on innervated tissues. Converging evidence suggests that facilitators of the innate immune response, such as neutrophils, may contribute to these developmental differences in injury recovery. In the current study, Sprague-Dawley rats underwent transection of the trigeminal lingual nerve (LX) or gustatory chorda tympani nerve (CTX) at either 10, 25, or 65 days of age. Tongues were extracted 12, 24, or 48 h post-surgery, and MPO+ leukocyte (neutrophil) densities in the taste buds and surrounding muscle and epithelium were assessed. The neutrophil response to LX or CTX performed at 25 or 65 days of age was minimal to non-existent at all time points examined. In contrast, we observed a robust neutrophil response on both the ipsilateral and contralateral sides of the tongue starting 12 h after LX or CTX performed at 10 days of age, continuing through 24 h post-surgery, before returning to baseline quantities at 48 h. These results add to growing evidence that differences in the innate immune response may contribute to developmental differences in gustatory and trigeminal system injury recovery.
Nerve transfers have shifted from "salvage" procedures to a primary, biology-based strategy for restoring priority function after severe peripheral nerve injury, particularly brachial plexus injury. In this invited opinion, we summarize the historical roots of nerve transfer surgery and outline the modern rationale for distal coaptation - shortening regeneration distance, bypassing scarred zones, and directing axons toward functionally critical targets while preserving native biomechanics. We discuss practical donor-recipient selection principles (redundancy, axonal capacity, proximity, and synergy) and contrast proximal versus distal transfer concepts within contemporary reconstructive algorithms. Using representative examples, we emphasize how distal transfers can be integrated with grafting, tendon transfers, or free muscle transfer in staged reconstructions. Based on our clinical experience across elbow, shoulder, and hand reinnervation, we highlight consistently high rates of functionally meaningful recovery and substantial improvements in patient-reported quality of life.
The sternocleidomastoid (SCM) muscle flap technique was incorporated into modified radical neck dissection (MRND-SCM flap) to reduce traction injury to the spinal accessory nerve (SAN), improve surgical visualization, protect the carotid artery, and maintain postoperative neck contour. This study aimed to evaluate the feasibility and safety of this approach in patients with N2-N3 head and neck cancer. Thirty-two patients with clinically N2-N3 head and neck cancer underwent MRND-SCM flap at a single tertiary institution between May 2017 and December 2022 (34 total procedures). Surgical outcomes, perioperative complications, and active shoulder range of motion (ROM) - measured using a standard goniometer preoperatively and at 1, 3, and 6 months postoperatively - were analyzed. The operative procedure was successfully completed in all 32 patients. One patient had SCM muscle partial necrosis during the early postoperative period due to wound infection. Neck tightness developed in 5 patients (15.6%). No SCM rupture, severe atrophy, or clavicle fracture occurred. One patient developed a postoperative hematoma requiring reoperation. Shoulder abduction and flexion decreased significantly at 1 and 3 months but recovered to near-baseline by 6 months. External rotation recovered by 3 months. One patient (3.1%) showed shoulder droop on clinical inspection. MRND-SCM flap demonstrates favorable feasibility and safety profiles in this single-institution retrospective series. The technique preserves the SCM muscle, maintains postoperative neck contour, enables en bloc lymph node dissection, and is associated with near-complete shoulder ROM recovery by six months. These findings represent preliminary safety and feasibility signals. Prospective multicenter studies with larger cohorts are warranted to validate these results.