Search Results (9,712)

Charcot–Marie–Tooth (CMT) is a rare, genetic, slowly progressive disorder that affects nerve conduction, particularly in the limbs and, therefore, the muscles. Phenotypes vary, but the impact on quality of life is always present. CMT1A is the most prevalent type. There is no pharmacological cure, so physiotherapy is essential, but nutritional and exercise aspects are rarely considered. In this case report, we demonstrate how, even in this condition, effective results can be achieved with strength training if properly supervised, coordinated with physiotherapy, and combined with an appropriate nutritional plan. Full article

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting toxicity in child, adolescent, and young adult (CAYA) oncology populations. Despite its clinical impact, objective biomarkers for early detection and monitoring remain limited. Neurofilament light chain (NfL), a marker of axonal injury, has emerged as a potential circulating biomarker of CIPN in adults and potentially for CAYAs. This pilot study evaluates the association between NfL and patient-reported CIPN severity in CAYAs. Methods: We conducted a prospective pilot study of 26 patients with acute lymphoblastic leukemia or lymphoma. CIPN was assessed using FACT-GOG/NTx scores. Linear mixed-effects models evaluated associations between NfL and neuropathy over time, adjusting for age and time from baseline. Logistic mixed models assessed the relationship between NfL and clinically significant neuropathy (FACT-GOG/NTx ≤ 40). Results: NfL was significantly associated with worsening neuropathy. A 50-unit increase in NfL corresponded to a 1.1-point decrease in FACT-GOG/NTx score (p < 0.001). Each doubling of NfL was associated with a 0.61-point decrease in FACT-GOG/NTx (p < 0.001). Higher NfL levels increased odds of neuropathy (OR 4.62, p < 0.001). Associations were strongest in leukemia patients and not observed in Hodgkin lymphoma when separately analyzed. Conclusions: This pilot study demonstrates that circulating NfL correlates with patient-reported neuropathy severity, supporting its role as a potential biomarker for CIPN in CAYAs. Differences between leukemia and lymphoma cohorts may reflect treatment-specific neurotoxicity patterns and should be validated in larger prospective studies. Limitations include small sample size, heterogeneity, and limited power for subgroup analyses. If validated, NfL could be incorporated into routine toxicity monitoring to identify patients at highest risk for progressive CIPN, enabling earlier supportive care interventions, referral to rehabilitation services, or enrollment in biomarker-guided prevention and treatment trials before irreversible nerve injury occurs. Full article

Background and Objectives: The hybrid assistive limb (HAL) is a wearable robotic device used for rehabilitation that assists the voluntary movements of the user by detecting muscle action potentials and driving actuators positioned next to the hip and knee joints. Although upper-limb HAL training has been studied for brachial plexus injury (BPI), its electrophysiological influence remains unclear. The purpose of this study was to assess the electrophysiological influences of upper-limb HAL-assisted biofeedback (BF) training during elbow flexion rehabilitation in patients with BPI. Methods: Five patients with BPI (average age, 37.2 years) were enrolled after undergoing elbow flexor reconstruction through intercostal nerve-to-musculocutaneous nerve transfer. All participants received outpatient elbow flexion training with the upper-limb HAL at frequencies ranging from once weekly to once monthly. All patients started upper-limb HAL training when re-innervation was observed, and a biceps brachii muscle strength of grade 1 was achieved. Muscle activity was measured using surface electromyography in five patients during upper-limb HAL training, when the biceps brachii muscle strength was graded as Medical Research Council grades 1 and 2, to compare activity with and without HAL. Results: In five patients, electromyographic activity of the biceps brachii during elbow flexion reached 74.9 ± 22.7% of maximal contraction while using the HAL device, compared with 60.3 ± 16.7% without HAL assistance, indicating significantly greater muscle activation during HAL-assisted movement. Conclusions: Robotic BF training for elbow flexion with the upper-limb HAL may serve as a high-quality electromyographic rehabilitation approach for patients recovering from BPI. Full article

Nerve injuries are frequent complications of complex oral and maxillofacial surgical procedures, particularly following extensive tumor resections. Secretome-based, cell-free therapies derived from mesenchymal stromal cells have emerged as promising regenerative approaches; however, robust manufacturing requires the identification of critical quality attributes (CQAs) that ensure product potency and consistency. The influence of replicative senescence during in vitro expansion on the quality of jaw periosteum-derived mesenchymal stromal cell (JPC) secretomes has not yet been established. This study investigated whether the expansion state of JPCs affects the composition and neuro-supportive potency of their secretomes. Secretomes from four independent JPC donors were collected separately at early and late passages, pooled within each passage-specific preparation, and applied to human induced pluripotent stem cell-derived neurons. Neuronal survival, neurite outgrowth, and neuronal marker expression were assessed as functional readouts. Secretome composition was characterized by quantitative proteomics and enzyme-linked immunosorbent assay (ELISA) of selected senescence-associated secretory phenotype (SASP) factors. Secretomes derived from early-passage JPCs significantly enhanced neuronal survival and neurite outgrowth, whereas late-passage secretomes displayed reduced neuro-supportive activity. Proteomic profiling identified a pronounced shift toward inflammatory and stress-associated signaling, whereas performed ELISAs confirmed senescence-associated remodeling of the secretome, including increased abundance of SASP-associated factors in late-passage preparations. These findings demonstrate that prolonged in vitro expansion profoundly influences both the composition and biological potency of JPC-derived secretomes. Collectively, this study identifies the passage-associated senescence-like phenotype of JPCs as a key determinant of secretome quality and supports its consideration as a critical quality attribute for the manufacturing and standardization of JPC-derived secretome products. Monitoring and controlling the expansion state of JPCs may therefore be essential to ensure the consistency, potency, and clinical translation of secretome-based regenerative therapies. Full article

Background: Anterior ischemic optic neuropathy (AION) is a potentially vision threatening disorder that affects middle-aged and elderly individuals. The pathogenesis of the disease remains incompletely understood. However, the most universally accepted hypothesis suggests that a transient reduction in optic nerve head (ONH) perfusion, secondary to hypovolemia, nocturnal hypotension, or small-vessel disease, results in ischemic infarction of the anterior portion of the optic nerve. Case presentation: We present the case of a 61-year-old male patient with a history of arterial hypertension, type II diabetes mellitus, generalized atheromatosis, femoral bypass and stent implantation for chronic ischemia in his left leg, followed by brachial artery dissection that needed a prompt vascular intervention; he presented visual acuity loss in both eyes (BE), with the left eye (LE) being more affected than the right eye (RE). A complete ophthalmologic check-up was performed, and it revealed best-corrected visual acuity (BCVA) RE 0.5 Snellen, LE light perception, normal intraocular pressure (IOP), BE papillary edema and arteriovenous abnormalities. Visual field (VF) examination revealed RE inferior altitudinal defect and LE preabsolute scotoma. The diagnosis of BE anterior ischemic optic neuropathy and hypertensive retinopathy stage II was formulated. Following the aforementioned surgical procedures meant optimizing the patient’s critical vascular status, subsequent management of NA-AION systemic risk factors, along with implementing important lifestyle changes. No further cardiovascular events occurred, and visual field parameters remained stable at the three-year follow-up. Conclusions: Non-arteritic anterior ischemic optic neuropathy (NA-AION) remains a topic of interest for both ophthalmologists and neurologists worldwide. When confronted with a high-risk cardiovascular patient, a rapid and thorough systemic evaluation may prove beneficial. This management strategy could potentially contribute to maintaining a stable systemic outcome, despite major cardiovascular threats. Full article

Background: Treatment-related peripheral neuropathies are disabling long-term complications of modern cancer therapy. Chemotherapy-induced peripheral neuropathy (CIPN) and radiation-induced peripheral neuropathy (RIPN) can lead to pain, motor deficits, and sensory loss, substantially impairing quality of life in cancer survivors. Surgical decompression has been proposed as a potential therapeutic option in cases of superimposed focal nerve compression due to treatment-related tissue changes, but evidence remains limited. This systematic review aims to evaluate the indications, surgical techniques, and outcomes of microsurgical decompression for cancer treatment-related peripheral neuropathies. Methods: A systematic search was performed in PubMed and Embase up to July 2026. Studies were screened by two independent researchers, and included when reporting outcomes of surgical intervention for chemotherapy-induced or radiation-induced peripheral neuropathy. Data on patient demographics, oncologic diagnosis, surgical indication, technique, and postoperative subjective and functional outcomes were extracted and presented in tables. Results: Fourteen studies met inclusion criteria describing 95 patients and 120 treated nerves. In CIPN, all surgically treated patients experienced pain relief and improvement in two-point discrimination, without reported deterioration. In RIPN, 88.5% of patients improved in pain, 58.8% in sensory function, and 44.4% in motor strength. Neurolysis combined with vascularized flap reconstruction was associated with better outcomes when compared with neurolysis alone. No major surgical complications were reported. Overall evidence quality was low, with small sample sizes and high heterogeneity among methodologies. Conclusions: Microsurgical decompression with or without vascularized flap reconstruction may provide meaningful pain relief and partial functional recovery in selected patients with treatment-related peripheral compression neuropathies refractory to conservative management. Nevertheless, current evidence is restricted to small retrospective series and case reports. Full article

Tissue engineering and regenerative medicine are shifting from passive tissue replacement toward instructive platforms that regulate cellular behavior, immune responses, vascularization, and extracellular matrix remodeling. This review examines recent advances in natural, synthetic, composite, and stimuli-responsive biomaterials, biofabrication and 3D bioprinting, stem and progenitor cell therapies, extracellular vesicles and other cell-free products, immunomodulatory scaffolds, skin organoids and organ-on-a-chip systems, nanotechnology, and artificial intelligence-assisted design. Particular emphasis is placed on plastic, reconstructive, and aesthetic applications, including skin and wound repair, craniofacial bone and cartilage regeneration, peripheral nerve reconstruction, vascularization, and dental and periodontal repair. The review also considers biomodulators and skinboosters as emerging regenerative-aesthetic interventions that aim to improve dermal hydration, fibroblast activity, collagen remodeling, and skin quality rather than provide volume replacement alone. Importantly, these technologies differ substantially in translational maturity, ranging from in vitro and preclinical platforms to early clinical interventions, established clinical products, and commercially available treatments for which durable regenerative efficacy remains incompletely validated. Throughout this review, biological plausibility and preclinical efficacy are therefore distinguished from human clinical evidence, regulatory or established clinical use, and commercial availability. Progress will require standardized characterization, mechanism-linked potency assays, clinically relevant models, and outcome measures that capture functional integration, durability, safety, and aesthetic performance. Full article

Chronic heart failure (CHF) is a growing global health concern characterized, in part, by progressive sympathetic overactivation, which exacerbates this condition. Accumulating evidence identifies oxidative stress as a key driver of sympatho-excitation, mediated by excess reactive oxygen species (ROS) and impaired antioxidant defenses. The redox-sensitive transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) is a central regulator of antioxidant gene expression, but its role in the peripheral sympathetic nervous system, particularly in the stellate ganglia, remains unclear. We hypothesized that Nrf2 signaling is disrupted in the stellate ganglia in CHF and that modulation of Nrf2 alters ROS levels and sympathetic responses. In rats, six weeks post myocardial infarction (MI), the stellate ganglia exhibited increased ROS levels in tyrosine hydroxylase-positive neurons along with reduced Nrf2 protein and mRNA expression; both changes were inversely associated with ejection fraction (EF). To determine the functional role of Nrf2, lentiviral vectors encoding GFP or GFP-Nrf2 were delivered to the stellate ganglia three weeks after MI. Nrf2 upregulation attenuated heart rate responses to stellate stimulation in sham rats but augmented responses in CHF rats. The increase in plasma norepinephrine levels was reduced following stellate stimulation in CHF rats that overexpressed Nrf2, while β1-adrenergic responsiveness to dobutamine was unchanged. This study demonstrates that CHF is associated with increased oxidative stress and reduced Nrf2 expression in the stellate ganglion. Nrf2 overexpression significantly modulated sympathetic regulation, altering heart rate responses and reducing plasma norepinephrine in CHF rats. These findings support the concept that impaired Nrf2 signaling contributes to ganglionic redox imbalance and dysregulated sympathetic nerve activity in CHF. Full article

Background: Management of high-grade carotid artery stenosis with concomitant ipsilateral parotid gland tumor presents a rare and challenging surgical condition. Due to the rarity of this dual pathology, standardized guidelines are lacking. Material and Methods: A retrospective study was conducted between January 2020 and May 2025. Six asymptomatic patients with significant carotid stenosis and coexisting ipsilateral Warthin’s tumor underwent simultaneous eversion CEA (carotid endarterectomy) and partial superficial parotidectomy/extracapsular enucleation via a single modified Blair’s incision. Results: Median follow-up was 43 months (range: 12–60 months). Postoperative and long-term survival at median follow-up was 100%, with a 5-year survival rate of 83.3% (one death at 50 months due to myocardial infarction). Disease-free survival at 5 years was 100% for Warthin’s tumor and 83.3% for carotid stenosis. No perioperative transient ischemic attacks (TIA), strokes, hematomas, salivary fistula or iatrogenic cranial nerve injuries occurred. Conclusions: In patients presenting with high-grade carotid stenosis and concomitant ipsilateral Warthin’s tumor, a simultaneous surgical approach is a feasible strategy. This approach eliminates the need for staged interventions, significantly reducing overall anesthetic risk, surgical burden, and healthcare resource utilization. Full article

Background/Objective: Bartonella henselae, the causative agent of cat-scratch disease (CSD), usually causes a self-limiting zoonotic infection. Osteomyelitis is a rare but increasingly recognized manifestation, particularly in children, and may closely mimic malignant or other infectious bone diseases. We present a case of multifocal pediatric Bartonella henselae osteomyelitis and discuss the associated diagnostic and therapeutic challenges in the context of the current literature. Case presentation: We report the case of a previously healthy 10-year-old girl who presented with a one-month history of fever, fatigue, limping, and progressive thigh and groin pain following cat-scratch exposure. During the course of the illness, she developed unilateral facial nerve palsy and Parinaud oculoglandular syndrome. Initial laboratory investigations demonstrated elevated inflammatory markers and reactive thrombocytosis. Serological testing for Bartonella henselae was positive for both IgM and IgG antibodies, whereas polymerase chain reaction (PCR) testing of both peripheral blood and the bone biopsy specimen was negative. Plain radiographs were unremarkable; however, magnetic resonance imaging (MRI) revealed multifocal lesions involving the right femoral diaphysis, right pubic bone, and left iliac wing, together with focal hepatic and splenic lesions suggestive of disseminated disease. Because of the radiological suspicion of malignancy, a femoral bone biopsy was performed and demonstrated osteomyelitis with necrosis and microabscess formation, without evidence of malignancy. Following targeted antimicrobial therapy, the patient showed rapid clinical and laboratory improvement, with progressive regression of the lesions on follow-up MRI. Conclusions: Bartonella henselae osteomyelitis should be considered in the differential diagnosis of multifocal bone lesions in children, particularly in patients with a history of cat exposure. Because the disease may closely mimic malignancy both clinically and radiologically, establishing the diagnosis requires careful integration of epidemiological, clinical, serological, radiological, molecular, and histopathological findings. Early recognition and appropriate antimicrobial treatment are associated with an excellent prognosis. Full article

Adult optic nerve axon regeneration has traditionally been framed as a problem of limited intrinsic growth capacity in central nervous system neurons. However, growing evidence suggests that intrinsic factors alone cannot account for regenerative failure: restrictive extrinsic environmental factors largely govern optic nerve regeneration, dictating the intrinsic capacity axons can express. In this review, we frame the extrinsic optic nerve environment as a dynamic regenerative niche, in which vascular, immune, glial, matrix, and metabolic compartments are spatially co-localized and temporally coordinated rather than acting as independent barriers. These compartments follow a shared trajectory, broadly protective in the acute phase, then inhibitory once the underlying response fails to resolve, while also actively driving one another, such as reactive astrocytes promoting the matrix remodeling that subsequently restricts axon regrowth. Consequently, the niche’s overall permissiveness for regeneration reflects the aggregate and interdependent state of these compartments rather than the action of any single barrier. This review integrates current evidence on extrinsic barriers, intervention opportunities, and disease-specific variability relevant to RGC axon regeneration after injury. These interventions must incorporate the spatial, temporal, and metabolic factors that shape the goal of functional recovery and vision restoration. Full article

Background/Objectives: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by pathogenic variants in the ATP7B gene. Early diagnosis and appropriate treatment are essential for preventing irreversible complications. This study demonstrated the clinical utility of integrated high-throughput genomic analysis for molecular diagnosis and genetic counseling in a large Thai family affected by WD. Methods: A 32-year-old woman with clinical features suggestive of WD underwent clinical, biochemical, and molecular genetic evaluations, including sequencing of the entire ATP7B gene and SNP microarray. Fluorescent PCR followed by capillary electrophoresis was used for segregation analysis in available family members. SNP microarray analysis and whole-exome sequencing were performed on the proband’s husband to identify pathogenic variants in the ATP7B gene and other disease-associated genes for reproductive risk assessment. Results: The proband presented with hepatic dysfunction, Kayser–Fleischer rings, low serum ceruloplasmin, and a family history of fatal liver disease. She also developed progressive weakness, with nerve conduction findings consistent with axonal sensorimotor polyneuropathy predominantly affecting the lower limbs. Sequencing identified a novel homozygous 28-bp splice-junction deletion, c.4022-24_4025del, which disrupted the canonical splice acceptor site at the intron 19/exon 20 boundary and was classified as pathogenic variant. Segregation analysis confirmed carrier status in the proband’s father and identified heterozygous carrier or homozygous wild-type status among her living siblings. SNP microarray analysis revealed a 46.7 Mb copy-neutral long contiguous stretch of homozygosity (CN-LCSH) encompassing ATP7B, with CN-LCSH regions accounting for 2.046% of the total autosomal genome. These findings potentially reflected segmental uniparental isodisomy or identity by descent, while the overall homozygosity pattern did not support recent consanguinity. Combined genomic analyses of the proband’s husband revealed no pathogenic or likely pathogenic ATP7B variants. Based on the available testing, all offspring are expected to be heterozygous carriers, and the risk of an affected child is considered very low. Conclusions: This study highlights the value of integrated genomic analysis for molecular diagnosis, cascade testing, and reproductive risk counseling. Further functional studies should be conducted to validate their pathogenicity. Full article

Addressing the current issues of the uncertain primary frequency bands and the difficulty in directly measuring the spectral characteristics of neural electromagnetic signals transmitted within nerve fibers, this study investigates the spectral and time-domain properties of the neural electromagnetic signals through finite element simulations, using the influence of the node of Ranvier on nerve conduction velocity as a breakthrough point, and develops a coaxial transmission line impedance transformation model. The research results demonstrate that the primary signals capable of effective transmission within nerve fibers may reside in the terahertz (THz) band. They also show that the node of Ranvier essentially functions by regulating its geometric length to achieve impedance matching between the node and the myelin sheath, thereby reaching the optimal efficiency for signal coupling. The above finding not only explains the mechanism underlying the non-monotonic variation in neural conduction velocity with the length of the node of Ranvier, but also provides the latest perspective for understanding the relationship and differences between transmembrane action potentials that accompany the generation of neural signals and information transmission carriers—electromagnetic signals. It may also provide a theoretical supplement to the understanding of signal frequency–timing issues in neural encoding. Full article

Background: Isolated sphenoid sinus disease (ISSD) in children is an uncommon but clinically significant condition that may present primarily with neurological or neuro-ophthalmological symptoms rather than typical sinonasal complaints. Owing to the anatomical proximity of the sphenoid sinus to the optic nerves, cavernous sinus, and multiple cranial nerves, even localized sphenoid pathology may produce symptoms that mimic primary neurological, neuro-ophthalmological, or headache disorders, contributing to diagnostic delay. Objective: To characterize the spectrum and frequency of neurological and neuro-ophthalmological manifestations, diagnostic pathways, treatment strategies, and reported clinical outcomes in pediatric ISSD, with particular emphasis on diagnostic delay and persistent neurological sequelae. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed and Web of Science were searched from database inception to 3 January 2026. Observational studies reporting pediatric patients aged ≤18 years with radiologically confirmed ISSD were included. Single-patient case reports, reviews, and studies without extractable pediatric data were excluded. Owing to substantial clinical and methodological heterogeneity, findings were synthesized descriptively. Risk of bias was assessed using Joanna Briggs Institute (JBI) critical appraisal tools. Results: Eleven studies comprising 136 pediatric patients were included. Most cases were inflammatory lesions (n = 121, 89%), followed by mucoceles (n = 10, 7.3%) and tumors (n = 5, 3.7%). Headache was the most frequent neurological manifestation reported in 129 patients (94.9%). Ocular manifestations were present in 33/136 patients (24.2%), whereas otolaryngological symptoms were reported in 25/134 patients (18.7%). Cranial nerve involvement was documented in 10 out of 54 patients with available data (19%), most commonly affecting cranial nerves III, V, VI, and VII. Among 79 reported initial diagnoses, primary headache disorders were the most common (49.4%), whereas sphenoid sinusitis was correctly identified in only 20.3%. Diagnosis was established using CT and/or MRI in all included cases. Antibiotic therapy was the most common treatment for inflammatory lesions, while all patients with mucoceles and tumors underwent surgical management. Full recovery was reported in 81% of inflammatory cases and in all patients with mucoceles, although follow-up reporting was heterogeneous. Conclusions: Pediatric ISSD frequently presents with neurological and neuro-ophthalmological manifestations, whereas sinonasal symptoms may be absent or subtle. Persistent or atypical neurological symptoms, particularly headache accompanied by ocular symptoms or cranial nerve deficits, should prompt consideration of sphenoid sinus pathology and early cross-sectional imaging. Full article

Background/Objectives: Ultrasound-guided flexor pollicis longus (FPL) injection is limited by the muscle’s deep location and its proximity to the cephalic vein (CV) and superficial branch of the radial nerve (SBRN). We aimed to identify the wrist and forearm posture producing the largest measured corridor width and target exposure. Methods: This prospective single-center study evaluated 51 forearms from 27 healthy adult volunteers with full range of motion, using transverse ultrasound of the distal volar forearm in six standardized positions. Two corridors were measured: CV-to-SBRN (L₁, Approach A) and CV-to-radial-cortex apex (L₂, Approach B), with FPL exposure height (F). Results: L₂ was present in all limbs and was wider with forearm supination than in neutral (supination [SUP], +2.36 mm; flexion plus supination [F+SUP], +2.05 mm; extension plus supination [E+SUP], +2.66 mm; each p < 0.001), an ~40% increase; the three supination postures did not differ. F increased across the same postures and was greatest in E+SUP (+2.32 mm), which did not differ from SUP. L₁ was absent in 12–28% of limbs and, where present, was narrower with supination (both p < 0.001). Conclusions: In healthy adults, forearm supination widened the safety corridor and increased target exposure. Applicability to spasticity requires confirmation. Full article