Search Results (1,916)

CLN1 disease, caused by mutations in the PPT1 gene, is a fatal neurodegenerative lysosomal storage disorder. While central nervous system (CNS) pathology is well documented, the impact on peripheral tissues remains unclear. Having previously described severe spinal cord pathology, we investigated whether PPT1 deficiency also impacts the neuromuscular junction (NMJ) and skeletal muscle, and whether early systemic gene therapy can prevent these disease manifestations. NMJ morphology, terminal Schwann cell (tSC) coverage, and skeletal muscle structure were examined in symptomatic and end-stage Ppt1^−/− mice. Neonatal mice received systemic AAV9-hCLN1 gene therapy via intravenous injection. Untreated Ppt1^−/− mice exhibited pronounced NMJ pathology, including progressive tSC loss, apparently reduced innervation, and increased abnormal acetylcholine receptor clustering. In parallel, we observed skeletal muscle atrophy, with decreased myofiber diameter and reduced myonuclear content, despite preserved sciatic nerve morphology. Systemic AAV9-hCLN1 therapy partially prevented or ameliorated these phenotypes, preserving NMJ innervation and muscle fiber structure. These findings identify peripheral NMJ and muscle abnormalities as previously unrecognized features of CLN1 disease and provide proof-of-concept that early systemic gene therapy can mitigate these effects. Our results highlight the systemic nature of CLN1 pathology and support the need for treatments that address both CNS and peripheral targets for comprehensive disease modification. Full article

The demand for refined anaesthetic protocols in ovine experimental surgery has increased due to ethical considerations and the need to improve perioperative stability. This study evaluated the analgesic efficacy of ultrasound-guided combined sciatic and saphenous nerve blocks using two different local anaesthetics in Hair Canarian Sheep undergoing invasive orthopaedic hindlimb surgery. Fifteen clinically healthy sheep were randomly assigned to one of three groups: lidocaine (2%), bupivacaine (0.5%), or control (general anaesthesia alone). Intraoperative physiological parameters, including heart rate, respiratory rate, and arterial blood pressure, were recorded, and postoperative pain was assessed using a modified Melbourne Pain Scale. Sheep receiving locoregional anaesthesia showed significantly lower postoperative pain scores compared with control animals. Intraoperatively, a significant difference between groups was observed only for respiratory rate, with lower values in the bupivacaine group. The bupivacaine group exhibited lower and more stable respiratory rates, with a trend towards lower heart rates during surgery, as well as consistently lower pain scores during the early postoperative period. Lidocaine provided limited intraoperative and postoperative effects compared with the control group. Respiratory rate appeared to be more closely associated with pain scores than other physiological parameters. In conclusion, ultrasound-guided sciatic and saphenous nerve blocks were associated with improved perioperative analgesia in sheep undergoing orthopaedic surgery. The use of bupivacaine was associated with lower respiratory rates intraoperatively and reduced postoperative pain scores, suggesting a potential benefit in perioperative analgesia. Full article

Background: Predicting functional recovery after selective nerve transfer remains challenging. Intraoperative nerve action potential (NAP) recording is widely used to confirm axonal continuity in peripheral nerve surgery; however, its quantitative prognostic value in selective nerve transfer has not been clearly established. This study evaluated whether intraoperative donor fascicle NAP amplitude predicts functional recovery following selective ulnar-to-musculocutaneous nerve transfer (Oberlin procedure) for restoration of elbow flexion. Methods: This retrospective exploratory observational study included 20 patients who underwent selective ulnar-to-musculocutaneous nerve transfer (Oberlin procedure) with standardized intraoperative neurophysiological mapping and quantitative donor fascicle NAP recording. Functional outcome specific to elbow flexion was assessed at last follow-up using the Medical Research Council (MRC) grading system. Time to first electromyographic evidence of biceps reinnervation was recorded. Associations between intraoperative NAP amplitude and functional, temporal, and clinical variables were analyzed using Spearman’s rank correlation coefficient and non-parametric tests. Results: Donor NAP amplitude demonstrated substantial interindividual variability (range 60–400 µV; median 137.5 µV, IQR 87.5–200 µV). No significant associations were observed between NAP amplitude and final MRC grade (ρ = −0.103; p = 0.666), time to electromyographic reinnervation (days: ρ = −0.123; p = 0.617), patient age, or time from injury to surgery. A moderate negative correlation between NAP amplitude and lesion severity was observed but did not reach statistical significance in this small cohort (ρ = −0.419; p = 0.0659). In contrast, shorter time to electromyographic reinnervation was significantly associated with improved final functional outcome (ρ = −0.559; p = 0.013). No patient reported postoperative hand weakness. Conclusions: In this exploratory cohort, intraoperative donor NAP amplitude was not associated with time to electromyographic reinnervation or final elbow flexion strength following selective ulnar-to-musculocutaneous nerve transfer. Although intraoperative NAP mapping remains essential to confirm axonal continuity and conduction viability of the donor fascicle, NAP amplitude did not demonstrate prognostic value in this cohort and should be interpreted cautiously as an isolated predictor of functional recovery, particularly given the limited sample size and exploratory design. These findings suggest that recovery after selective nerve transfer may be influenced by broader biological determinants, including regenerative timing, rather than by isolated intraoperative amplitude metrics. Full article

Chemotherapy-induced peripheral (CIPN) neuropathy is a common dose-limiting side effect affecting roughly 30–40% patients. Dorsal root ganglia (DRG) neurons are one of the main targets of CIPN as chemotherapy drugs may accumulate in DRG neurons. Chemotherapy drugs may induce direct damages on DRG neurons while also activating immune pathways, which results in the releasing of pro-inflammatory cytokines. This cascade may also damage neurons and amplify pain signaling. Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine with prominent immunomodulatory roles. Here, we report that TGF-β1 can promote axonal regeneration on DRG neurons injured by cisplatin via a suppressor of mothers against decapentaplegic (Smad) signaling pathway. To confirm the involvement of canonical TGF-β signaling, we applied the selective TGF-β type I receptor antagonist SB-431542 and performed a gene knockdown of Smad3 and Smad4, assessing their impacts on TGF-β1’s effects. Our results demonstrate that TGF-β1 could significantly enhance axonal regeneration in DRG, largely through a Smad4-dependent pathway, and we propose TGF-β1/Smad4 as a promising molecular target for treating CIPN. Full article

Background: Peripheral nerve stimulation (PNS) is increasingly used in selected patients with neuropathic pain, and many individuals seek supplemental online information to clarify procedural expectations and postoperative care. Large language models such as ChatGPT may provide scalable patient education; however, their performance for PNS-related questions has not been evaluated. This study assessed the reliability, accuracy, and comprehensibility of ChatGPT-5.0 responses to common PNS patient questions. Methods: We conducted a cross-sectional evaluation of ChatGPT-5.0 responses to 21 standardized questions derived through expert consensus, spanning pre-implantation, implantation, and post-implantation domains. Sixteen board-certified interventional pain specialists and a nurse educator independently rated each response using validated scales for reliability (1–6), accuracy (1–3), and comprehensibility (1–3). Descriptive statistics were calculated, and domain-level patterns were examined. Results: Clinician ratings demonstrated generally strong performance across all domains. Mean reliability was 4.7 ± 1.4, mean accuracy 2.6 ± 0.6, and mean comprehensibility 2.8 ± 0.5. Foundational questions addressing mechanisms, expectations, and postoperative care received the highest ratings. Lower ratings were observed for implantation-focused items requiring procedural nuance. No response fell below predefined acceptability thresholds, and sensitivity analyses confirmed that including one partial evaluator did not alter the observed trends. Conclusions: ChatGPT-5.0 generated responses to PNS-related patient questions that clinicians rated as generally reliable, accurate, and understandable, particularly for foundational and postoperative topics. Performance was more variable for procedural questions, underscoring the need for clinician oversight and verification. These findings provide a benchmark of current LLM capabilities and highlight the importance of ongoing evaluation as models evolve and as patients access versions with differing functionalities. Full article

Small fiber neuropathy (SFN) is an early and common manifestation of diabetic polyneuropathy in type 2 diabetes mellitus (T2DM), often presenting with pain, dysesthesia, and autonomic dysfunction. Conventional diagnostic methods primarily assess large nerve fibers and may miss early small fiber damage, while skin biopsy, though considered the reference standard, is invasive. Corneal confocal microscopy (CCM) offers a rapid, noninvasive alternative for visualizing and quantifying small nerve fiber pathology in vivo. This was a monocentric observational study including 80 adults with T2DM (18–75 years), conducted at Alexandrovska Hospital, Sofia. Peripheral neuropathy was evaluated using a modified Neuropathy Disability Score and CCM-derived corneal nerve fiber density (CNFD), length (CNFL), and branching density (CNBD). Autonomic and sudomotor function were assessed by cardiovascular reflex tests and Sudoscan. Additional measures included vibration perception threshold, carotid intima–media thickness, body composition analysis, and laboratory parameters. Autonomic neuropathy was present in 66.7% and peripheral neuropathy in 57.5% of participants. Affected patients were older and had higher BMI and longer diabetes duration; peripheral neuropathy was additionally associated with higher HbA1c. Corneal nerve parameters negatively correlated with diabetes duration, HbA1c, intima–media thickness, and vibration threshold. Patients with diabetic retinopathy showed significantly reduced CNFD and CNFL. ROC analysis demonstrated significant discriminative ability of the HRV index for identifying peripheral neuropathy and of CNFD for detecting sudomotor dysfunction. These findings support CCM as a valuable, noninvasive marker of small fiber damage, closely linked to metabolic control, vascular impairment, and both sensory and autonomic dysfunction in T2DM. Full article

Background/Objectives: Sciatic nerve injuries are among the most common classes of peripheral nerve harm and have a strong impact on quality of life, as well as a significant negative economic impact for patients, society, and governments, since they represent a frequent cause of work-related disabilities and sick leave applications. Following nerve injury, neurons, Schwann, and satellite cells undergo marked changes in phenotype, metabolic activity, neuronal survival, nervous transmission, and an exacerbated activation of the inflammatory response. Leuprolide acetate (LA), a clinically available agonist of gonadotropin-releasing hormone (GnRH), has shown clear neurotrophic properties and is considered a novel potential candidate for treating neural injuries, including sciatic nerve pathologies. This study aimed to analyze the effect of LA treatment on sensory function and dorsal root ganglia (DRG) changes in a rat sciatic nerve full-transection (SNT) model. Methods: Variations in cold and heat sensitivity were assessed using the thermal plate test, while DRG tissue sections were examined for modifications in reactive gliosis by immunofluorescence analysis, and axonal transport using a retrograde tracer. Also, changes in the expression of pro-regenerative genes Stat3, Socs3, Fos, Jun, Atf4, and Limk1 were quantified by qPCR. Results: Our results showed that LA treatment exerted a distinct neurotrophic effect, since it promoted the specific recovery of cold sensitivity, improved axonal transport, regulated the inflammatory response, and modulated the exacerbated expression of pro-regenerative genes in the SNT model. Conclusions: These findings indicate that LA therapy may have the potential to improve sensory recovery in patients with sciatic nerve injuries. Full article

Combined central and peripheral demyelination (CCPD) is a rare neuroimmunological condition involving inflammatory demyelination of both the central nervous system (CNS) and peripheral nervous system (PNS). We report a chronic progressive CCPD case initially diagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP) and treated with conventional CIDP-directed immunotherapies, with subsequent development of multiple sclerosis (MS)-like CNS demyelination. An extensive diagnostic evaluation excluded alternative infectious, metabolic, paraneoplastic, and antibody-mediated etiologies affecting either compartment. In the absence of a unifying pathogenic autoantibody, the combined clinical, radiological, cerebrospinal fluid, and electrophysiological findings support a shared immune-mediated process. Within this framework, B cells are implicated through antibody-independent mechanisms, including antigen presentation, pro-inflammatory cytokine production (e.g., IL-6), and amplification of Th1/Th17-driven inflammation. Interactions between B cells and the complement system via CR1 (CD35) and CR2 (CD21), together with dysfunction of the blood–brain barrier (BBB) and blood–nerve barrier (BNB), may facilitate parallel immune activation across both compartments. In this case, the observed radiological and electrophysiological stabilization under anti-CD20 therapy is consistent with a B-cell-driven pathogenic model in CCPD. Full article

Background/Objectives: Wide Awake Local Anesthesia No Tourniquet (WALANT) and ultrasound-guided peripheral nerve blocks (PNBs) are increasingly used alternatives to general anesthesia for hand and forearm surgery. While WALANT is commonly perceived as a time-efficient and resource-sparing technique, comparative data regarding patient satisfaction, perioperative pain, and time-related outcomes remain inconsistent. This study aimed to compare WALANT and ultrasound-guided supraclavicular peripheral nerve block techniques with respect to patient satisfaction, perioperative pain, time-related parameters, and surgeon-related outcomes in elective hand and forearm extremity surgery. Methods: This prospective comparative observational study included 80 adult patients undergoing elective hand or forearm surgery. Patients received either WALANT or ultrasound-guided supraclavicular brachial plexus block according to patient preference. The primary outcome was overall patient satisfaction assessed within 24 h postoperatively. Secondary outcomes included block performance time, waiting time, total anesthesia-related time, intraoperative and postoperative pain scores, additional sedation requirements, postoperative numbness, willingness to choose the same anesthetic technique again, safety outcomes and surgeon satisfaction. Results: Overall patient satisfaction was significantly higher in the peripheral nerve block group compared with the WALANT group (median [IQR]: 90 [85–100] vs. 80 [70–90], p < 0.0001). Intraoperative and postoperative pain scores were also significantly lower in the peripheral nerve block group. Although block performance time was longer with the peripheral nerve block, waiting time and total anesthesia-related time were significantly shorter compared with WALANT. Surgeon satisfaction and the need for additional intraoperative sedation did not differ significantly between groups. Conclusions: In elective hand and forearm surgery, ultrasound-guided supraclavicular peripheral nerve block was associated with higher patient satisfaction, lower pain scores, and shorter total anesthesia-related time compared with WALANT. Surgical satisfaction scores were similar with both anesthetic techniques. Considering the heterogeneity of clinical settings and procedural requirements, as well as cost and resource utilization considerations, anesthetic technique selection should be individualized. Full article

Background: Granular cell tumors (GCTs) are rare neoplasms that may also involve the musculoskeletal system and peripheral nerves of the extremities. In these locations, their clinical presentation, management, and outcomes remain poorly characterized. Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, MEDLINE, EMBASE, and Scopus were searched for articles published between 1975 and 2025 reporting GCTs arising from the musculoskeletal system or peripheral nerves, with available data on clinical presentation and treatment. Tumor location and size, symptoms, treatment modality, and oncological outcomes (recurrence or metastasis) at the latest follow-up were extracted. Results: Forty articles describing 67 cases were included (50 females, 17 males). Tumors showed benign (47) or atypical (2) behavior in 49 cases and malignant features in 18 cases. The mean largest tumor diameter was 44 mm, and malignant lesions were significantly larger than benign ones. Thirty-one lesions were located in the lower limbs, 25 in the upper limbs, and 11 had central musculoskeletal localizations. Swelling was the most common presenting symptom (92%), followed by pain (40%). Surgical excision was performed in all patients except one, who underwent primary amputation. Adjuvant chemotherapy or radiotherapy was sporadically used in malignant cases (two cases each). Among the malignant cases with reported oncological follow-up, 44% developed distant metastases, and one (5.6%) also experienced local recurrence. Only one benign GCT recurred (2%), whereas all other non-malignant lesions remained CDF (98%). Conclusions: Although rare, GCTs should be considered in the differential diagnosis of musculoskeletal soft-tissue tumors, given their potential for malignant behavior and metastatic spread. Full article

Peripheral nerve injuries pose a significant clinical challenge due to the limited self-repair capacity and the complexity of neural tissue architecture. Tissue engineering strategies applied to the peripheral nerve system aim to restore functional nerve constructs by combining scaffolds, cells, and biochemical cues to recreate the native microenvironment. This work aimed to propose the electrical conductivity as a functional readout of structural and biological remodeling in engineered peripheral nerve scaffolds, along with functional and molecular evaluations. To this end, bioimpedance measurements were combined with equivalent circuit modeling to track state-dependent changes across different levels of tissue organization. Murine sciatic nerves were decellularized and recellularized with neural populations to generate engineered constructs, and their electrical properties were assessed using broadband bioimpedance spectroscopy. Distinct impedance profiles were observed across control, decellularized, and recellularized samples, reflecting structural and functional changes associated with cell removal and repopulation. Furthermore, a multilayer series RC circuit model was implemented to accurately reproduce the measured spectra, enabling the extraction of layer-specific electrical parameters. Analysis of these parameters revealed that decellularization reduces compartmental resistances and increases inter-layer coupling, whereas recellularization restores outer-layer resistances and reduces coupling, consistent with functional tissue organization. Overall, the results demonstrate that bioimpedance provides a readout of the scaffold biological state and cellular integration, and that equivalent circuit modeling offers a quantitative framework to link structural remodeling to electrical function in engineered peripheral nerve tissues. Full article

Background: Mas-related G-protein-coupled receptor b4 (Mrgprb4)-lineage neurons in the peripheral nervous system are a type of C fibers in hairy skin. Our prior work demonstrated that these neurons respond to both noxious and innocuous mechanical and thermal stimuli. Ablating them eliminates the pleasant sensation elicited by gentle pressure on a mouse’s nape. However, their potential role in mitigating pain and pain-related negative emotions in response to somatic stimuli remains unclear. Methods: A CFA-induced chronic pain and anxiety comorbidity model was established in C57BL/6J mice. In vivo calcium imaging of dorsal root ganglia (DRG) neurons in Mrgprb4-GCaMP6s transgenic mice characterized neuronal responses to transcutaneous electrical nerve stimulation (TENS) at the Zusanli (ST36) acupoint. Optogenetic activation (Mrgprb4-ChR2 mice) and viral ablation of Mrgprb4-lineage neurons were employed to evaluate their role in mediating TENS effects on mechanical pain thresholds and anxiety-like behaviors. Results: In vivo calcium imaging revealed that 0.5 mA TENS preferentially activated Mrgprb4-lineage neurons compared to 2.0 mA TENS. In CFA model mice, 0.5 mA TENS at ST36 significantly increased mechanical pain thresholds and reduced anxiety-like behaviors in the open-field test. Optogenetic activation of Mrgprb4-lineage neurons at ST36 replicated these analgesic and anxiolytic effects, demonstrating the sufficiency of these neurons for therapeutic outcomes. Conversely, viral ablation of L3–L5 Mrgprb4-lineage neurons substantially attenuated the therapeutic effects of 0.5 mA TENS for both pain relief and anxiety reduction, indicating their necessity in mediating TENS efficacy. Conclusions: Mrgprb4-lineage neurons serve as critical peripheral mediators of TENS-induced analgesia and anxiolysis. These findings identify a specific neuronal population underlying the therapeutic effects of somatic stimulation at ST36, providing mechanistic insights that may guide optimization of TENS parameters for treating chronic pain and comorbid anxiety in clinical settings. Full article

Satellite glial cells (SGCs) are morphologically unique peripheral glial cells that surround neuronal somas in sensory, sympathetic, and parasympathetic ganglia. Satellite glial cells communicate with neurons that they ensheathe and form a distinct structural and functional unit. Following peripheral nerve injury, satellite glial cells undergo remarkable morphological changes, including gliosis, and help regulate the microenvironment surrounding neuronal somas. The expression of many satellite glial cell markers such as glial fibrillary acidic protein (GFAP) and connexin-43, pro-inflammatory cytokines, and growth factors in satellite glial cells is altered in these cells. Injury responses of satellite glial cells, particularly the activation of peroxisome proliferator-activated receptor α (PPARα), contribute to enhanced axonal regeneration. Targeting satellite glial cells may therefore offer novel therapeutic strategies for the treatment of peripheral nerve injury. Full article

Background/Objectives: Large language models (LLMs) are increasingly used for patient education, yet comparative evidence regarding their accuracy, safety, and ethical performance remains limited, particularly in high-risk fields such as anesthesiology. This study aimed to conduct a multidimensional comparison of five contemporary LLMs in answering common patient questions in anesthesiology. Methods: In this cross-sectional, comparative in silico study, 30 standardized patient questions covering general anesthesia, spinal/epidural anesthesia, and peripheral nerve blocks were submitted to ChatGPT, Gemini, Microsoft Copilot, DeepSeek, and Grok. Responses were independently evaluated under full blinding by five senior anesthesiology professors using a 5-point Likert scale across six domains: accuracy, safety, completeness, understandability, ethics, and overall assessment. Inter-rater reliability was assessed using intraclass correlation coefficients (ICC). Performance differences were analyzed using linear mixed-effects models accounting for question- and evaluator-level variability, with results reported as estimated marginal means. Results: Inter-rater agreement was good to excellent across all domains (ICC > 0.75). Significant model-related differences were observed for overall assessment, accuracy, safety, completeness, and ethics (all p < 0.001), whereas understandability did not differ significantly between models. ChatGPT achieved the highest overall performance, while Gemini demonstrated superior accuracy. Model performance varied across anesthesiology subspecialties, with significant model × topic interactions identified in multiple domains (p < 0.01). Conclusions: LLMs may serve as supportive tools for patient education in anesthesiology; however, their performance varies substantially across models and clinical contexts. Differences in accuracy, safety, and ethical performance highlight the need for cautious, context-aware integration of LLMs into clinical practice rather than their use as substitutes for anesthesiologists’ clinical judgment. Full article

Background: Structural and functional alterations resulting from radial access for cerebral diagnostic catheter angiography might contribute to impaired wrist function. This study aimed to evaluate the impact of the transradial approach for diagnostic cerebral procedures on wrist function, using prospective follow-up assessments. Methods: Wrist function was prospectively assessed by using the Patient-Rated Wrist Evaluation (PRWE) questionnaire at baseline (pre-procedural assessment), as well as at 1-month and 3-month follow-up assessments (PRWE: 0 to 100, with 0 indicating no functional impairment). Association analyses with demographic and clinical parameters were performed using univariate logistic regression models. Results: During the 12-month observation period, 35 patients were enrolled in the study. At baseline, 25 patients (71.4%) reported no wrist impairment, while 10 patients (28.6%) had PRWE scores of up to 51. At the 1-month assessment, seven participants (20%) experienced a worsening in wrist function, reflected by increased PRWE scores. Of these, five patients showed deterioration exceeding the minimum clinically important difference. Another eight participants (22.9%) showed an improvement. A worsening of wrist function between the baseline and 1-month follow-up was not significantly associated with age, sex, prior neurosurgical status, body mass index (BMI), total procedure duration, dose area product, or fluoroscopy time (p > 0.05). At the 3-month follow-up, none of the patients reported any wrist-related impairments. Conclusions: In this exploratory cohort, the use of the transradial approach for cerebral angiography resulted in no wrist-related impairment at the 3-month follow-up. Transient worsening occurred in 20%, including clinically relevant cases, underscoring the need for larger studies with objective outcome measures. Full article