Articles published on Peripheral Nerve Disorders
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- Research Article
- 10.1016/j.jhsg.2025.100829
- Jan 1, 2026
- Journal of hand surgery global online
- Thomas J Mcquillan + 5 more
Trends in Epidemiology and Reimbursement for Nerve Exploration and Reconstruction After Brachial Plexus Injury in the United States From 2009 to 2019.
- Research Article
- 10.1007/s00415-025-13566-3
- Dec 19, 2025
- Journal of neurology
- Cullen O'Gorman
Weight loss can cause or exacerbate peripheral nerve disorders, including peripheral neuropathy and entrapments. Novel antihyperglycaemic agents, including glucagon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors, may cause weight loss in addition to their effects on glucose levels. Retrospective cohort review from 2020 to 2024 of adult patients undergoing electrodiagnostic evaluation for suspected peripheral nerve dysfunction. Cases were included if there was clinical and/or electrodiagnostic confirmation of peripheral nerve disorder with temporal association (onset < 12months) to use of GLP1R agonists, SGLT2 inhibitors, or dipeptidyl peptidase-4 inhibitors. Five cases are described (78 M with femoral and fibular neuropathy, 58 F with fibular neuropathy, 85 M with fibular neuropathy, 48 M with median nerve entrapments and sensory peripheral neuropathy, 45 M with median and ulnar nerve entrapments and sensory peripheral neuropathy) all temporally associated with weight loss and use of GLP1R agonists or SGLT2 inhibitors. Neuropathy may develop following rapid weight loss or normalization of hyperglycaemia during treatment with GLP1R agonists or SGLT2 inhibitors. The underlying pathogenesis is unclear, but is unlikely due to direct effect of these medications on peripheral nerves. Caution is recommended and further work to establish safe targets for HbA1c and weight loss is needed.
- Research Article
- 10.3343/alm.2025.0534
- Dec 19, 2025
- Annals of laboratory medicine
- Alexandre Jentzer + 10 more
Autoimmune nodopathy (AN) is a disabling peripheral nerve disorder mediated by four pathogenic autoantibodies targeting the node of Ranvier: anti-neurofascin-155 (Nfasc155); anti-Nfasc155 and Nfasc186 (PanNfasc); anti-contactin-1; and anti-contactin-associated protein 1 autoantibodies. Several autoantibody detection assays exist; however, which assay yields the best performance remains unclear. We evaluated the performance of five diagnostic assays individually and in combinations to identify a gold standard assay for diagnosing AN and improve diagnostic accuracy. Sera from 290 individuals from a European cohort, including healthy controls and patients with Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, monoclonal gammopathy, Charcot-Marie-Tooth disease, and AN were tested using five diagnostic assays for AN: ImmunoDOT (D-tek, Mons, Belgium); ELISA; an in-house cell-based assay (CBA); a commercial CBA (Euroimmun, Bussy-Saint-Martin, France); and peripheral nerve immunohistochemistry (IHC). The sensitivity (Se) and specificity (Sp) of the individual assays and their combinations were estimated using Bayesian latent class analysis. The overall Se was 84% (95% credibility interval [CI], 79-88) for ImmunoDOT, 86% (81-90) for ELISA, 96% (93-98) for the in-house CBA, 92% (89-96) for the commercial CBA, and 91% (87-94) for IHC. For all assays, the overall Sp was ≥ 97%. Among the tested assays, in-house CBA showed the best performance, with the highest Se and Sp. The assay combinations demonstrated excellent analytical performance (Se ≥ 91% and Sp ≥ 98%). Inter-laboratory validation revealed excellent repeatability, with a Gwet's agreement coefficient of >0.94 for most assays. Our research suggests that combining two assays, CBA and ImmunoDOT enhances the accuracy of AN diagnosis. This approach can facilitate the establishment of standardized assays for AN diagnosis and aid in the better differentiation of AN from other similar pathologies.
- Research Article
- 10.1002/mus.70108
- Dec 14, 2025
- Muscle & nerve
- Chaichana Sinthuwong + 1 more
Radial mononeuropathy is a common peripheral nerve disorder, but comprehensive clinical or electrodiagnostic (EDX) studies remain limited. This study aims to analyze the clinical features, etiologies, and EDX characteristics of radial mononeuropathy. A retrospective cohort study was conducted on 177 patients (178 lesions) with motor-involved radial mononeuropathy. Lesions were classified by location and etiology into four subgroups: traumatic and nontraumatic, in arm or forearm. Demographics, clinical presentations, and etiologies were compared across subgroups. EDX findings were analyzed, particularly comparing traumatic and nontraumatic arm lesions. Motor nerve fiber involvement was assessed in traumatic and nontraumatic compressive arm lesions. Most patients had radial mononeuropathy at the arm level, presenting with hyperacute/acute weakness and sensory loss. Common causes included nerve compression (40%) and humeral fractures (18%), while etiologies such as multifocal motor neuropathy and neuralgic amyotrophy were rare. EDX showed motor conduction block (CB) mostly across the spiral groove (67%) but sometimes distally (28%). Preserved sensory responses and demyelinating EDX findings dominated in nontraumatic arm lesions. Extensor indicis proprius (EIP), extensor digitorum communis (EDC), and brachioradialis muscles were most frequently affected. Triceps involvement occurred in 22%-49% of arm lesions. Twenty percent of nontraumatic compressive arm lesions with motor conduction block demonstrated triceps involvement. Radial mononeuropathy is most commonly caused by nerve compression and humeral fracture. Demyelinating features are strongly associated with nontraumatic lesions. Recording radial motor responses from EIP and EDC improves motor CB detection and localization. Triceps involvement does not always exclude compressive lesions at the spiral groove.
- Research Article
- 10.1136/bmjment-2025-301923
- Nov 4, 2025
- BMJ Mental Health
- Ella Burchill + 6 more
BackgroundA higher prevalence of neurological conditions has been found in schizophrenia, bipolar disorder and other psychotic illnesses compared to the general population. We aimed to understand the cumulative prevalence of 15 neurological conditions in people with severe mental illness (SMI) from 5 years before to 5 years after their SMI diagnosis.MethodsWe identified patients with SMI, aged 18–100 years from 1 Jan 2000 to 31 Dec 2018, from the UK Clinical Practice Research Datalink. Each SMI patient was matched 1:4 to individuals without SMI. The cumulative prevalence of 15 neurological conditions was recorded at 5, 3 and 1 years prior to SMI diagnosis; at SMI diagnosis; and 1, 3 and 5 years after SMI diagnosis. Prevalences were compared with logistic regression.ResultsWe identified 68 789 patients with SMI and 274 827 comparators. Of 15 neurological conditions, 13 (multiple sclerosis, cerebrovascular disease, dementia, ataxic disorders, epilepsy, Parkinson’s disease, other parkinsonism, paralysis, other movement disorders, cerebrospinal fluid disorders, cerebral palsy, disorders of nerve root, plexus or peripheral nerves and autonomic disorders) were more prevalent in SMI compared with comparators at the time of SMI diagnosis. Dementia (OR: 4.22; 95% CI 3.88 to 4.58), epilepsy (OR: 3.01; 95% CI 2.83 to 3.19) and Parkinson’s disease (OR: 3.97; 95% CI 3.45 to 4.57) were particularly elevated at 5 years post-SMI diagnosis.ConclusionsMany neurological conditions have higher prevalence in the SMI cohort compared with those without SMI. The different prevalence patterns observed in our study highlight the need to establish the causal pathways between specific SMI and neurological disease diagnoses.
- Research Article
- 10.35451/mdw70b38
- Oct 31, 2025
- JURNAL KEPERAWATAN DAN FISIOTERAPI (JKF)
- Sabirin Berampu + 2 more
Carpal Tunnel Syndrome (CTS) is a peripheral nerve disorder that occurs in the hands and wrists which is characterized by complaints of pain, tingling, numbness and even in severe cases there will be muscle weakness and atrophy of the hand muscles. One of the non-pharmacological or conventional treatments for CTS cases is Transcutaneous Electrical Nerve Stimulation (TENS) and Median Nerve Mobilization. TENS and Median Nerve Mobilization can reduce pain complaints in various neuromuscular cases including CTS. The purpose of the study was to determine the effect of TENS and Median Nerve Mobilization on Pain Reduction in CTS Patients in 2025. Research Methods: type of research was a Quasi Experiment with a Purposive Sampling approach technique. The study population of CTS sufferers was 35 people with a sample size of 15 people. The Action Dose was given 3 times per week for 2 weeks or 6 training sessions. The measuring instrument used was the Visual Analog Scale (VAS). Data Analysis Method: Primary Questionnaire Data was Recapitulated and entered into the SPSS Application and Data Normality Test was carried out with Shapiro-Wilk and Wilcoxon Sign Rank Test with a confidence level of 95%. The results of this study obtained the Normality Value of VAS Pretest with a Significance value of 0.015 and Posttest Significance Value of 0.009 with Interpretation of Non-Normally Distributed Data. And the Results of the Wilcoxon Sign Rank Test obtained a P (Value) of 0.001. And the Average Value of VAS Pretest was 6.4 points, Posttest 2.13 points and the average difference value was 4.27 points. The conclusion of this study is that there is a Difference in the Average Value of Pretest and Posttest Pain After being given TENS and Median Nerve Mobilization Physiotherapy interventions so that it can also be concluded that there is an Effect of Transcutaneous Electrical Nerve Stimulation (TENS) and Median Nerve Mobilization on reducing pain in CTS Patients in 2025.
- Research Article
1
- 10.1017/cjn.2025.10416
- Sep 2, 2025
- The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
- Adnan Almasri + 2 more
Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated peripheral nerve disorders. Treatment typically involves immunoglobulin therapy, with both intravenous (IVIG) and subcutaneous (SCIG) routes being used. Although multiple studies have determined that these therapies are effective and comparable, a comprehensive assessment of quality of life (QoL) has not been systematically reviewed. This review aims to evaluate QoL in patients with MMN and CIDP who are treated with SCIG, including those who have made the transition from IVIG to SCIG. We conducted a comprehensive search of electronic databases for studies that measured QoL outcomes in MMN and CIDP patients receiving SCIG. The primary outcome was the change in QoL scores as measured by validated tools compared with baseline values collected during IVIG treatment. Secondary outcomes included adverse effects, treatment satisfaction and functional status. Our review suggests that SCIG may offer comparable QoL outcomes to IVIG with potential benefits in self-administration and reduced systemic adverse effects. This review provides evidence-based insights into the comparative effectiveness of SCIG and IVIG in improving QoL for MMN and CIDP patients. Future research should aim to standardize QoL assessment tools and include larger, long-term studies to better capture the nuanced benefits of SCIG.
- Research Article
- 10.1016/j.neuron.2025.04.006
- Aug 1, 2025
- Neuron
- Alessio Silva + 4 more
Lipid metabolism alterations in peripheral neuropathies.
- Research Article
- 10.33920/med-01-2507-10
- Jul 8, 2025
- Vestnik nevrologii, psihiatrii i nejrohirurgii (Bulletin of Neurology, Psychiatry and Neurosurgery)
- A A Skripnikova
Neuralgias in military personnel represent a significant medical and social issue, as neuropathic pain considerably reduces combat readiness and quality of life [10]. This article summarizes modern approaches to the diagnosis, treatment, and prevention of various types of neuralgia (trigeminal, postherpetic, occipital, intercostal, sciatica, etc.) among military service members. Objective: To assess the clinical characteristics of neuralgias among personnel of the Military Educational and Scientific Center of the Air Force «Air Force Academy named after Professor N. E. Zhukovsky and Y. A. Gagarin,» analyze the effectiveness of current treatment methods, and propose directions for improving medical care in the Armed Forces of the Russian Federation. Materials and Methods: A retrospective analysis was conducted on 120 cases of neuralgia in military personnel (mean age 37.4±8.2 years) over the period 2018–2023. The type of neuralgia, diagnostic procedures, treatment methods (pharmacological, physiotherapeutic, invasive), therapy outcomes, and preventive measures were evaluated. Results: Sciatica (33.3 %) and occipital neuralgia (20.8 %) were the most common, while trigeminal (12.5 %) and postherpetic neuralgia (8.3 %) were less frequent (see Table 1). Chronic pain (>3 months) was noted in 30 % of cases. Diagnosis relied on neurological examination and modern neuroimaging techniques (MRI/CT), enabling the detection of vascular compression or secondary causes, especially in trigeminal neuralgia [6]. First-line therapy (antiepileptics, antidepressants) resulted in complete remission of pain in 67 % of patients, partial improvement in 29 %, and no effect in only 4 % of cases (see Figure 1). Additional use of multimodal therapy — including physiotherapy, nerve blocks, and neurosurgical interventions — allowed for successful management of resistant cases. Discussion: The findings align with literature data on the prevalence of neuropathic pain (7–10 % of the population) and the high incidence of postherpetic neuralgia among peripheral nerve disorders in individuals over 50 years of age [1]. In military personnel, neuralgias are often caused by physical overexertion, injuries, hypothermia, and infections. Modern diagnostics focus on the precise identification of the affected nerve and etiological factors using MRI, electrophysiological studies, and diagnostic nerve blocks. Optimization of treatment includes the administration of evidence-based first-line drugs (carbamazepine, gabapentinoids, amitriptyline, duloxetine), early use of adjunctive methods (lidocaine patches, capsaicin for localized forms [1], botulinum toxin for refractory facial pain), and targeted surgical treatments (microvascular decompression for trigeminal root compression, radiofrequency rhizotomy, etc.). Prevention measures include vaccination (e.g., against Varicella Zoster virus to prevent shingles and postherpetic neuralgia [10]), regular medical examinations, health education aimed at mitigating risk factors (hypothermia, overexertion), and the development of ergonomic military gear to prevent compression neuropathies. Conclusion: The implementation of modern approaches to the diagnosis and treatment of neuralgias within the Armed Forces ensures high medical care effectiveness: over 90 % of affected military personnel return to active duty after treatment. Prospective improvements include establishing specialized «pain» centers in military hospitals, developing departmental clinical guidelines for the treatment of europathic pain, training medical staff in early detection and multidisciplinary management of neuralgias, and further exploring new treatment modalities (gene therapy, neuromodulation) for patients with refractory pain.
- Research Article
- 10.5812/thrita-163516
- Jun 30, 2025
- Thrita
- Farnaz Alidaee + 4 more
Background: Carpal tunnel syndrome (CTS) is one of the most common peripheral nerve disorders in the world, occurring in 4% to 5% of the general population. Conservative treatments, including medications, splinting, corticosteroid injections, or physical therapy, are pragmatic choices for CTS. Statins, endowed with neuroprotective and anti-inflammatory activities, have been suggested as a potential treatment for neuropathies. Objectives: The objective of this study was to assess the effects of rosuvastatin for symptomatic relief and to improve the electrodiagnostic parameters in patients with CTS. Methods: In the present double-blind, placebo-controlled randomized clinical trial, 67 mild to moderate CTS patients, referred to the Booali Sina Hospital Electromyography Clinic in Qazvin, were assessed. Patients were randomized to the intervention group (rosuvastatin 40 mg/daily, n = 32) or to the placebo group (n = 35). Electrodiagnostic and clinical parameters were measured at baseline and 3 months after the treatment. The data were processed using the SPSS statistical software. Results: The mean age in the intervention group was 52.47 ± 10.63 years, and 42.74 ± 9.66 years in the control group. Most participants were female (87.5% in the intervention group vs. 85.7% in the control group). After 3 months, EMG/nerve conduction velocity (NCV) parameters, AST, and LDL levels significantly improved in the rosuvastatin group (all P < 0.05; except right median sensory peak latency). Conclusions: The results imply that a statin like rosuvastatin could promote neurological recovery in patients with CTS, possibly due to its anti-inflammatory and protective effects. This treatment, which is non-invasive, might decrease the demand for invasive treatments such as surgery, thus minimizing the burden of surgical complications and possibly increasing the quality of life for the patients.
- Research Article
- 10.1158/1557-3265.sabcs24-p4-04-31
- Jun 13, 2025
- Clinical Cancer Research
- Jian Zhang + 1 more
Abstract Background: Triple-negative (negative for human epidermal growth factor receptor 2 [HER2] and estrogen and progesterone receptors) breast cancer (TNBC) is the breast cancer subtype with the worst prognosis. It represents approximately 15% -20% of all breast cancer cases. BRCA 1 and /or BRAC 2 mutation accounts for about 15% of all TNBC and remains poor outcomes for such patients. TORCHLIGHT trial is a randomized, double-blinded, phase 3 study assesses the efficacy and safety of toripalimab (programmed cell death-1 inhibitor) combined with nab-paclitaxel (nab-P) as a first-line treatment for patients diagnosed with metastatic or recurrent TNBC. The (progression-free survival) PFS and (overall survival) OS analysis, showed a significant improvement in PD-L1 positive (CPS ≥ 1) tumors. Phase III OlympiAD study has established the efficacy of Poly ADP-ribose polymerase inhibitors (PARPi) olaparib in patients with germline BRCA gene mutation (gBRCAm) and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer. Mefuparib hydrochloride (CVL218) is a second generation of PARPi with low hematological toxicity and the ability to cross the blood-brain barrier. The major purpose of this study is to explore the RP2D, efficacy and safety of CVL218 combined with PD-1 inhibitors and paclitaxel nanoparticle albumin-bound in patients with TNBC who have failed previous first-line treatment. The second endpoint of this study is to analyze the efficacy of each subgroup according to PD-L1 expression and HRD (Homologous Recombination Deficiency) mutation status. Methods: This open- labeled, phase Ib/II clinical study was conducted in China. In phase Ib, the “3+3” principle is used to explore the RP2D of CVL218. Two dose escalation of CVL218 were preset, which are 500mg twice daily (BID) and 700mg BID. CVL218 administered orally in combination with toripalimab 240 mg on Day 1 of every 21-day cycle and paclitaxel nanoparticle albumin-bound 125 mg/m2 on Day 1 of every 21-day cycle. The first cycle (21 days) after administration was also defined as the DLT (dose-limiting toxicity) observation period. At last, no DLT was observed in the 3 evaluable subjects in the CVL218 500 mg BID dose group, and DLT was observed in 2 evaluable subjects in the 700 mg BID dose group, including creatinine increased and aspartate aminotransferase, Alanine aminotransferase increased. Therefore, the RP2D was determined as 500 mg BID. Patients in phase II cohort A were advanced TNBC with either CPS ≥ 1 or HRD gene pathogenic variants. All these patients received CVL218 (500mg BID) + toripalimab (240 mg) + paclitaxel nanoparticle albumin-bound (125 mg/m2, ). Results: From July 2023 to 15 July 2024 data, a total of 6 subjects were enrolled in Phase Ib and 5 subjects were enrolled in Phase II. The median age of the 11 subjects was 55.2 years. In phase Ib, The RP2D of CVL218 was identified as 500 mg BID. The preliminary efficacy was perfomed every 6 weeks in the first half a year and then once every 12 weeks thereafter in both phase I and II according to RECISTv 1.1. Among 11 patients, ORR (Objective Respond Rate) was 72.7% (8 PR, 2 SD), and DCR (Disease Control Rate) was 90.9%. The most common Grade 3 or higher treatment-related AEs (TRAEs) were hepatic function injury (2.6%), adynamia (1.8%), creatinine increased (0.8%), neutrophils decreased (0.8%), white blood cell decreased (0.8%), exanthema (0.8%), and peripheral sensory nerve disorder (0.8%), No Grade 5 TRAE. A total of 9 treatment-related SAEs in 6 patients (54.5%) were observed, including 2 aspartate aminotransferase increased, 2 alanine aminotransferase increased, 1 creatinine increased, 1 liver function injury, 1 adynamia, 1 neutrophils decreased, 1 fever, and 1 ventricular premature beats. All these SAEs recovered after symptomatic treatment. Conclusion: Mefuparib Hydrochloride(CVL218) combined with PD-1 and chemotherapy appears to be well tolerated and has preliminary efficacy in TNBC patients. In this phase II study, stratified analyses will be conducted for PD-L1 expression and HRD status. In patients with BRCA 1 and /or BRAC 2 mutation TNBC, this CVL218 combination therapy is expected to further break through the clinical treatment effect. Citation Format: Jian Zhang, Rujiao Liu. A phase Ib/II study of PARPi Mefuparib Hydrochloride (CVL218) in combination with PD-1 inhibitor plus chemotherapy in metastatic or recurrent triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-04-31.
- Research Article
- 10.3171/2025.4.jns243272
- Jun 1, 2025
- Journal of neurosurgery
- Syed I Khalid + 5 more
The aim of this study was to evaluate milestone progression across 6 Accreditation Council for Graduate Medical Education (ACGME) core competencies and 20 subcompetencies among neurosurgery residents, focusing on the attainment of level 4 proficiency by the final postgraduate year (PGY 7), and to identify patterns of co-occurring deficiencies. A retrospective cohort analysis was conducted using national ACGME Milestone data from 2478 neurosurgery residents across 120 programs in the United States, covering 2018 to June 2022 evaluations. Semiannual milestone scores were analyzed using mean, standard deviation, median, and interquartile range. The proportion of residents not achieving level 4 by PGY 7 was assessed, and co-occurring deficiencies were identified through pairwise analysis and the variance-to-mean ratio (VMR). Residents demonstrated significant progression from PGY 1 to PGY 7, with mean scores increasing from 1.2-1.7 in PGY 1 to 4.20-4.36 by PGY 7. By PGY 7, 445 of 997 residents (44.6%) had not achieved level 4 in at least one subcompetency. Patient Care (PC) had the highest proportion below level 4 (35.5%), particularly in specialized areas such as Surgical Treatment of Epilepsy and Movement Disorders (mean 4.08 ± 0.48) and Pain and Peripheral Nerve Disorders (mean 4.05 ± 0.49). Pairwise analysis revealed co-occurrences among specialized PC subcompetencies and between Reflective Practice and technical competencies. VMR analysis showed substantial variability in subcompetency attainment across programs. Neurosurgery residents show robust milestone progression, yet gaps persist in specialized clinical skills and self-assessment practices, often aligning with subspecialties where fellowship training is common. Residency programs might need to enhance exposure or adjust competency expectations. Integrated educational strategies, including targeted interventions and specialized procedural training, are recommended to ensure all residents achieve level 4 competency, preparing them for independent practice.
- Research Article
- 10.1200/jco.2025.43.16_suppl.3106
- Jun 1, 2025
- Journal of Clinical Oncology
- Bo Yang + 16 more
3106 Background: AXL is a member of the TAM family activated by the high-affinity ligand Gas6. The Gas6/AXL signaling pathway plays a critical role in drug resistance, tumor proliferation, metastasis, invasion, epithelial-mesenchymal transition and immune regulation, implicating AXL as an important target in cancer treatment. TT-00973-MS is a highly selective and potent AXL inhibitor which exhibited significant anti-tumor activities in both SK-OV-3 and H1299 derived CDX model with AXL over-expression. Here is first time to present the first-in-human study of TT-00973-MS. Methods: Dose escalation is performed using“3+3”design. Adverse events (AE) are evaluated per CTCAE v5.0 criteria. Tumor responses are evaluated per RECIST 1.1. Pts receive TT-00973-MS once daily continuously for 28-day cycles. The primary endpoint is to evaluate dose limiting toxicity (DLT) and identify the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). Results: As of the data cut-off date on December 24, 2024, 18 pts have received TT-00973-MS treatment in 2 mg (n = 1), 5 mg (n = 3), 10 mg (n = 3), 17 mg (n = 7), 25 mg (n = 4) at QD dose levels. Median age was 56.5 (37∼69), 8 (44.4%) were males, all had ECOG PS ≤1. 66.6% of pts had Stage III/IV disease. 50% had ≥3 prior lines of systemic therapies. 66.7% had prior immunotherapies. One DLT was observed in a subject at 17 mg QD dose level (Grade 3 peripheral motor nerve disorder). The MTD was not reached. Treatment-related AEs (TRAEs) were reported in all pts, grade 3 in 6 (33.3%), and no grade 4 or 5. The most common TRAE (≥30%) included increased blood lactate dehydrogenase (83.3%), increased aspartate aminotransferase (72.2%), increased alanine aminotransferase (66.7%), hypercholesterolaemia (55.6%), hypoalbuminaemia (38.9%), hypertriglyceridemia (33.3%) and proteinuria (33.3%). Fourteen pts were efficacy evaluable. Two confirmed partial remission (PR) were achieved in pts with renal pelvis cancer (n = 1) and ovarian cancer (n = 1). TT-00973-MS is slowly eliminated from body, with a half-life of about 55 h. After multiple dosing (QD), steady state was reached within 15 days, and the mean accumulation factor of AUC 0-24h was approximately 6. Preliminary PK analysis showed a linear increase on exposure. Plasma levels of soluble AXL (sAXL) increased to approximately 1.7 times (range: 0.9∼2.8) the baseline levels at C1D28. Conclusions: The preliminary findings from this phase I study demonstratedthat the AXL inhibitor TT-00973-MS monotherapy exhibits a well-tolerable safety profile, promising pharmacodynamic activity, with early signs of efficacy in pts with heavily pre-treated advanced solid tumors. Further studies are warranted to comprehensively evaluate the efficacy and safety of TT-00973-MS in large patient populations and specific tumor types. Clinical trial information: NCT05673538 .
- Research Article
1
- 10.3390/cancers17111816
- May 29, 2025
- Cancers
- Franchesca König + 13 more
Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome, brachial neuritis, and idiopathic brachial plexopathy, is a rare and potentially debilitating peripheral nerve disorder characterized by acute-onset shoulder pain followed by progressive motor deficits. It is often under-recognized, with an estimated incidence of 1 to 3 per 100,000 annually, though some studies suggest the actual prevalence may be significantly higher. The condition typically progresses through three phases, an acute painful phase, a phase of weakness, and a recovery phase, with sensory disturbances common in addition to motor weakness. The exact pathogenesis of NA remains unclear, though it is thought to involve a combination of genetic, environmental, and immunological factors. While neurologic complications following hematopoietic stem cell transplantation (HSCT), such as neuropathies and myopathies, have been documented, NA remains exceedingly rare in this context, with only a few reported cases. The pathophysiology in HSCT patients is hypothesized to involve immune dysregulation, graft-versus-host disease (GvHD), infection, and the effects of immunosuppressive therapy. Diagnosis is primarily clinical, supported by electrodiagnostic studies and MRI, though no laboratory markers exist. The management of NA is largely supportive and multimodal, focusing on pain control and rehabilitation. The objective of this study was to describe the characteristics, clinical course, and outcomes of patients admitted for HSCT who were subsequently diagnosed with NA. This retrospective case series from a single institution examined nine (N = 9) patients who developed acute shoulder pain following HSCT. We collected data on demographics, transplant details, clinical features, MRI findings, and electrodiagnostic studies, summarized using descriptive statistics. The diagnosis of neurologic amyotrophy was based on clinical presentation and corroborated by imaging and electrodiagnostic results. Long-term follow-up was assessed to evaluate symptom recovery. Between August 2020 and July 2022, nine patients (44% male, median age 60) were diagnosed with NA following autologous (n = 4) or allogeneic (n = 5) HSCT. The onset of severe shoulder pain occurred at a median of 9 days post-transplant (range 1-21 days), with the majority of patients experiencing unilateral pain, predominantly affecting the right shoulder (55%). Neurologic weakness developed on average 5.1 days after pain onset, and sensory deficits were observed in all but one patient. MRI findings revealed muscle edema, atrophy, and enhancement in six patients, while electromyography confirmed NA in five. Due to the small sample size, statistical analyses, including p-values, confidence intervals, and trend comparisons, were not performed, and thus no conclusions can be drawn regarding associations between variables such as early onset and worse outcomes. Shoulder pain resolved after a median of 23 days (range 8-40 days). Long-term follow-up (>1 year) showed that three patients achieved full or near-full recovery, four partially recovered, and two showed minimal improvement. Conclusions: NA should be highly suspected in patients with acute shoulder pain and neurologic symptoms post-HSCT. To improve diagnostic accuracy and clinical outcomes, we recommend enhanced clinician awareness, the implementation of targeted diagnostic protocols (such as MRI and electrodiagnostic studies), and the establishment of standardized long-term follow-up protocols.
- Research Article
1
- 10.4103/atn.atn-d-24-00036
- May 12, 2025
- Advanced Technology in Neuroscience
- Su Jiang + 2 more
Traditional open surgery for treating peripheral nerve disorders often leads to considerable trauma, scarring, and complications. However, with the ongoing advancements in microsurgical techniques, robotic-assisted minimally invasive surgery has emerged as a promising approach in the field of peripheral nerve disorder treatment. It combines innovative access techniques, such as the creation of artificial subcutaneous cavities, with telemanipulated instruments, enabling highly precise neurolysis, suturing, and grafting. Through incisions of less than 1 cm and enhanced three-dimensional visualization facilitated by CO2 insufflation, these procedures ensure superior visibility while minimizing tissue trauma. The clinical applications of this technology are diverse. For instance, neurolysis of the lateral cutaneous nerve of the thigh has shown promising results in the treatment of meralgia paresthetica, while experiments on the median nerve and ulnar nerve transposition highlight its potential for complex interventions. Techniques such as contralateral C7 root transfer or endoscopic repair of the brachial plexus further demonstrate that robotics can address the challenges of highly demanding pathologies, offering superior aesthetic and functional outcomes. Despite these advances, technological challenges remain, particularly in creating stable operative spaces and managing CO2 leakage. Additionally, the high cost of robotic systems limits their accessibility. To validate and generalize these techniques, large-scale clinical studies are needed. Furthermore, innovations such as augmented reality and artificial intelligence could further optimize these approaches. In conclusion, robot-assisted surgery of peripheral nerves provides significant benefits in terms of precision, safety, and aesthetic outcomes. With continued developments, it has the potential to redefine the standards of nerve surgery and transform the management of complex nerve lesions.
- Research Article
- 10.3390/neurosci6020039
- May 2, 2025
- NeuroSci
- Mrunalini Ramanathan + 7 more
Mesenchymal stem/stromal cells (MSCs) are non-hematopoietic, plastic-adherent, and self-renewing cells capable of in vitro trilineage differentiation into fat, bone, and cartilage tissue. Suggestively, MSCs have additional plasticity, as demonstrated by their ability to differentiate in vitro into myocytes, neuron-like cells, and hepatocytes. MSCs are ideal for therapeutic application owing to their numerous advantages; they exhibit limited growth and differentiation abilities, leading to heterogeneous cell populations with inconsistent functions. However, highly purified MSCs, namely, rapidly expanding clones (RECs) that are isolated by single-cell sorting, display uniform functionality. RECs have the potential to offer many benefits, such as transplantable cells for treating several disorders of bone, heart, peripheral nerves, brain, and other organs. This study aimed to assess the effects of RECs on the pheochromocytoma (PC12) cell line, a well-known neuronal cell model. PC12 cells were cultured under the following conditions: co-culture with RECs, treatment with REC-derived conditioned medium (CM), or co-culture with RECs using Transwell inserts for 7 days. The cells were stained with anti-βIII-tubulin antibody; the lengths of neurites were measured by image analysis. Regarding the co-culture with RECs, PC12's outgrowth was significantly increased. The RECs expressed nerve growth factor (NGF), a neurotrophic factor that could act on PC12 cells to trigger cellular differentiation. Our findings suggest that RECs via direct culture, intercellular communication in Transwell culture, and RECs CM promoted PC12 cell survival and outgrowth via NGF signaling.
- Research Article
1
- 10.1016/j.mric.2025.03.001
- May 1, 2025
- Magnetic resonance imaging clinics of North America
- Seungeun Lee + 2 more
Plexus and Peripheral Nerve MR Imaging: Advances and Applications: MR Neurography: Sequence Possibilities and Recent Advances.
- Research Article
- 10.1016/j.mric.2025.03.011
- May 1, 2025
- Magnetic resonance imaging clinics of North America
- Sonia Hafeez + 1 more
MR Imaging of Pediatric Nerve Disorders.
- Research Article
2
- 10.4103/aian.aian_751_24
- May 1, 2025
- Annals of Indian Academy of Neurology
- Devinderpal Singh Dhanota + 4 more
Magnetic resonance neurography (MRN) allows for the direct visualization of nerves, which can be instrumental in diagnosing, characterizing, and localizing peripheral nerve disorders. We planned to conduct a study on the patients of peripheral nerve injuries who were referred for MRN and to compare the findings of MRN to those of nerve conduction studies (NCS) on various focal nerve disorders. This prospective study was conducted over 1½ years, involving 58 subjects with clinically diagnosed focal peripheral nerve pathologies who were referred for MRN to the Department of Radiodiagnosis and Imaging. The range of focal peripheral nerve pathologies detected using MRN was correlated and compared to NCS and/or electromyography results, as well as to surgical and/or histopathological results, wherever available. The Chi-squared (χ²) test and Fisher's exact test were used to evaluate the association between MRN and NCS outcomes. The study identified a broad spectrum of peripheral nerve pathologies. Out of 58 subjects, abnormalities were found in 52 (89.6%) subjects, whereas six patients (10.3%) did not show any significant abnormalities. Fifty patients (86.3%) showed abnormalities on both MRN and NCS, while five patients (8.6%) did not show any abnormalities on either MRN or NCS. Two patients (3.4%) showed abnormalities on MRN but had normal NCS results, and in one case (1.7%), MRN was normal but NCS showed an abnormality. Out of the 58 MRN examinations, 25 were found to have brachial plexus involvement. MRN is a highly sensitive tool for evaluating peripheral nerve pathologies. Its correlation with NCS and intraoperative findings further supports its clinical utility. The 3 T MRN should be considered a key imaging modality in the diagnostic process for peripheral nerve pathologies. In addition, it serves as a valuable guide for planning therapeutic interventions and assessing prognosis in various patient subsets.
- Research Article
1
- 10.1186/s12974-025-03455-x
- Apr 29, 2025
- Journal of Neuroinflammation
- Huafang Jia + 8 more
BackgroundEpalrestat (EPS), an aldose reductase inhibitor, is used to alleviate peripheral nerve disorder of diabetic patients in clinical therapy. Even though EPS exerted effects in central nervous system diseases, the neuroprotection and underlying molecular mechanism in neurodegenerative diseases, especially Parkinson’s disease (PD), remains obscure. Our study aimed to investigate the potential of EPS suppressed PD progression both in vivo and in vitro.MethodsWe used 1-methyl-4-phenylpyridillium ion (MPP+)-treated PD cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD mice to investigate the protective function and molecular mechanism of EPS in PD. EPS was administered three times daily through oral route 3 days before model establishment for 5 consecutive days. Behavioral manifestation of mice was conducted using open field test, rotarod test and CatWalk gait analysis. Immunofluorescence was used to detect dopaminergic (DAergic) neurons survival in the substantia nigra. Subsequently, oxidative stress, mitochondrial function and KEAP1/Nrf2 signaling pathway in PD models were detected through molecular biology methods to assess the effect and downstream mechanisms of EPS on PD. Molecular docking, surface plasmon resonance and cellular thermal shift assay were used to verify the direct binding of EPS and KEAP1.ResultsWe found that EPS exhibited potent antiparkinsonian activity in PD models both in vivo and in vitro. PD models treated with EPS manifested alleviated oxidative stress and mitochondrial dysfunction. Furthermore, we found EPS activated the Nrf2 signaling pathway which contributed to DAergic neurons survival in PD models. Particularly, we firstly confirmed that EPS competitively binds to KEAP1 and enhanced its degradation, thereby activating the Nrf2 signaling pathway.ConclusionsCollectively, EPS attenuates oxidative stress and mitochondrial dysfunction by directly binding KEAP1 to activate the KEAP1/Nrf2 signaling pathway, further reducing DAergic neurons damage. These findings suggest that EPS has great potential to become a therapeutic for PD as a clinically effective and safe medicine.