Therapeutic Advances in Neurological Disorders最新文献

{"title":"Immunotherapy-mediated modulation of the gut microbiota in multiple sclerosis and associations with diet and clinical response-the effect of dimethyl fumarate therapy.","authors":"Elsebeth Staun-Ram, Anat Volkowich, Ariel Miller","doi":"10.1177/17562864241306565","DOIUrl":"https://doi.org/10.1177/17562864241306565","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence supports a role of the microbiota in health and disease, including in multiple sclerosis (MS). How MS drugs affect the microbiota and whether this is part of their mode of action is yet unknown.</p><p><strong>Objectives: </strong>To assess how dimethyl fumarate (DMF) affects the gut microbiota and whether the microbiota is associated with clinical response or adverse events (AEs) to DMF or diet.</p><p><strong>Design: </strong>An observational cohort study, in which the microbiota from 45 patients with relapsing-remitting MS pre-DMF initiation and following 6 months of DMF therapy, and from 47 matched healthy controls, were compared, and associations with clinical and dietary data assessed.</p><p><strong>Data sources and methods: </strong>Microbial DNA was sequenced and analyzed using MicrobiomeAnalyst. The clinical response was assessed after 1-year DMF therapy based upon evidence of disease activity (relapse, ΔEDSS increase >1, or MRI activity compared to pre-treatment). Dietary data were obtained by food questionnaires.</p><p><strong>Results: </strong>Alterations in relative abundance of several microbes were identified post 6-month DMF therapy compared to pre-treatment, including an increase in Firmicutes, <i>Lachnospiraceae</i>, and <i>Ruminococcaceae</i>, while reduction in Bacteroidetes and Proteobacteria. Patients who showed disease activity within 1 year from DMF initiation had pre-treatment higher abundance of Proteobacteria, <i>Flavonifractor</i>, and <i>Acidaminococcaceae</i>, while lower abundance of Firmicutes, <i>Ruminococcaceae</i>, <i>Butyricicoccus</i>, and <i>Massiliprevotella massiliensis</i>, compared to patients without disease activity. Patients who discontinued DMF therapy due to AEs had pre-treatment higher abundance of Proteobacteria, Bacteroidetes, <i>Eggerthella</i>, and <i>Lachnoclostridium</i> and lower abundance of <i>Ruminococcaceae</i>, <i>Megamonas</i>, and <i>Holdemanella</i>, among others. Differentially abundant microbes correlated with intake of several nutrients.</p><p><strong>Conclusion: </strong>DMF immunotherapy is associated with modifications of the microbiota. The microbiota may affect the severity of AEs and the clinical response to DMF, and is potentially modulated by diet. Microbiota-based, personalized treatment approach, integrating pharmacotherapy with dietary components, carries potential to improved clinical outcome.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241306565"},"PeriodicalIF":4.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatigue, sleep quality, depression symptoms, and antiseizure medication resistance in patients with newly diagnosed epilepsy.","authors":"Rui Zhong, Teng Zhao, Nan Li, Jing Li, Guangjian Li, Xinyue Zhang, Weihong Lin","doi":"10.1177/17562864251325338","DOIUrl":"10.1177/17562864251325338","url":null,"abstract":"<p><strong>Background: </strong>Complaints of fatigue and poor sleep quality are common in patients with epilepsy. Fatigue may precipitate seizures, and patients with poor sleep quality have higher frequency of seizures and are more likely to have symptoms of depression.</p><p><strong>Objectives: </strong>This study aims to determine the association of baseline fatigue and sleep quality with antiseizure medication (ASM) resistance in patients with newly diagnosed epilepsy (PWNDE). We also evaluate whether the association is mediated by depression symptoms.</p><p><strong>Methods: </strong>We performed a prospective cohort study of PWNDE at comprehensive epilepsy center in Northeast China between June 2020 and May 2024. Fatigue, sleep quality, and depression symptoms were assessed at baseline. All patients were followed for 24 months for ASM-resistant epilepsy. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of ASM resistance. Models fitted with restricted cubic spline were performed to test for linear and nonlinear shapes of each association. Mediation analysis was used to estimate the mediating effects of depression severity on association between fatigue, sleep quality, and ASM resistance.</p><p><strong>Results: </strong>A total of 189 patients (59 ASM-resistant cases and 130 ASM-responsive controls) were included in the final analysis. Baseline fatigue (HR, 1.98; 95% confidence interval (CI), 1.094-3.583, <i>p</i> = 0.024) and poor sleep quality (HR, 2.193; 95% CI, 1.29-3.729, <i>p</i> = 0.004) were associated with an increased hazard of ASM resistance in PWNDE after full adjustments. There exists a nonlinear association between Fatigue Severity Scale score and the hazard of ASM resistance (<i>P</i> for nonlinear = 0.012). Depression severity partly mediated the effect of fatigue and sleep quality on ASM resistance, with mediated proportions of 18.5% for the fatigue and 23.7% for the sleep quality.</p><p><strong>Conclusion: </strong>Baseline fatigue and poor sleep quality were associated with an increased risk of ASM resistance. The association between fatigue, sleep quality, and ASM resistance were partly mediated by depression severity. These findings emphasize that patients with ASM-resistant epilepsy are more likely to have fatigue, depression, and poor sleep quality at baseline and this may be unrelated to ASM intake.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251325338"},"PeriodicalIF":4.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CACNA1S</i>-associated triadopathy presenting with myalgia, muscle weakness, and asymptomatic hyperCKemia.","authors":"Si Luo, Min Zhu, Dandan Tan, Yusen Qiu, Meihong Zhou, Daojun Hong","doi":"10.1177/17562864251317961","DOIUrl":"10.1177/17562864251317961","url":null,"abstract":"<p><p><i>CACNA1S</i> variants can alter the structure and function of the calcium channel, resulting in abnormal calcium influx and homeostasis. It is well established that pathogenic variants in <i>CACNA1S</i> can lead to hypokalemic periodic paralysis, malignant hyperthermia, and congenital myopathy. Nevertheless, the clinical presentations and disease progression of exertional myalgia and weakness associated with <i>CACNA1S</i> variants remain elusive. In this study, four affected individuals from an autosomal-dominant family were described, exhibiting symptoms of severe exertional myalgia, followed by flaccid weakness or rhabdomyolysis, along with asymptomatic hyperCKemia during the interictal period. Long exercise test showed a late decrease in compound muscle action potential amplitude. Muscle MRI revealed edema-like changes in the early stage, and fatty degeneration and substitution in prolonged disease courses, while closely aligned with the features of chronic myopathy. Ultrastructural examination revealed dilation of the sarcoplasmic reticulum and myofibrillar structural disarrangement. Genetic screening identified a c.3724A>G (p.Arg1242Gly) mutation in the <i>CACNA1S</i> gene. A literature review revealed that 15 patients exhibited the exertional myalgia and weakness phenotype associated with CACNA1S mutations, presenting similar clinical, electrophysiological, radiological, and pathological features. As the disease progressed, these patients developed severe muscle weakness, ultimately leading to wheelchair dependency. This exertional myalgia-weakness phenotype represented a unique <i>CACNA1S</i>-related phenotype that broadened the spectrum of <i>CACNA1S</i>-associated myopathy, bridging between periodic paralysis and congenital myopathies. The similarities between <i>CACNA1S</i>-associated myalgia-weakness and RyR1-associated myalgia-weakness underscored a shared pathogenesis of excitatory-contractile coupling at the triad of skeletal muscle.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251317961"},"PeriodicalIF":4.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential administration of efgartigimod shortened the course of Guillain-Barré syndrome: a case series.","authors":"Sihui Chen, Ruwei Ou, Qianqian Wei, Bi Zhao, Xueping Chen","doi":"10.1177/17562864251314746","DOIUrl":"10.1177/17562864251314746","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) is a serious neurological condition with limited treatment options. A recent report demonstrated successful treatment with efgartigimod alone in two patients with GBS, although it did not significantly shorten the disease duration. This case series investigates the effects of sequential efgartigimod administration in patients with different GBS phenotypes and varying levels of disease severity. All three patients tested positive for immunoglobulin G (IgG) antibodies against serum gangliosides. In Case 1, the patient was treated with 0.4 g/kg of intravenous immunoglobulin (IVIg) for 5 days, showing minimal recovery. After receiving 3 weekly doses of efgartigimod (10 mg/kg), the patient achieved independent ambulation 19 days post-onset, with a reduction in serum ganglioside antibody titers and total IgG levels. Case 2 involved a middle-aged man with Miller Fisher syndrome (MFS)-GBS overlap, who experienced worsened autonomic dysfunction following IVIg treatment. After three doses of efgartigimod, the patient showed symptom improvement within 1 month, alongside a reduction in IgG antibody levels. In Case 3, a 27-year-old male with MFS-GBS overlap, initially unresponsive to IVIg, showed significant improvement in ophthalmoplegia following two doses of efgartigimod, with his serum ganglioside antibodies eventually becoming undetectable. Our findings suggest that sequential efgartigimod treatment may effectively reduce serum anti-ganglioside antibody titers and potentially shorten the disease course in severe GBS and MFS-GBS overlap syndrome. Additionally, it may offer clinical benefits for patients with GBS who have a poor or no response to IVIg, particularly in treating ophthalmoplegia.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251314746"},"PeriodicalIF":4.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiating idiopathic Parkinson's disease from multiple system atrophy-P using brain MRI-based radiomics: a multicenter study.","authors":"Yin-Hui Huang, Mei-Li Yang, Yuan-Zhe Li, Ya-Fang Chen, Chi Cai, Jing Huang, Yi Wang, Tie-Qiang Li, Qin-Yong Ye","doi":"10.1177/17562864251318865","DOIUrl":"10.1177/17562864251318865","url":null,"abstract":"<p><strong>Background: </strong>Differentiating idiopathic Parkinson's disease (IPD) from multiple system atrophy-parkinsonian type (MSA-P) is essential for optimizing patient care and prognosis, given the differences in disease progression and treatment response.</p><p><strong>Objectives: </strong>This study aimed to develop and evaluate a radiomics-based model using magnetic resonance imaging (MRI)-derived features to distinguish IPD from MSA-P.</p><p><strong>Design: </strong>A multicenter retrospective study.</p><p><strong>Methods: </strong>A multicenter retrospective study was conducted with 287 patients (186 IPD and 101 MSA-P) who underwent brain MRI. Radiomic features were extracted from T1-weighted imaging and T2-weighted imaging sequences, and various machine learning classifiers were applied, including logistic regression, support vector machine (SVM), ExtraTrees, extreme gradient boosting, and Light Gradient Boosting Machine. Model performance was assessed using area under the curve (AUC), accuracy, sensitivity, and specificity. A nomogram combining clinical and radiomic features was also evaluated.</p><p><strong>Results: </strong>The SVM model, selected as the base for the Rad-signature, achieved the best diagnostic performance, with AUCs of 0.885 and 0.900 in the training and testing cohorts, respectively. The Rad-signature significantly outperformed clinical-only models in distinguishing IPD from MSA-P. The nomogram incorporating radiomic and clinical features yielded the highest diagnostic accuracy (AUC = 0.973 and 0.963 for training and testing cohorts, respectively) and balanced sensitivity and specificity. Decision curve analysis confirmed the nomogram's clinical utility.</p><p><strong>Conclusion: </strong>Radiomics-based MRI analysis offers a powerful tool for distinguishing IPD from MSA-P, enhancing diagnostic accuracy, and aiding personalized treatment planning. Integrating radiomic and clinical data may improve diagnostic workflows in clinical practice.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251318865"},"PeriodicalIF":4.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of treatment efficacy and cost-effectiveness of rituximab and oral agents among patients with neuromyelitis optica spectrum disorders: a population-based cohort study.","authors":"Hye Lim Lee, Minwoong Kang, Jin Myoung Seok, Byung-Jo Kim, Byoung Joon Kim","doi":"10.1177/17562864251314020","DOIUrl":"10.1177/17562864251314020","url":null,"abstract":"<p><strong>Background: </strong>Rituximab (RTX) is a well-known effective treatment for neuromyelitis optica spectrum disorder (NMOSD).</p><p><strong>Aims: </strong>To investigate the effectiveness of RTX treatment in patients with NMOSD and compared medical expenses between RTX and other oral agents.</p><p><strong>Methods: </strong>Using data from the National Health Insurance System database (2010-2021), we compared the time to the first relapse and medical expenses after each medication between groups with RTX and oral agents. Also, we analyzed the association between the level of disability and the type of drugs.</p><p><strong>Results: </strong>A total of 899 patients were included, and they were divided into two groups according to the type of treatment. The group treated with RTX had a lower risk of relapse than those treated with other oral agents (hazard ratio, 0.479, <i>p</i> < 0.001). Regarding medical expenses, the increase in total medical costs was associated with the use of RTX and the number of relapses. The increase in medical costs was higher in cases with increased disability owing to NMOSD after adjustment for the number of relapses.</p><p><strong>Conclusion: </strong>In comparison to other oral agents, RTX showed a favorable treatment effect. It is also relatively cost-effective, considering the change in disability in a large-scale real-world nationwide study.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251314020"},"PeriodicalIF":4.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolution of bilateral temporal lobe epilepsy via minimally invasive stereoelectroencephalogram-guided asymmetric radiofrequency thermocoagulation: a case report.","authors":"Zhao Liu, Guoming Luan, Mengyang Wang, Jing Wang, Pengfei Teng, Yuguang Guan, Xiongfei Wang, Tianfu Li, Tianyi Cui, Jian Zhou","doi":"10.1177/17562864251321255","DOIUrl":"10.1177/17562864251321255","url":null,"abstract":"<p><p>Bilateral temporal lobe epilepsy (TLE) is a complex form of epilepsy, characterized by seizures originating from both temporal lobes. Its intricate nature presents significant challenges for both medical and surgical treatment, often necessitating a multidisciplinary approach. While resective surgery is generally unsuitable for bilateral TLE, neuromodulation offers more of a remission-focused approach, which better preserves neuropsychological function. In this study, we presented the case of a 45-year-old female with a 16-years history of recurrent seizures, diagnosed as drug-resistant bilateral TLE. After a comprehensive multidisciplinary epilepsy evaluation-encompassing detailed patient history, neurological examination, scalp audiovisual electroencephalogram monitoring, high-resolution brain magnetic resonance imaging, neuropsychological testing, and cerebrospinal fluid analysis-stereoelectroencephalogram (SEEG) confirmed the diagnosis. The patient subsequently underwent asymmetric radiofrequency thermocoagulation guided by SEEG results, targeting bilateral temporal lobes. Despite experiencing transient psychiatric symptoms postprocedure, she achieved seizure freedom and showed improved neuropsychological function over a 3-year follow-up period. This case demonstrates that, with thorough evaluation, seizure freedom is attainable in bilateral TLE patients, even when bilateral injury is present, without significant impairment to neuropsychological function.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251321255"},"PeriodicalIF":4.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained-release oral dalfampridine appears to have no impact on upper extremity function in people with multiple sclerosis: a randomized controlled trial.","authors":"Shay Menascu, Lior Frid, Alon Kalron","doi":"10.1177/17562864251321696","DOIUrl":"10.1177/17562864251321696","url":null,"abstract":"<p><strong>Background: </strong>Upper limb dysfunction is common in people with multiple sclerosis (pwMS), significantly affecting daily activities and quality of life. While dalfampridine has shown efficacy in improving gait in pwMS, its impact on upper extremity function remains unclear.</p><p><strong>Objectives: </strong>To evaluate the effect of sustained-release oral dalfampridine on upper extremity function in pwMS.</p><p><strong>Design: </strong>A randomized, placebo-controlled trial.</p><p><strong>Methods: </strong>In all, 30 pwMS were randomized to receive either dalfampridine (10 mg twice daily) or a placebo for 2 weeks. Upper extremity function was assessed at baseline, after 1 week, after 2 weeks of treatment, and 2 weeks post-treatment using clinical tests (9-Hole Peg Test, Box, and Block Test, peak isometric grip force, 2-point discrimination) and self-reported questionnaires (disabilities of the arm, shoulder and hand, ability measure of the hand, Manual Ability Measurement 36). Data were analyzed using repeated-measures analysis of variance to evaluate group × time interactions.</p><p><strong>Results: </strong>No significant group × time interactions were observed across clinical or self-reported outcomes. Both groups exhibited similar trends over time, with no measurable improvements in upper extremity dexterity, strength, or perceived function attributable to dalfampridine.</p><p><strong>Conclusion: </strong>Sustained-release dalfampridine does not appear to improve upper extremity function in pwMS, highlighting its limitations beyond gait-related benefits. These findings underscore the need for further research to explore alternative treatments targeting upper limb dysfunction in this population.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT02259361.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251321696"},"PeriodicalIF":4.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between the gut microbiota and brain network topology in poststroke aphasia patients: perspectives from neuroimaging findings.","authors":"Yun Cao, Jiaqin Huang, Danli Zhang, Jianguang Ji, Xiaojing Lei, Zhongjian Tan, Jingling Chang","doi":"10.1177/17562864251319870","DOIUrl":"10.1177/17562864251319870","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence indicates that gut inflammatory and immune response play a key role in the pathophysiology of stroke and may become a promising therapeutic target. However, the specific role of the microbiota-gut-brain axis in poststroke aphasia (PSA) patients remains unclear.</p><p><strong>Objectives: </strong>The aim of this study was to investigate the relationships among the gut microbiota, neuroendocrine-immune network, brain network properties, and language function in patients with PSA.</p><p><strong>Design: </strong>This is a cross-sectional, observational, monocentric study.</p><p><strong>Methods: </strong>This study enrolled 15 PSA patients, 10 non-PSA patients, and 15 healthy controls (HCs). All subjects underwent stool microbiota analysis, blood inflammatory cytokines assessment, and brain-gut peptide examination. PSA patients and HCs underwent additional resting-state functional MRI (rs-fMRI) brain scans. The rs-fMRI data were utilized to create whole-brain connectivity maps, and graph theory was employed to characterize the network topological properties. Analysis of variance and the Kruskal-Wallis test were used for comparisons among the three groups. Correlation analyses were subsequently conducted to explore relationships among factors showing significant group differences.</p><p><strong>Results: </strong>Compared with non-PSA patients and HCs, PSA patients displayed alterations in the gut microbiota composition, increased systemic inflammation, changes in brain-gut peptides, and had worse language performance. Graph theoretical analysis revealed that PSA patients exhibited small-world topology. Furthermore, nodal measures in brain network analysis showed activation of homologous speech areas in the right hemisphere, while the nodal properties of brain regions near the lesion in the left hemisphere decreased in patients with PSA compared with HCs.</p><p><strong>Conclusion: </strong>The present study revealed, for the first time, that an imbalance in gut microbiota was accompanied by the neuroendocrine-immune network disorder and abnormal changes in the brain network in PSA patients.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251319870"},"PeriodicalIF":4.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF IL-6, GDF-15, GFAP and NfL levels in early Alzheimer disease: a pilot study.","authors":"Domenico Plantone, Matteo Pardini, Carlo Manco, Delia Righi, Paolo Alessandro Alì, Dario Arnaldi, Virginia Pelagotti, Federico Massa, Miriana d'Alessandro, Elena Bargagli, Nicola De Stefano","doi":"10.1177/17562864251314773","DOIUrl":"10.1177/17562864251314773","url":null,"abstract":"<p><strong>Background: </strong>Despite their potential usefulness as biomarkers, no study has investigated the interactions between cerebrospinal fluid (CSF) changes of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), growth differentiation factor 15 (GDF-15), transactive response DNA binding protein (TDP-43) and interleukin-6 (IL-6) and the core AD CSF biomarkers in the same cohort of AD patients.</p><p><strong>Objectives: </strong>The aim of this pilot study is to evaluate the CSF levels of these analytes in patients with AD and assess their clinical relevance in this neurological condition.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Methods: </strong>We assessed the levels of NfL, GFAP, GDF-15, TDP-43 and IL-6 in the CSF samples of 52 early AD patients and evaluated their partial reciprocal correlations and those with Abeta42, p-Tau, t-Tau and Mini-Mental State Examination (MMSE), always adding age, sex and educational level as covariates.</p><p><strong>Results: </strong>MMSE score showed a positive correlation with the Aβ 1-42 concentrations (<i>r</i> = 0.485; <i>p</i> < 0.001), and a negative correlation with GDF-15 concentrations (<i>r</i> = -0.418; <i>p</i> = 0.002). IL-6 concentrations showed a positive correlation with NfL concentrations (<i>r</i> = 0.312; <i>p</i> = 0.026) and a negative correlation with TDP-43 concentrations (<i>r</i> = -0.322; <i>p</i> = 0.021). TDP-43 concentrations showed a positive correlation with GFAP (<i>r</i> = 0.33, <i>p</i> = 0.018). The mediation analysis suggests that the association between GDF-15 and MMSE is primarily mediated by Aβ 1-42. CSF GDF-15 concentrations were higher in AD patients with low Aβ 1-42 concentrations than those with high Aβ 1-42 concentrations (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Our findings highlight that CSF IL-6 levels correlate positively with markers of neuronal damage. CSF TDP-43 levels significantly correlated with GFAP, suggesting a potential link with reactive gliosis and astrocyte activation. In addition, while CSF GDF-15 levels negatively correlate with MMSE scores, mediation analysis revealed that this association is primarily indirect and mediated through Aβ 1-42 levels.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251314773"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}