Annals of Clinical and Translational Neurology最新文献

{"title":"The Relationship Between Inflammation and Central Nervous System in Multiple Sclerosis.","authors":"Gamze Ansen, Ali Behram Salar, Abdulkadir Ermis, Erkingul Birday, Lutfu Hanoglu, Bayram Ufuk Sakul","doi":"10.1002/acn3.70231","DOIUrl":"https://doi.org/10.1002/acn3.70231","url":null,"abstract":"<p><strong>Aim: </strong>Multiple sclerosis is an autoimmune demyelination disease that is seen especially in the young population and has a progressive course, causing motor, sensory, and cognitive deficits. In the literature, the pathogenesis of MS disease and the interconnection between the immune and central nervous system in the disease have not been fully revealed. Recent studies indicate that gray matter damage, as well as white matter lesions, are frequently seen in MS patients. Based on this background, the present study aimed to explore whether relapsing-remitting MS patients in the attack phase demonstrate different patterns of functional connectivity compared to those in a stable phase.</p><p><strong>Material and method: </strong>For this purpose, resting-state fMRI findings of the attack (n = 5) and stable (n = 14) groups were examined.</p><p><strong>Results: </strong>Compared to stable patients, the attack group appeared to show increased functional connectivity in several gray matter structures, including the left fusiform, posterior cingulate, orbitofrontal cortex, left supramarginal gyrus, thalamus, and precuneus.</p><p><strong>Conclusion: </strong>The findings indicate that patients in the inflammatory phase may exhibit increased activation in distinct gray matter regions relative to those not in the attack phase. This pattern might reflect the development of compensatory functional connections aimed at limiting potential clinical damage during relapse. Moreover, considering the diverse roles of these regions, their involvement could hypothetically be linked to immune-related processes, a possibility that warrants further investigation in larger cohorts.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Tilburg Frailty on Poststroke Fatigue in First-Ever Stroke Patients: A Cross-Sectional Study With Unified Measurement Tools and Improved Statistics.","authors":"Chuan-Bang Chen, Xiao-Xue Wang, Shao-Rui Bao, Sui-Li Lin, Mei-Chun Shu, Xi-Xi Ye, Wen-Jie Cong","doi":"10.1002/acn3.70202","DOIUrl":"https://doi.org/10.1002/acn3.70202","url":null,"abstract":"<p><strong>Background: </strong>Poststroke fatigue (PSF) and frailty share substantial overlap in their manifestations, yet previous research has yielded conflicting results due to the use of heterogeneous frailty assessment tools.</p><p><strong>Objective: </strong>To evaluate the independent impact of frailty on PSF using a unified measurement system (Tilburg Frailty Indicator, TFI) while controlling for modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), anxiety, depression, and other confounding factors.</p><p><strong>Methods: </strong>A single-center cross-sectional study was conducted with 320 first-ever stroke patients. Frailty was assessed using the TFI, fatigue with the Fatigue Severity Scale (FSS), and psychological symptoms with the Hospital Anxiety and Depression Scale (HADS). Both linear regression and logistic regression models were employed, with quantile regression for robustness testing.</p><p><strong>Results: </strong>TFI total score demonstrated a strong positive correlation with FSS scores (ρ = 0.85, p < 0.001). Here, frailty (independent variable) was captured by TFI and poststroke fatigue (dependent variable) by FSS. In multivariable regression analysis, TFI (β = 0.42, 95% CI: 0.35-0.49), HADS-A (β = 0.28, 95% CI: 0.21-0.35), and NIHSS (β = 0.18, 95% CI: 0.11-0.25) emerged as significant predictors of PSF (all p < 0.001). The combined model explained 74.2% of variance in fatigue scores.</p><p><strong>Conclusion: </strong>The use of the unified frailty assessment tool (TFI) resolves previous conflicting findings and confirms that frailty is a strong independent predictor of PSF. Routine frailty assessment using the TFI should be incorporated into poststroke care to identify patients at high risk for fatigue and guide targeted interventions.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Stress-Induced Hyperglycemia on In-Hospital Medical Complications in Patients With Acute Stroke: From a Large-Scale Nationwide Longitudinal Registry.","authors":"Xintong Song, Yi Ju, Hongqiu Gu, Zhikai Zhu, Zixiao Li, Qian Zhang, Xingquan Zhao","doi":"10.1002/acn3.70228","DOIUrl":"https://doi.org/10.1002/acn3.70228","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to explore the relationship between stress-induced hyperglycemia (SIH) and in-hospital medical complications in patients with acute stroke.</p><p><strong>Methods: </strong>We enrolled 865,765 patients with acute stroke from the Chinese Stroke Center Alliance cohort. The stress hyperglycemia ratio (SHR) was defined as the ratio of fasting blood glucose to glycosylated hemoglobin. The primary outcomes were in-hospital medical complications, including urinary tract infection (UTI), pneumonia, deep venous thrombosis (DVT), pulmonary embolism (PE), gastrointestinal bleeding (GIB), and pressure sores. Logistic regression analyses were performed to assess the association between the SHR and in-hospital medical complications.</p><p><strong>Results: </strong>In total, 104,873 (12.11%) patients with acute stroke experienced at least one in-hospital medical complication. The most frequently observed complications were pneumonia (9.84%), UTI (1.29%), and GIB (1.06%). Both univariate and multivariate logistic regression analyses showed that a higher SHR was associated with a higher prevalence of pneumonia, UTI, GIB, and pressure sores (P for trend < 0.01). After adjusting for potential confounders, a higher SHR was associated with a reduced risk of PE (P for trend < 0.05), whereas no significant association was found between SHR and DVT. In the subgroup analysis, a significant association between elevated SHR and the occurrence of in-hospital complications was further confirmed.</p><p><strong>Conclusions: </strong>SIH is significantly associated with in-hospital medical complications, particularly pneumonia, UTI, GIB, and pressure sores, in patients with acute stroke.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Overview of the Clinical, Electrophysiological, and Neuroimaging Features of BPAN: Insights From a New Case Series.","authors":"Seda Susgun, Ozgu Kizek, Sibel Aylin Ugur Iseri, Ibrahim Kamaci, Ayse Deniz Elmali, Pinar Iscen, Berfin Gulkaya Guzel, Gul Yalcin Cakmakli, Bulent Elibol, Berril Donmez, Raif Cakmur, Pinar Topaloglu, Nerses Bebek, Murat Emre, Zuhal Yapici","doi":"10.1002/acn3.70220","DOIUrl":"https://doi.org/10.1002/acn3.70220","url":null,"abstract":"<p><strong>Background: </strong>Neurodegeneration with brain iron accumulation (NBIA) comprises a genetically and clinically heterogeneous group of rare neurological disorders characterized particularly by iron accumulation in the basal ganglia. To date, 15 genes have been associated with NBIA. Among them, WDR45, linked to beta-propeller protein-associated neurodegeneration (BPAN), represents the only X-linked dominant subtype of NBIA. Herein, clinical, electrophysiological, and neuroimaging evaluations were used to broaden the understanding of BPAN in a newly reported case series.</p><p><strong>Methods: </strong>This study included 10 individuals with BPAN, categorized into three age groups. WDR45 variant data retrieved from next-generation sequencing or Sanger sequencing were reviewed and reassessed. Comprehensive clinical evaluations including magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and video electroencephalographic monitoring were conducted.</p><p><strong>Results: </strong>The clinical manifestations were highly heterogeneous, with cognitive impairment being a consistent finding among the patients, with variable severity. The associated WDR45 variants are likely to exert loss-of-function effects. Electroencephalogram (EEG) abnormalities included age-dependent background slowing and epileptiform discharges. MRI indicated a characteristic pattern, while two patients lacked these typical findings. FDG-PET imaging demonstrated hypometabolism extending beyond cerebral structures, with predominant cerebellar and pontine involvement in pediatric patients and frontoparietal hypometabolism in adults.</p><p><strong>Conclusions: </strong>This study contributes further to our understanding of the heterogeneous clinical spectrum of BPAN. Genotype-phenotype correlation in BPAN remains unclear due to the absence of sufficiently large cohorts in the literature, including the present study. Nevertheless, even within this small sample, the phenotypic heterogeneity observed among individuals harboring the same genotype highlights the biological complexity of the disease. Neuroimaging findings may reflect progressive and widespread neurological involvement in an age-dependent pattern, whereas EEG data suggest that epilepsy severity tends to decrease after adolescence.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of APOE ε4 Genotype Load on Cognitive Function and Lipid Metabolism in Patients With Cerebral Small Vessel Disease.","authors":"Tingru Jin, Haocheng Yang, Feng Liu, Sihao Lin, Junru Hu, Jian Wang, Yulan Gou","doi":"10.1002/acn3.70224","DOIUrl":"https://doi.org/10.1002/acn3.70224","url":null,"abstract":"<p><strong>Background: </strong>Apolipoprotein ε4 (APOE ε4) is a potent genetic risk factor for Alzheimer's disease (AD). However, its role in cerebral small vessel disease (CSVD) remains unclear. Given the clinical and pathological similarities between CSVD and AD, this study aimed to investigate the associations of APOE ε4 gene dosage with cognitive function and dyslipidemia in CSVD patients, and to explore whether lipid disturbances mediate the effect of APOE ε4 on white matter hyperintensity (WMH) burden and cognitive impairment.</p><p><strong>Methods: </strong>The study was a retrospective study. A total of 717 inpatients with CSVD admitted to the Department of Neurology, Wuhan No.1 Hospital, from January 2023 to January 2025 were enrolled. Associations among APOE ε4 gene dosage, cognitive function, lipid metabolism, and WMH were analyzed.</p><p><strong>Results: </strong>The number of APOE ε4 alleles showed a significant negative correlation with MMSE and MoCA scores (p < 0.001), and a dose-dependent positive correlation with the risk of cognitive impairment and WMH severity, independent of traditional vascular risk factors. Lipid analysis indicated that APOE ε4 was an independent risk factor for elevated low-density lipoprotein cholesterol (LDL-C), but had no significant associations with high-density lipoprotein cholesterol (HDL-C) or triglycerides (TG). Mediation analysis suggested that LDL-C may mediate the indirect detrimental effect of APOE ε4 on cognitive function.</p><p><strong>Conclusion: </strong>APOE ε4 gene dosage is an independent risk factor for cognitive decline and WMH in CSVD patients, independent of traditional vascular risk factors. APOE ε4 may indirectly impair cognitive function by elevating LDL-C levels to exacerbate atherosclerosis and cerebrovascular injury.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The MMP-9/TIMP-1 Ratio and Concentrations of Osteopontin Are Elevated in Cerebrospinal Fluid of People With Multiple Sclerosis and Decrease After Autologous Hematopoietic Stem Cell Transplantation.","authors":"Ivan Pavlovic, Ida Erngren, Kim Kultima, Anders Larsson, Malin Müller, Anna Wiberg, Joachim Burman","doi":"10.1002/acn3.70229","DOIUrl":"https://doi.org/10.1002/acn3.70229","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the utility of cerebrospinal fluid (CSF) biomarkers-matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), the MMP-9/TIMP-1 ratio, and osteopontin (OPN)-as indicators of blood-brain barrier (BBB) integrity and disease activity in people with relapsing-remitting multiple sclerosis (pwMS), and to assess their changes following autologous hematopoietic stem cell transplantation (aHSCT).</p><p><strong>Methods: </strong>CSF samples from pwMS treated with aHSCT (n = 43) and healthy controls (n = 32) were analyzed for MMP-9, TIMP-1, and OPN concentrations using ELISA and electrochemiluminescence assays. Lumbar punctures were performed at baseline and at 1, 2, and 3-5 years post-aHSCT. Biomarker findings were compared with standard CSF parameters, prior treatments, and MRI data.</p><p><strong>Results: </strong>MMP-9/TIMP-1 ratios and OPN levels were significantly elevated in pwMS compared to controls, particularly in those with gadolinium-enhancing lesions or on first-line therapies. Both biomarkers declined significantly after aHSCT and remained low during follow-up. The MMP-9/TIMP-1 ratio showed superior discriminatory capacity and correlated with inflammatory CSF markers.</p><p><strong>Interpretation: </strong>CSF MMP-9/TIMP-1 ratio and OPN are elevated in MS and decrease following aHSCT, reflecting reduced inflammation and restored BBB integrity. These biomarkers may support disease monitoring and therapeutic evaluation.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyotrophic Lateral Sclerosis Prevalence Projection in 2040: A Less Rare Disease.","authors":"Rosario Vasta, Stefano Callegaro, Antonio Canosa, Umberto Manera, Maurizio Grassano, Francesca Palumbo, Sara Cabras, Enrico Matteoni, Francesca Di Pede, Filippo De Mattei, Salvatore Tafaro, Neil M Thakur, Ryan Grosenick, Fabiola De Marchi, Letizia Mazzini, Cristina Moglia, Andrea Calvo, Kuldip D Dave, Adriano Chiò","doi":"10.1002/acn3.70226","DOIUrl":"https://doi.org/10.1002/acn3.70226","url":null,"abstract":"<p><strong>Objective: </strong>To project ALS prevalence across multiple countries through 2040, accounting for both population aging and increased survival.</p><p><strong>Methods: </strong>Data from the Piemonte and Valle d'Aosta ALS register (PARALS) was used to estimate the trends in incidence and prevalence from 2005 to 2019. Survival trends over this period were also assessed. The observed annual increase was then projected into future years up to 2040. Concurrently, the incidence for each future year was calculated using population projections. Finally, the prevalence rate for each year was estimated as the product of the projected incidence and the projected survival. We also estimated survival for fifteen countries by dividing prevalence by incidence, based on available data, and applied the same increase observed in PARALS to project prevalence in these countries up to 2040.</p><p><strong>Results: </strong>Using data from 3294 patients, we determined that ALS survival increased by 0.06 years annually from 2005 to 2019 in Piemonte and Valle d'Aosta. Considering changes in incidence due to population aging, the prevalence is projected to reach 15.72 per 100,000 population by 2040 in this area, while rising by a median of 24.9% across multiple countries worldwide. If a new drug could provide a 6-month increase in survival starting in 2025, disease prevalence would rise by 37.8% by 2040. We provided a web interface so users can model different data and assumptions.</p><p><strong>Interpretation: </strong>ALS prevalence is projected to increase significantly over the next decades. This underscores the need for careful planning and allocation of public health resources.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Proteomic Signatures for Alzheimer's Disease: Comparable Accuracy to ATN Biomarkers and Cross-Platform Validation.","authors":"Manyue Hu, Oliver Robinson, Christina M Lill, Anna Matton, Raquel Puerta, Pilar Sanz, Merce Boada, Agustín Ruiz, Lefkos Middleton","doi":"10.1002/acn3.70227","DOIUrl":"https://doi.org/10.1002/acn3.70227","url":null,"abstract":"<p><strong>Background: </strong>There is growing recognition of the potential of plasma proteomics for Alzheimer's Disease (AD) risk assessment and disease characterization. However, differences between proteomics platforms introduce uncertainties regarding cross-platform applicability.</p><p><strong>Objective: </strong>We aimed to identify a detailed plasma biosignature for distinguishing AD from cognitively normal (CN) and another signature for classifying mild cognitive impairment (MCI) decliners and non-decliners. We also explored the cross-platform applicability of these models between two proteomic platforms.</p><p><strong>Methods: </strong>Elastic net was performed on 190 plasma analytes measured using the Luminex xMAP platform in 566 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to model MCI stable/decliner and AD/CN classification. MCI decliner was defined as progression to AD during follow-up (mean 4.2 ± 3.2 years). External cross-platform validation was conducted with 1303 participants from the Spanish Ace study, using the SOMAscan 7k platform.</p><p><strong>Results: </strong>An 11-analyte signature for distinguishing AD from CN achieved a 93.5% accuracy on ADNI and 95.2% on Ace. The ApoE and BNP proteins were the two most important contributors to the classifier. The MCI classification signature performed less well, with 65.9% accuracy on ADNI and 51.0% accuracy upon validation testing in Ace.</p><p><strong>Discussion: </strong>Compared with prior proteomic-based studies on the same dataset, our findings attained higher specificity and sensitivity for AD classification while utilizing a smaller panel of analytes. We also confirmed the reliability and consistency of this signature within a different population from a different platform. The plasma proteomic platforms explored were, however, not sufficient to determine MCI decliners versus non-decliners.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased Serum 5-HT: Clinical Correlates and Regulatory Role in NMJ of MG.","authors":"Xinru Shen, Jing Zhang, Xinyue Zhou, Xiaoxiao Yu, Haodong Shang, Shufan Chen, Lulu Zhen, Jinru Wu, Guanlian Hu, Xiaoyan Zhu, Zhan Sun, Yiren Wang, Jiahui Wang, Jie Lv, Xue Zhao, Yingna Zhang, Wei Guo, Ying Peng, Feng Gao","doi":"10.1002/acn3.70222","DOIUrl":"https://doi.org/10.1002/acn3.70222","url":null,"abstract":"<p><strong>Objective: </strong>Although 5-Hydroxytryptamine (5-HT) indirectly stimulates muscle contraction and participates in regulating Acetylcholine receptor (AChR) cluster homeostasis in cellular, animal, and clinical studies, evidence regarding its potential to modulate muscle contraction in myasthenia gravis (MG) remains limited. We aim to determine the levels of 5-HT in MG and investigate its potential role as a regulatory neurotransmitter in promoting muscle contraction.</p><p><strong>Methods: </strong>We collected serum from 109 patients with MG and 110 healthy volunteers, and recorded clinical variables, including myasthenia gravis classification (MGFA), quantitative myasthenia gravis score (QMG), and serological examination. The effects of 5-HT on the neuromuscular junction (NMJ) were further identified using cellular and molecular experiments.</p><p><strong>Results: </strong>In this study, we observed that serum 5-HT levels decrease in patients with MG (p < 0.0001) compared with disease-free control. The thymoma-associated complications alleviated this reduction (p < 0.0001). Our functional studies showed that 5-HT promotes the development of motor (cholinergic) neuron-like axons and increases intracellular calcium peaks, which is proportional to the amount of neurotransmitter released (p < 0.0001). AChR-autoantibody treatment increases the expression of 5-HT₂R mRNA in muscle tube cells (p < 0.001), and the downstream signaling pathway of 5-HT₂R is involved in the regulation of AChR cluster homeostasis.</p><p><strong>Interpretation: </strong>This first report of clinical characteristics and serum 5-HT levels from a cross-sectional cohort study on MG suggests that 5-HT plays a critical role in maintaining NMJ homeostasis. Additional cross-sectional data on more MG phenotypes and longitudinal monitoring data are needed to explore the role of 5-HT in the pathophysiological mechanisms of MG.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAB39B Related Parkinsonism in an Italian Family: A Unique Use of Advanced Therapies.","authors":"Caterina Del Regno, Giovanni Ermanis, Christian Lettieri, Andrea Bernardini, Gaia Pellitteri, Enrico Belgrado, Elena Betto, Gian Luigi Gigli, David De Monte, Marco Domenico Scanni, Marco Mucchiut, Giuseppe Damante, Mariarosaria Valente, Francesco Janes","doi":"10.1002/acn3.70225","DOIUrl":"https://doi.org/10.1002/acn3.70225","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder that may sometimes be caused by deleterious genetic variants. Among them, RAB39B polymorphisms are known as rare causes of early-onset PD associated with intellectual disability (Waisman's syndrome). Here we describe a 45-year-old white male affected by developmental delay, childhood onset intellectual disability, epilepsy, and PD who was treated with subthalamic deep brain stimulation and subcutaneous L-DOPA infusion. Next Generation Sequencing analysis revealed a currently unknown pathogenic hemizygous sequence variant c.463C>T (NM_171998.4) in the RAB39B gene, confirmed also in the proband's mother, affected by late-onset PD. This report expands the number of described RAB39B mutations in individuals with early- and late-onset, X-linked PD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}