Degenerative neurological and neuromuscular disease最新文献

{"title":"Agreement and Comparative Performance of Cognitive Testing, Visual MRI Rating, and Automated Brain Morphometry in Older Adults with Suspected Dementia in Uganda.","authors":"Rita Nassanga, Mark Kaddumukasa, Stephen E Jones, Martha Sajatovic, Ajay Nemani, Roy Clark Basiimwa, Michael Grace Kawooya, James K Tumwine, Kamada Lwere, Joy Louise Gumikiriza-Onoria, Aloysius Gonzaga Mubuuke, Noeline Nakasujja","doi":"10.2147/DNND.S590989","DOIUrl":"https://doi.org/10.2147/DNND.S590989","url":null,"abstract":"<p><strong>Background: </strong>Dementia diagnosis in sub-Saharan Africa is constrained by limited access to specialist neuroimaging interpretation and reduced specificity of brief cognitive tools in low-literacy populations. We evaluated the agreement, incremental value, and comparative performance of Mini Mental State Exam (MMSE), visual MRI medial temporal atrophy (MTA), and automated brain morphometry in older Ugandan adults with suspected dementia.</p><p><strong>Methods: </strong>In this cross-sectional study, adults aged ≥50 years with suspected dementia were recruited from neurology and psychiatry clinics at two hospitals and from a community cohort. Participants underwent MMSE and standardized 1.5T brain MRI. Visual MRI ratings were performed by radiologists blinded to clinical data, and automated morphometry was generated using NeuroQuant^® normative percentiles. Hippocampal occupancy (HOC <5th percentile) was used as a reference MRI biomarker for comparative classification. Agreement between visual and automated measures was assessed using Spearman correlation and intraclass correlation. Incremental value was assessed using regression models, and comparative performance using area under the curve (AUC).</p><p><strong>Results: </strong>Sixty-three participants were included (mean age 75.6 ± 8.7 years; 49 female). Agreement between visual ratings and automated morphometry was poor. MMSE correlated inversely with MTA (<i>ρ</i> = -0.47; p = 0.049) and correlated positively with hippocampal volume percentile (<i>ρ</i> = 0.46; p = 0.056). Adding hippocampal volume to MTA did not improve model fit for MMSE (ΔR² = 0.028; p = 0.18). For comparative classification, MMSE alone was sensitive but poorly specific, while the combined MMSE-MTA model improved specificity and discrimination (AUC 0.70 vs 0.62 for either measure alone).</p><p><strong>Conclusion: </strong>Visual and automated MRI measures were not interchangeable in this heterogeneous cohort. Automated hippocampal volumetry added limited value beyond visual MTA for global cognition, while combining MMSE with visual MTA showed modest improvement in comparative classification and warrants further validation.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"590989"},"PeriodicalIF":3.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Gut-Brain Axis in Alzheimer's: From Microbiota Genetics to Stigmasterol's Neuroprotection Mechanism.","authors":"Tunan Ding, Junlei Chen, Yunsheng Xiang, Xiaojie Zhou, Hongbo Zheng, Yihan Bai, Weihao Wang, Qiang Fu, Yan Chen, Yin Fu","doi":"10.2147/DNND.S580890","DOIUrl":"https://doi.org/10.2147/DNND.S580890","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to identify novel therapeutic targets for Alzheimer's disease (AD) by investigating the role of the intestinal flora (IF) via the gut-brain axis, and to predict a potential natural compound for AD treatment and elucidate its underlying mechanism.</p><p><strong>Methods: </strong>Following a primary analytical axis, we first employed Mendelian randomization (MR) to infer causal relationships between gut microbiota and AD. To pinpoint molecular targets, we integrated Summary-data-based MR (SMR) with single-cell and spatial transcriptomics. Subsequently, network pharmacology and molecular docking were used to identify stigmasterol as a candidate compound targeting the causal pathway. Finally, the neuroprotective effects and the STIM1/Orai1-mediated mechanism were experimentally validated in vitro using Aβ_1-42 exposed SH-SY5Y cells.</p><p><strong>Results: </strong>MR-based causal inference identified Desulfovibrio as a risk factor for AD, while Slackia and the Lachnospiraceae NK4A136 group were protective factors. Seven key AD-related genes were identified by combining MR results with databases, which were highly druggable. SMR analysis and multi-omics integration pinpointed STIM1-mediated calcium signaling as the core causal pathway. Following the identification of stigmasterol via network pharmacology and molecular docking, in vitro experimental validation confirmed that stigmasterol significantly inhibited Aβ_1-42 induced neuronal apoptosis and calcium overload by specifically modulating the STIM1/Orai1 pathway and the Bcl-2/Bax ratio.</p><p><strong>Conclusion: </strong>This study decodes the gut-brain axis by establishing the specific causal pathway. We demonstrate that Stigmasterol exerts neuroprotective effects by inhibiting apoptosis through a IF-associated mechanism involving the STIM1/Orai1 pathway, provideing novel insights into AD pathogenesis and offering a promising therapeutic strategy based on natural compounds.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"580890"},"PeriodicalIF":3.2,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Siponimod with Up to 2 Years of Treatment in a Real-World Setting in People with SPMS: Analysis from the Novartis Global Managed Access Program.","authors":"Antonio Carotenuto, Dimitris Naoumis, Vincenzo Brescia Morra, Evangelos Kouremenos, Suzannah Hetherington, Sophie Arnould, Virginia de Las Heras","doi":"10.2147/DNND.S540207","DOIUrl":"10.2147/DNND.S540207","url":null,"abstract":"<p><strong>Background: </strong>Limited real-world data exist on the effectiveness of siponimod in people living with secondary progressive multiple sclerosis (plwSPMS).</p><p><strong>Objective: </strong>To analyze the real-world data of patients receiving siponimod under a managed access program (MAP).</p><p><strong>Methods: </strong>The MAP was implemented in countries where siponimod was not approved and provision via MAP was permitted under local regulations. Data on the demographic/clinical characteristics and clinical outcomes of the cohort included in this MAP between February 2019 and April 2022, were collected from physicians using a Novartis database.</p><p><strong>Results: </strong>Among patients with evidence of starting siponimod treatment in the MAP (n=516), the mean EDSS at baseline was 5.2. Among those with post-baseline data available (n=423), the mean change from baseline in EDSS score at month 6 was -0.04 (95% confidence interval [CI]: -0.10, 0.01) and 0.03 (95% CI: -0.03, 0.10) at month 24), and the annual relapse rate was 0.023. Cognition was stable or improved in patients for whom data was available. Among patients with ≥1 MRI assessment (n=165), 154 (93.3%) had no findings of disease activity.</p><p><strong>Conclusion: </strong>This real-world data set analysis provides data on the demographic/clinical characteristics of plwSPMS taking siponimod in clinical practice under MAP criteria and on the effectiveness that can be attained.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"540207"},"PeriodicalIF":3.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emodin, a Phytotherapeutic Anthraquinone, Potently Attenuates Synaptic Redox Pathology in Aged Rats.","authors":"Priyanka Saha, Faraz Ahmad","doi":"10.2147/DNND.S570320","DOIUrl":"10.2147/DNND.S570320","url":null,"abstract":"<p><strong>Background: </strong>Aging is associated with increased oxidative stress, which leads to synaptic vulnerability and psychiatric and cognitive deficits. Maintaining redox homeostasis is crucial for synaptic health. However, age-related alterations in synapse-specific antioxidant capacity remain poorly understood. Moreover, effective therapeutic strategies to counteract these changes are lacking. This study aimed to assess redox parameters in ex vivo synaptic terminals from young and old rat brains and evaluate the modulatory effects of the phytotherapeutic compound emodin.</p><p><strong>Methods: </strong>Brain synaptosomes were isolated from young and old male Wistar rats. The antioxidant capacities were determined using 2,2'-azinobis-[3-ethylbenzothiazoline-6-sulfonic acid] (ABTS) and ferric-reducing antioxidant power (FRAP) assays. Oxidative stress and damage were assessed by quantifying reactive oxygen species (ROS) and nitrogen species (RNS) and examining oxidative modifications of proteins and lipids. The antioxidant effects of emodin were investigated in mitigating synaptic oxidative stress and damage.</p><p><strong>Results: </strong>A significant decline in antioxidant capacity and increase in ROS levels were observed in the synaptosomes of aged animals. Oxidative damage was also evident as increased protein carbonylation, thiol oxidation, and lipid peroxidation. Emodin treatment improved redox balance by reducing ROS levels, decreasing oxidative damage markers, and enhancing antioxidant defenses, particularly in older animals.</p><p><strong>Conclusion: </strong>Aging disrupts synaptic redox homeostasis and increases the susceptibility to oxidative damage. Emodin exerts protective antioxidant effects by mitigating oxidative stress and enhancing the redox capacity of the synaptosomes. These findings suggest that emodin may have therapeutic potential in preserving synaptic function under conditions of age-related oxidative stress, although further functional and molecular studies are warranted to validate its neuroprotective efficacy.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"570320"},"PeriodicalIF":3.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Spectrum and Phenotypic Variability in Chinese Patients with Multisystem Proteinopathy and Related Disorders.","authors":"Xingyu Xia, Xi Chen, Yiming Sun, Ming Zhang, Kai Qiao, Yan Chen, Chongbo Zhao, Yi Dong, Wenhua Zhu","doi":"10.2147/DNND.S568971","DOIUrl":"https://doi.org/10.2147/DNND.S568971","url":null,"abstract":"<p><strong>Objective: </strong>Multisystem proteinopathy (MSP) is a pleiotropic group of disorders initially presenting as inclusion body myopathy (IBM), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and/or Paget disease of bone (PDB). Additional genes including <i>MATR3, OPTN</i>, and <i>ANXA11</i>, have recently been implicated in MSP-like disorders, further expanding the genetic spectrum. This research aims to study the genetic and clinical characteristics of MSP and related disorders in a large Chinese cohort.</p><p><strong>Methods: </strong>Twenty-nine patients were identified in 953 patients diagnosed with ALS, IBM, or dementia at Huashan Hospital between 2000 and 2024. Variants in MSP-related genes were detected using next-generation sequencing and confirmed by Sanger sequencing. Clinical, pathological, imaging, and electromyography data were collected and analyzed.</p><p><strong>Results: </strong>A total of 29 patients (3.0%) were identified as carrying MSP-related gene variants. Most patients were male (72.4%), with disease onset predominantly in the third to fifth decades of life. The majority of patients (21/29) presented with a single clinical phenotype. ALS was the most common phenotype (20/29), followed by IBM (10/29), FTD (7/29), and PDB (1/29). The most frequent variants were in <i>ANXA11</i> (34.5%) and <i>VCP</i> (20.7%), followed by <i>OPTN</i> (17.2%),<i> SQSTM1</i> (10.3%), <i>MATR3</i> (10.3%), and <i>HNRNPA1</i> (6.9%). All patients with <i>VCP</i> variants presented with initial lower limb involvement, whereas those carrying <i>ANXA11</i> or <i>OPTN</i> variants predominantly showed upper limb or bulbar onset. Patients harboring <i>OPTN</i> variants had a later age at onset compared with those carrying <i>VCP</i> or <i>MATR3</i> variants. Patients with ALS-onset exhibited faster progression compared with those with myopathy-onset, even when harboring identical variants.</p><p><strong>Conclusion: </strong>This study broadens the clinical and genetic landscape of MSP and related disorders in a Chinese cohort. These results emphasize the clinical utility of next-generation sequencing for improving diagnostic accuracy in patients with unexplained neuromuscular or cognitive presentations, especially in the presence of multisystem involvement.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"568971"},"PeriodicalIF":3.2,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Therapy for Alzheimer's Disease Based on the Cerebral Lymphatic System.","authors":"Feiyue Mi, Li Ren, Dongfeng Pan, Changyin Yu","doi":"10.2147/DNND.S574901","DOIUrl":"10.2147/DNND.S574901","url":null,"abstract":"<p><strong>Background: </strong>Conventional therapeutic interventions for Alzheimer's disease (AD) are limited by multiple drawbacks, including anticholinesterase inhibitors, glutamate receptor antagonists, intestinal flora regulators and Aβ-targeting monoclonal antibodies, which only achieve modest symptomatic relief, are accompanied by notable adverse events (e.g., intracerebral hemorrhage, cerebral edema) and have suboptimal clinical efficacy. In recent years, the cerebral lymphatic system, consisting of the glial lymphatic system (GLS) and meningeal lymphatic vessels (MLVs), has been identified as a key mediator of amyloid β-protein (Aβ) clearance and a critical driver of AD pathogenesis. Lymphatic dysfunction in this system precedes and exacerbates Aβ deposition and cognitive decline in AD patients, revealing the close association between cerebral lymphatic system impairment and AD progression.</p><p><strong>Purpose: </strong>This study aims to focus on the emerging therapeutic advancements for AD targeting the cerebral lymphatic system, moving beyond the conventional symptomatic treatments and Aβ-centric interventions. It also intends to systematically summarize the relevant mechanisms of the cerebral lymphatic system in AD and the diverse therapeutic strategies targeting this system, thus providing a framework for developing innovative clinical interventions for AD.</p><p><strong>Methods: </strong>This study adopted a review approach, systematically collating and analyzing existing research on the cerebral lymphatic system and AD, including the cerebral lymphatic pathway of Aβ clearance, the pathological consequences of lymphatic impairment in AD, and various therapeutic strategies targeting the cerebral lymphatic system that have been reported in current studies.</p><p><strong>Results: </strong>The review identified and summarized multiple categories of effective therapeutic strategies targeting the cerebral lymphatic system for AD, covering pharmacological agents (VEGF-C, traditional Chinese medicines, oxytocin), photobiotherapies (808 nm near-infrared light, 40 Hz multisensory stimulation), physiotherapies (aerobic exercise, rTMS), gene therapy (DSCR1 upregulation), and surgical interventions (lymphatic-venous anastomosis). All these strategies are designed to optimize cerebral lymphatic function and thereby enhance Aβ drainage in the brain.</p><p><strong>Conclusion: </strong>Optimizing cerebral lymphatic function to enhance Aβ drainage is a viable, disease-modifying therapeutic direction for AD. This therapeutic approach targeting the cerebral lymphatic system can serve as a complementary or alternative method to current symptomatic or Aβ-targeted treatments for AD, and also provides a theoretical and practical framework for the development of innovative clinical interventions for the disease.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"574901"},"PeriodicalIF":3.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Identification of ALDOA as a Pathogenic TDP-43 Interaction Partner in ALS.","authors":"Kaixin Yan, Jinfeng Deng, Yuxuan Yong, Fangfang Bi","doi":"10.2147/DNND.S535954","DOIUrl":"10.2147/DNND.S535954","url":null,"abstract":"<p><strong>Objective: </strong>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons, and its pathogenesis has not been fully elucidated. TAR DNA-binding protein 43 (TDP-43), as one of the key pathogenic genes in ALS, participates in the disease process through interactions with various proteins. This study aims to investigate the interaction mechanism between TDP-43 and aldolase A (ALDOA) in ALS.</p><p><strong>Methods: </strong>HEK293T cell models transfected with wild-type and mutant TDP-43 (TDP-43^M337V) plasmids were constructed. The interaction between TDP-43 and ALDOA was analyzed through proteomic screening of specific peptides and co-immunoprecipitation, and the co-localization of the two in cells was detected by immunofluorescence. Changes in ALDOA expression levels after intervention with mutant TDP-43 were detected by Western blot and quantitative real-time PCR.</p><p><strong>Results: </strong>Proteomic analysis identified ALDOA as a potential interacting protein of TDP-43. Protein-protein interaction (PPI) analysis, co-immunoprecipitation, and immunofluorescence experiments further confirmed that both wild-type and mutant TDP-43 interact with ALDOA. Western blot and quantitative real-time PCR results showed that, compared with the wild-type TDP-43 group, the ALDOA expression was significantly increased in the TDP-43^M337V mutant group.</p><p><strong>Conclusion: </strong>TDP-43 interacts with ALDOA in ALS, and the TDP-43^M337V mutation significantly promotes ALDOA expression, suggesting that ALDOA may be involved in the pathogenesis of TDP-43-mediated ALS. These findings provide new insights into the pathogenesis of ALS and highlight a potential therapeutic target.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"15 ","pages":"123-132"},"PeriodicalIF":3.2,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case Report and Literature Review of Charcot-Marie-Tooth Disease Type 2F in a Family.","authors":"Yanli Lei, Li Cheng, Weijing Zhao, Pengfei Che, Xue Dong, Lei Ma","doi":"10.2147/DNND.S539370","DOIUrl":"10.2147/DNND.S539370","url":null,"abstract":"<p><strong>Objective: </strong>To report the clinical and genetic characteristics of a rare Charcot-Marie-Tooth disease type 2F (CMT2F) pedigree, and to explore the phenotypic diversity and diagnostic essentials of the mutation in combination with literature review.</p><p><strong>Methods: </strong>The clinical data, electrophysiological findings, and genetic testing results of the proband and pedigree members were retrospectively analyzed, and relevant literatures were reviewed for comparative analysis.</p><p><strong>Results: </strong>Both patients had an onset in middle and old age (50/66 years), presenting with distal lower limb muscle weakness (Grade III), muscle atrophy, absent tendon reflexes, pes cavus, and sensory abnormalities. Serum creatine kinase (CK) was elevated (474 U/L), and electromyography indicated axonal peripheral nerve damage. Genetic testing revealed a heterozygous mutation of HSPB1 gene c.418C>G [p.Arg140Gly], which was verified by co-segregation in the pedigree. Literature review showed that this mutation causes axonal transport dysfunction by impairing the chaperone function of HSP27.</p><p><strong>Conclusion: </strong>This study expands the phenotypic spectrum of late-onset CMT2F, with some patients showing mild elevation of serum CK. It provides new clinical evidence for the pathogenicity of this mutation.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"15 ","pages":"117-122"},"PeriodicalIF":3.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12554951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Symptom Networks and Associations with Quality of Life in Patients with Early to Mid-Stage Parkinson's Disease: A Network Analysis.","authors":"Qiu Deng, Yaoling Duan, Zhengting Yang, Puqing Wang, Ziwei Liu, Min Zhou","doi":"10.2147/DNND.S535306","DOIUrl":"10.2147/DNND.S535306","url":null,"abstract":"<p><strong>Purpose: </strong>The symptoms of patients with early to mid-stage Parkinson's disease (PD) are closely associated with their quality of life. However, few studies have explored the relationship between symptoms and quality of life. This study aims to investigate the symptom profiles of patients with early to mid-stage PD, construct a symptom network to identify core symptoms, and examine their associations with quality of life.</p><p><strong>Patients and methods: </strong>This cross-sectional study was conducted from November 2024 to February 2025 among 954 patients with early to mid-stage PD in China, with stages 1-2 classified as early stage and stage 3 as mid stage. All participants completed the PD Symptom Experience Scale. Network models were constructed using R version 4.4.3 to identify core symptoms, describe inter-symptom relationships, and calculate centrality indices.</p><p><strong>Results: </strong>The top three symptoms in terms of prevalence were bradykinesia (77.46%), resting tremor (75.05%), and rigidity (59.01%). The most severe symptom was resting tremor. In the symptom network analysis, the top three symptoms with the highest node centrality were bradykinesia (r_e=1.27), postural instability (r_e=1.16), and limb stiffness (r_e=1.96). In the quality of life network, the dimensions with the highest node centrality were \"mobility\" (r_be=0.52), \"emotional well-being\" (r_be=0.50), and \"cognitions\" (r_be=0.49). \"Mobility\" was positively correlated with difficulty turning over in bed (r=0.19), freezing of gait (r=0.09), and difficulty standing up or sitting down (r=0.08).</p><p><strong>Conclusion: </strong>Multiple symptoms were simultaneously experienced by patients with early to mid-stage PD, and interrelationships among symptoms were observed. Bradykinesia was identified as the core symptom, and the \"mobility\" dimension was recognized as the central node in the quality of life network. Healthcare providers are advised to comprehensively consider patients' overall symptom profiles and their relationships with quality of life, and to implement targeted, integrated interventions.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"15 ","pages":"101-116"},"PeriodicalIF":3.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyotrophic Lateral Sclerosis Masquerading as Multiple System Atrophy with Parkinsonism and Anxiety as Initial Manifestations.","authors":"Haiyan Tang, Jianping Yao, Zhuang Wang","doi":"10.2147/DNND.S531647","DOIUrl":"10.2147/DNND.S531647","url":null,"abstract":"<p><strong>Introduction: </strong>Amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) are both neurodegenerative disorders. While ALS may present with clinical features resembling Parkinsonism, there have been no definitive reports of ALS mimicking MSA, only cases of Primary lateral sclerosis (PLS) mimicking Parkinsonism.</p><p><strong>Methods: </strong>This article reports a case of ALS presenting with Parkinsonism and anxiety as the initial symptoms. Five years after the initial diagnosis of MSA, the patient developed signs of lower motor neuron involvement, including fasciculations and muscle atrophy, ultimately leading to a revised diagnosis of ALS. This study combines literature analysis to explore the reasons for misdiagnosis and identifies key differentiating features.</p><p><strong>Results: </strong>Specifically, muscle rigidity in ALS is characterized by a velocity-dependent increase in muscle tone caused by damage to the upper motor neurons. This symptom tends to be more pronounced in the lower limbs than in the upper limbs and is often accompanied by spastic gait. Objective examinations may reveal early atrophy of the frontal and temporal lobes of the cerebrum on head magnetic resonance (MR) imaging, whereas ¹⁸F-FDG brain positron emission tomography (PET) may reveal reduced metabolism in the frontal and parietal lobes of the cerebrum with normal basal ganglial function, distinguishing ALS from basal ganglial metabolic decline in MSA.</p><p><strong>Discussion: </strong>To our knowledge, this is the first case of ALS misdiagnosed as MSA. Clinically, patients with parkinsonism who do not respond to dopaminergic drugs should be cautious about atypical ALS. Muscle rigidity manifesting as upper motor neuron damage, and MR and ¹⁸F-FDG brain PET imaging can provide early differential diagnosis indicators.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"15 ","pages":"95-100"},"PeriodicalIF":3.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}