Journal of Neurology最新文献

{"title":"Neurological disability and brain grey matter atrophy in primary progressive multiple sclerosis are determined by microstructural lesional changes, but not by lesion load.","authors":"Theodoros Ladopoulos, Zainab Abbas, Britta Krieger, Barbara Bellenberg, Jeyanthan Charles James, Jana Bauer, Ralf Gold, Carsten Lukas, Ruth Schneider","doi":"10.1007/s00415-025-13043-x","DOIUrl":"10.1007/s00415-025-13043-x","url":null,"abstract":"<p><strong>Background: </strong>Conventional MRI measures, such as the number and volume of MS lesions, are histologically non-specific and cannot sufficiently explain clinical disability or brain atrophy in MS. Nevertheless, demyelinating plaques exhibit distinct histopathological features in relapsing and progressive multiple sclerosis (MS) subtypes. The aim of this study was to assess microstructural characteristics of MS lesions using quantitative MRI and explore their associations with grey matter (GM) atrophy and clinical disability.</p><p><strong>Methods: </strong>56 control subjects (CS), 121 patients with relapsing-remitting (RRMS), and 38 patients with primary progressive MS (PPMS) underwent 1.5 T MRI scans and clinical examinations. Lesion and brain segmentation based on T1-weighted and FLAIR images were performed using SAMSEG. The MDME sequence and SyMRI software were used to estimate relaxation rates and myelin volume fraction in MS lesions and normal-appearing white matter (NAWM). Associations between quantitative lesional and NAWM MRI parameters with GM atrophy and clinical disability were investigated.</p><p><strong>Results: </strong>Brain regional volumes and quantitative lesional and NAWM MRI parameters were significantly decreased in patients with PPMS compared to those with RRMS. Quantitative lesional MRI parameters demonstrated statistically significant associations with cortical and deep GM volumes as well as with disability scores in RRMS and especially in PPMS. In contrast to RRMS, lesion volume was not associated with either GM atrophy or clinical disability in the PPMS group.</p><p><strong>Conclusions: </strong>Quantitative lesional MRI measures, but not lesion load, were strongly associated with clinical disability and GM atrophy in PPMS patients, likely reflecting differences in lesion pathology between MS subtypes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"302"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753123","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":"Natural history of adult-onset metachromatic leukodystrophy.","authors":"Daniele Mandia, Juliette Dufour, Silvia Fenu, Ettore Salsano, Chiara Benzoni, François Sellal, Jeremie Pariente, Nilgün Cengiz, Magali Pettazzoni, Thierry Levade, Foudil Lamari, Catherine Caillaud, Roberta La Piana, David Brassat, Françoise Durand-Dubief, Gérard Besson, Sylvie Odent, David Devos, Mélanie Barbay, Maria Makrygianni, Hojka Gregoric Kumperscak, Roseline Froissart, Yann Nadjar","doi":"10.1007/s00415-025-12997-2","DOIUrl":"10.1007/s00415-025-12997-2","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"303"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753120","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":"Exploring epigenetic modifications as potential biomarkers and therapeutic targets in amyotrophic lateral sclerosis.","authors":"XiaoTong Hou, JingSi Jiang, Min Deng","doi":"10.1007/s00415-025-13028-w","DOIUrl":"https://doi.org/10.1007/s00415-025-13028-w","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. Whole-genome sequencing has identified many novel ALS-associated genes, but genetics alone cannot fully explain the onset of ALS and an effective treatment is still lacking. Moreover, we need more biomarkers for accurate diagnosis and assessment of disease prognosis. Epigenetics, which includes DNA methylation and hydroxymethylation, histone modifications, chromatin remodeling, and non-coding RNAs, influences gene transcription and expression by affecting chromatin accessibility and transcription factor binding without altering genetic information. These processes play a role in the onset and progression of ALS. Epigenetic targets can serve as potential biomarkers and more importantly, the reversibility of epigenetic changes supports their potential role as versatile therapeutic targets in ALS. This review summarized the alterations in different epigenetic modulations in ALS. Additionally, given the close association between aberrant metabolic profiles characterized by hypoxia and high glycolytic metabolism in ALS and epigenetic changes, we also integrate epigenetics with metabolomics. Finally, we discuss the application of therapies based on epigenetic mechanisms in ALS. Our data integration helps to identify potential diagnostic and prognostic biomarkers and support the development of new effective therapies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"304"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764123","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":"Alexander Ecker (1816-1887).","authors":"Andrew J Larner","doi":"10.1007/s00415-025-13038-8","DOIUrl":"https://doi.org/10.1007/s00415-025-13038-8","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"301"},"PeriodicalIF":4.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753118","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 disease-specific structural pattern in Parkinson's disease and its cortical characteristics associated with gene function: a 7-Tesla MRI study.","authors":"Xiaoyu Wang, Yongqin Xiong, Caohui Duan, Jianxing Hu, Haoxuan Lu, Mingliang Yang, Jiayu Huang, Yan Li, Zhixuan Li, Song Wang, Miao Wang, Xi Yin, Jing Zhao, Zhongbao Gao, Xin Lou","doi":"10.1007/s00415-025-13035-x","DOIUrl":"https://doi.org/10.1007/s00415-025-13035-x","url":null,"abstract":"<p><p>Brain structure characteristics form the basis on regulating neuroplastic processes by genes, and structural alterations may contribute to the progression of Parkinson's disease (PD) and their divergent clinical manifestations. However, the neural mechanisms underlying the relations between the genetic signatures to structural alterations in PD patients are unclear. This study aimed to integrate alterations in cortical thickness and subcortical nuclei volume (thalamus, hippocampus, and amygdala) in PD, and to explore global cortical thickness differences associated with gene function. 7-Tesla magnetic resonance imaging scans were obtained for 98 patients with PD and 74 healthy controls (HC). Cortical thickness and subcortical nuclei volume were extracted based on FreeSurfer and were analyzed using general linear model to find significant differences between two groups. Regression model was used for cross-sectional the impact of structural alterations on motor signs as well as non-motor symptoms. Gene-imaging association analysis was used to characterize its gene signatures. Compared with HC, PD patients exhibited the disease-specific structural pattern, characterized by reduced cortical thickness in the right pars triangularis and altered volumes of specific nuclei subfields. Moreover, the Cornu Ammonis 1 head volume was significantly correlated with rigidity scores. Using human brain gene expression data, genes identified in this study were enriched for ribosome and synaptic organization and explain significant variation in global cortical thickness differences. Taken together, these findings may contribute to a better understanding of neural mechanisms in PD and the functional roles of genes that influence brain structure.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"300"},"PeriodicalIF":4.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753130","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":"PRNP E146G mutation inherited prion disease: distinctive clinical, pathological and fluid biomarker features.","authors":"Thomas Coysh, Zane Jaunmuktane, Laszlo L P Hosszu, Nour Majbour, Fuquan Zhang, Tracy Campbell, Lee Darwent, Marcelo Barria Matus, Edgar Chan, Leah Holm-Mercer, Tze How Mok, Jonathan D F Wadsworth, Jan Bieschke, Kannan Nithi, Sebastian Brandner, Colin Smith, Margaret Esiri, John Collinge, Simon Mead","doi":"10.1007/s00415-025-13022-2","DOIUrl":"10.1007/s00415-025-13022-2","url":null,"abstract":"<p><p>Inherited prion diseases (IPDs) are phenotypically diverse neurodegenerative conditions caused by mutations in the prion protein gene (PRNP). We describe IPD due to a novel PRNP E146G mutation in a 50-year-old man presenting with slowly progressive dysarthria, prominent myoclonus especially in the lower limbs, and less prominent gait ataxia, pyramidal and extrapyramidal signs. Cognitive impairment was not overt at disease onset. MRI revealed cerebellar atrophy and white matter hyperintensities. His 46-year-old sister carries the mutation and has subtle gait ataxia and dysarthria. Both patients exhibit a distinctive fluid biomarker profile: in CSF S100B is > twofold upper limit of normal, total tau is moderately elevated, and neurofilament light chain, 14-3-3 and RT-QuIC are negative; in plasma there is marked elevation of GFAP but repeatedly normal neurofilament light chain. The proband's father died aged 55 following an 8-year dementing illness with similar presentation. Post-mortem revealed cerebellar cortical atrophy and profuse large PrP amyloid plaques across cerebral and cerebellar grey matter. Immunoblotting identified low molecular weight protease-resistant PrP fragments. E146G mutation IPD broadly fits into the historical Gerstmann-Sträussler-Scheinker disease spectrum but, based on deep clinical phenotyping of this initial pedigree, we highlight some distinctive features, which may aid in identification of this disease.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"299"},"PeriodicalIF":4.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742959","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":"Wolfgang Zeman (1921-2001).","authors":"Lazaros C Triarhou","doi":"10.1007/s00415-025-13040-0","DOIUrl":"https://doi.org/10.1007/s00415-025-13040-0","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"298"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743015","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":"Jans Muller (1930-2013).","authors":"Lazaros C Triarhou","doi":"10.1007/s00415-025-13041-z","DOIUrl":"https://doi.org/10.1007/s00415-025-13041-z","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"295"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730420","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 association between non-motor symptoms and cost in Parkinson's disease.","authors":"Anna Gustafsson, Frida Hjalte, Jenny Norlin, Per Odin, Peter Hagell","doi":"10.1007/s00415-025-13044-w","DOIUrl":"10.1007/s00415-025-13044-w","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a neurodegenerative disorder associated with substantial costs that escalate as the disease progresses. Previous research has explored the relationship between disease progression, motor symptoms, and the economic burden of PD. However, there is a lack of studies focusing on the relationship between costs and non-motor symptoms (NMS).</p><p><strong>Objective: </strong>To examine the association between societal costs and NMS in individuals with PD in Sweden.</p><p><strong>Methods: </strong>Persons with idiopathic PD in the Swedish Parkinson's disease registry from the region of Skåne with registrations of non-motor symptoms questionnaire (NMSQ) were included. Identified subjects were linked to administrative health care data registries, to estimate annual costs. A generalized linear model was used to assess the relationship between NMS and costs.</p><p><strong>Results: </strong>NMS were present in 74% (n = 703) of the study population, with a mean of 6.9 symptoms per observation. The number of NMS increased with disease duration, and costs were higher for those with a greater number of symptoms. Formal care costs were 3.8 times higher in observations with at least 10 NMS. Experiencing hallucinations and/or delusions was associated with an 80-94% increase in total costs, corresponding to an additional SEK 107,000-121,000 per patient year.</p><p><strong>Conclusions: </strong>Presence of NMS in PD is associated with substantial societal costs. Findings from this study highlight the necessity for comprehensive management strategies that address both motor and non-motor symptoms to potentially alleviate the burden on patients and the healthcare system.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"297"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735953","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":"The effects of dopaminergic medication and task load on trembling and akinetic freezing of gait in Parkinson's disease.","authors":"Demi Zoetewei, Pieter Ginis, Talia Herman, Moran Gilat, Nicholas D'Cruz, Luca Palmerini, Eran Gazit, Jeffrey M Hausdorff, Alice Nieuwboer","doi":"10.1007/s00415-025-13023-1","DOIUrl":"https://doi.org/10.1007/s00415-025-13023-1","url":null,"abstract":"<p><strong>Background: </strong>In people with Parkinson's disease (PD), freezing of gait (FOG) can manifest as an absence of leg movement (akinetic) or a presence of high-frequency leg trembling. FOG is triggered most often during turning or dual-tasking when OFF-medication, but it is unclear whether the same holds true for akinetic and trembling FOG.</p><p><strong>Objectives: </strong>To investigate the effects of dopaminergic medication and cognitive and motor tasks on trembling and akinetic FOG.</p><p><strong>Method: </strong>Sixty-three PD patients with daily FOG performed a home-based FOG-provoking protocol OFF and ON-dopaminergic medication. FOG was video-annotated based on pre-specified definitions. We compared the % time in trembling and in akinetic FOG between OFF and ON. We also analyzed these outcomes during various motor tasks and with- and without a cognitive dual task. To identify subgroups, an exploratory k-means cluster analysis was performed.</p><p><strong>Results: </strong>Trembling and akinetic FOG co-occurred in most patients (82.5%), although trembling was observed most frequently. Both manifestations were ameliorated by medication, but we identified four different patterns: a responsive mild group (n = 32), an unresponsive akinetic-dominant group (n = 8), and two trembling-dominant groups with (n = 12) and without (n = 11) a response to medication. Task load also affected the manifestations differentially, as dual-tasking and gait initiation induced more akinetic FOG compared to other conditions.</p><p><strong>Conclusions: </strong>Trembling and akinetic FOG respond similarly to dopaminergic medication (except for a specific trembling subgroup), yet they are differentially influenced by FOG triggers. Altogether, we suggest that \"trembling\" may represent a milder form of FOG, although \"trembling\" as a distinct FOG-variant cannot be rule out.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"296"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735955","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}