Journal of Neurology最新文献

{"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":"https://doi.org/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":"","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":"","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}

{"title":"Analysis of C9orf72 repeat length in progressive supranuclear palsy, corticobasal syndrome, corticobasal degeneration, and atypical parkinsonism.","authors":"David P Vaughan, Raquel Real, Marte Theilmann Jensen, Riona G Fumi, Megan Hodgson, Edwin Jabbari, Danielle Lux, Lesley Wu, Thomas T Warner, Zane Jaunmuktane, Tamas Revesz, James B Rowe, Jonathan Rohrer, Huw R Morris","doi":"10.1007/s00415-025-12990-9","DOIUrl":"10.1007/s00415-025-12990-9","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic hexanucleotide repeat expansions in C9orf72 are the commonest genetic cause of frontotemporal dementia and/or amyotrophic lateral sclerosis. There is growing interest in intermediate repeat expansions in C9orf72 and their relationship to a wide range of neurological presentations, including Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, and corticobasal syndromes.</p><p><strong>Aims: </strong>To assess the prevalence of intermediate C9orf72 repeat expansions in a large cohort of prospectively-recruited patients clinically diagnosed with progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and atypical parkinsonism (APS), compared with healthy controls. We also sought to replicate the association between C9orf72 repeat length and CBD in neuropathologically confirmed cases.</p><p><strong>Methods: </strong>626 cases, including PSP (n = 366), CBS (n = 130), and APS (n = 53) from the PROSPECT study, and 77 cases with pathologically confirmed CBD were screened for intermediate repeat expansions in C9orf72 using repeat-primed PCR. These were compared to controls from the PROSPECT-M-UK study and from the 1958 Birth Cohort.</p><p><strong>Results: </strong>There was no difference in the mean or largest allele size in any affected patient group compared with controls. A higher proportion of our affected cohort had large C9orf72 repeat expansions compared to controls, but there was no difference when comparing the frequency of intermediate expansions between affected patients and controls. There was no relationship between repeat length and age at onset, level of disability, or survival.</p><p><strong>Conclusions: </strong>Intermediate expansions in C9orf72 do not appear to be a genetic risk factor for PSP, CBS, CBD, or atypical parkinsonism. They are not associated with age at onset, disability, or survival in our study.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"293"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730394","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":"MS treatment trends before, during, and after the COVID-19 pandemic: insights from the German MS Register.","authors":"Agni-Maria Konitsioti, Sarah Laurent, David Ellenberger, Alexander Stahmann, Paulus Rommer, Judith Haas, Clemens Warnke","doi":"10.1007/s00415-025-13010-6","DOIUrl":"10.1007/s00415-025-13010-6","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic affected healthcare management for people with multiple sclerosis (PwMS), leading to alterations in disease-modifying therapies (DMTs) due to concerns about COVID-19 outcomes and vaccine efficacy.</p><p><strong>Objectives: </strong>To compare DMT prescription patterns in PwMS before, during, and after the COVID-19 pandemic.</p><p><strong>Methods: </strong>PwMS from the German MS Register, between 2019 and 2024, either newly diagnosed (Cohort A) or who discontinued or switched DMT (Cohort B), were analyzed over a follow-up period of 3 months. Data from the pre-pandemic period were compared to early-, late-, and post-pandemic periods. DMTs were categorized as medium efficacy (meDMT) or high efficacy (heDMT).</p><p><strong>Results: </strong>In Cohort A (n = 1810), pre-pandemic 46% had no DMT within 3 months of diagnosis, 39% received meDMT, and 15% heDMT (7.5% B cell-depleting therapies (BCD)). heDMT use increased during later periods (\"early\" 19%, \"late\" 29%, \"post\" 41%), with a shift toward BCD. In cohort B (n = 4246), pre-pandemic 47% paused DMT, 19% switched to meDMT, and 34% to heDMT (17% BCD). heDMT use also rose during the pandemic (\"early\" 37%, \"late\" 47%, \"post\" 48%), with increased BCD use.</p><p><strong>Conclusions: </strong>There were no delays in DMT initiation or resumption during the pandemic with a notable increase in heDMT and BCD use, reflecting growing confidence in these treatment options.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"294"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730471","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":"Ray S. Snider (1911-1991).","authors":"Lazaros C Triarhou","doi":"10.1007/s00415-025-13017-z","DOIUrl":"https://doi.org/10.1007/s00415-025-13017-z","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"290"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710108","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":"Cerebellar dysfunction in frontotemporal dementia: intra-cerebellar pathology and cerebellar network degeneration.","authors":"Jana Kleinerova, Marlene Tahedl, Mary Clare McKenna, Angela Garcia-Gallardo, Siobhan Hutchinson, Orla Hardiman, Cédric Raoul, Fabrice Ango, Bernard Schneider, Pierre-Francois Pradat, Ee Ling Tan, Peter Bede","doi":"10.1007/s00415-025-13046-8","DOIUrl":"10.1007/s00415-025-13046-8","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share overlapping clinical, genetic, and neuroimaging features; a spectrum of conditions commonly referred to as the ALS-FTD continuum. The majority of imaging studies focus on supratentorial pathology, and phenotype-defining motor, cognitive, and behavioural profiles are often exclusively attributed to supratentorial degeneration overlooking the contribution of cerebellar pathology.</p><p><strong>Methods: </strong>A multimodal neuroimaging study was conducted to evaluate phenotype-associated cerebello-cerebral connectivity profiles in ALS-FTD, behavioural variant frontotemporal dementia (bvFTD), non-fluent variant (nfvPPA), and semantic variant primary progressive aphasia (svPPA). Structural connectivity, functional connectivity, and volumetric analyses were conducted.</p><p><strong>Results: </strong>Radial diffusivity analyses detected impaired bilateral cerebello-frontal, cerebello-parietal, and cerebello-temporal connectivity in all study groups along the ALS-FTD spectrum. Cerebello-occipital disconnection was captured in ALS-FTD and nfvPPA. Spinocerebellar disconnection was detected in C9orf72 negative ALS-FTD and nfvPPA. C9orf72 positive ALS-FTD patients exhibited both anterior and posterior lobe cerebellar volume loss, while bvFTD and nfvPPA patients showed posterior cerebellar atrophy. Flocculonodular degeneration was observed in nfvPPA and cerebellar crura atrophy in bvFTD. Bilateral corticospinal tract and corpus callosum degeneration was detected in ALS-FTD, bvFTD, and nfvPPA. Primary motor cortex volume reductions were captured in both ALS-FTD and nfvPPA.</p><p><strong>Conclusions: </strong>Our analyses capture significant cerebro-cerebellar disconnection in frontotemporal dementia. Corticospinal tract and motor cortex degeneration can be readily detected in non-ALS phenotypes. Intra-cerebellar pathology, coupled with the degeneration of cerebellar projections and the ensuing dysfunction of cerebro-cerebellar networks likely contribute to phenotype-defining clinical profiles in frontotemporal dementia. Infratentorial disease burden and cerebellar network dysfunction should, therefore, be carefully considered in FTD, and phenotype-defining neuropsychological profiles should not be solely attributed to supratentorial degeneration.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"289"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710092","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":"Global trends and projections of Parkinson's disease incidence: a 30-year analysis using GBD 2021 data.","authors":"Libo Xu, Zhenhao Wang, Qingsong Li","doi":"10.1007/s00415-025-13030-2","DOIUrl":"https://doi.org/10.1007/s00415-025-13030-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Parkinson's disease (PD) is a neurodegenerative disorder marked by the progressive loss of dopaminergic neurons, leading to motor dysfunction and non-motor symptoms like cognitive decline and depression. With the aging global population, PD incidence is anticipated to rise, especially in regions with rapidly growing elderly populations. This study leverages Global Burden of Disease (GBD) 2021 data to analyze the burden of PD by region, sex, and age group, examining trends from 1992 to 2021 and projecting the future burden to 2030.</p><p><strong>Methods: </strong>Data from the GBD 2021 database for the years 1992-2021 were analyzed to assess age-standardized incidence rates (ASIR) and mortality of PD across socio-demographic index (SDI) regions, sex, and age groups. The Age-Period-Cohort (APC) model was used to explore temporal trends, while the Bayesian Age-Period-Cohort (BAPC) model projected future PD burden from 2022 to 2030.</p><p><strong>Results: </strong>From 1992 to 2021, global PD cases increased from 450,000 to 1.34 million, with crude incidence rates rising from 8.19 to 16.92 per 100,000 and ASIR from 11.54 to 15.63 per 100,000, indicating an annual net drift of 1.11% (95% CI 1.06%-1.17%), reflecting a growing burden driven by an aging population. All SDI regions saw a growth in PD burden, with the highest increases in middle- and high-middle-SDI regions, where male incidence was notably higher than female. Incidence rates escalated sharply in individuals aged 60 and older, peaking in those aged 85 and above. Projections suggest that by 2030, global PD cases will reach 1.93 million, with an ASIR of 27 per 100,000.</p><p><strong>Discussion: </strong>The findings highlight a sustained global increase in PD burden, particularly in middle- and high-income regions and among men. In low-SDI areas, PD burden may be underestimated due to limited healthcare access and diagnostic challenges. These results stress the urgent need for health policies focused on elderly populations, especially men, and call for effective prevention and intervention strategies to mitigate the future impact of PD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"286"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710103","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}