Journal of Neurology最新文献

{"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}

{"title":"Intravenous immunoglobulin as first-line acute treatment in adults with autoimmune encephalitis caused by antibodies to NMDAR, LGI1 and CASPR2.","authors":"Joyce Christin Rittel, Dominica Hudasch, Kathrin Doppler, Florian Then Bergh, Martin Lesser, Orhan Aktas, Michael Nagel, Hagen B Huttner, Kevin Rostasy, Simone Tauber, Manuel A Friese, Michael Malter, Marie Madlener, Andrea Kraft, Frank Hoffmann, Jan Lewerenz, Makbule Senel, Jonathan Wickel, Christian Geis, Andreas Moser, Klaus-Peter Wandinger, Thorsten Bartsch, Frank Leypoldt, Franziska Thaler, Tania Kümpfel, Sven Meuth, Nico Melzer, Carsten Finke, Harald Prüss, Martin Stangel, Kurt-Wolfram Sühs","doi":"10.1007/s00415-025-13032-0","DOIUrl":"10.1007/s00415-025-13032-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>Corticosteroids or plasma exchange are recommended for acute treatment of autoimmune encephalitis (AE). Intravenous immunoglobulins (IVIG) are suggested as an additional treatment option but data on treatment effect is scarce. The objective of the present study was to investigate the impact of the first-line treatment on the three most common forms of AE, in particular, to evaluate the effect of IVIG therapy in these diseases.</p><p><strong>Methods: </strong>A total of 1274 patients from the German Network for Autoimmune Encephalitis Research (GENERATE) were analyzed, and 388 patients were included in the study because they had either anti-NMDAR, anti-LGI1 or anti-CASPR2 antibodies and firs-line immunotherapy (ivMP monotherapy, ivMP + IVIG, ivMP + PE or ivMP + IVIG + PE) or no immunotherapy at all. For the statistical analyses, patients were stratified according to antibody type, distinguishing between anti-NMDAR (IgG1) and anti-LGI1 as well as anti-CASPR2 (predominantly IgG4). The primary endpoint was the clinical outcome at discharge, which was assessed using the modified Rankin Scale (mRS). The mRS scores were then compared between the different treatment groups over time, and the factors influencing the reduction in mRS at discharge were analyzed. Furthermore, a specific investigation was conducted to determine the differences in outcomes between patients treated with ivMP + IVIG and ivMP + PE, each split by antibody subtype.</p><p><strong>Results: </strong>In all treatment groups analyzed, significant improvements were observed at the time of discharge and after 12 months compared to disease onset, regardless of the type of first-line treatment. In untreated patients a significant improvement was not observed. The choice of IVIG or PE as an additional treatment to ivMP for anti-NMDAR encephalitis did not affect the primary outcome. In anti-LGI1 or anti-CASPR2 encephalitis, no influence on the primary outcome was observed when IVIG or PE was administered in addition to ivMP, too. However, a direct comparison of the individual antibody subgroups' mRS reductions, depending on the treatment approach (ivMP + IVIG vs. ivMP + PE), revealed that a more significant mRS reduction was observed with ivMP + PE in anti-NMDAR encephalitis.</p><p><strong>Discussion: </strong>The retrospective data give evidence that there is no difference in outcome for the use of ivMP + PE over ivMP + IVIG or vice versa in the treatment of encephalitis caused by antibodies against NMDAR, LGI1 or CASPR2. Furthermore, the specific method of plasma exchange, whether plasmapheresis or immunoadsorption, did not affect the mRS at discharge.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"287"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710104","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":"Vestibular dysfunction: a hidden risk factor for Alzheimer's disease.","authors":"Carolin Anna Maria Koriath, Boris Rauchmann, Florian Schoeberl, Andreas Zwergal, Peter Falkai, Robert Perneczky","doi":"10.1007/s00415-025-13045-9","DOIUrl":"10.1007/s00415-025-13045-9","url":null,"abstract":"<p><strong>Background: </strong>London taxi drivers' navigationally challenged hippocampi are known to be enlarged, and reduced Alzheimer's disease (AD)-related mortality has recently been shown in similarly well-versed drivers, implying a neuroprotective effect through hippocampal engagement. Vestibular function has been linked to hippocampal size, suggesting that vestibular input may influence AD risk.</p><p><strong>Methods: </strong>Including 16 known modifiable lifestyle factors as covariates, we analyzed UK Biobank (UKB) volunteers aged over 55 years and without dementia at baseline to assess how peripheral vestibular dysfunction (PVD) influences the likelihood of an AD diagnosis.</p><p><strong>Results: </strong>4684 AD and 2133 PVD cases were identified based on their ICD diagnoses; even accounting for other risk factors, PVD increased the risk of AD 1.7 times in UKB volunteers.</p><p><strong>Discussion: </strong>Vestibular loss, linked to hippocampal atrophy and default mode network disruption, appears to increase AD risk. Consequently, active vestibular stimulation by balance training or neuromodulation could offer potential for modifying AD progression.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"285"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710109","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 autoantigens in autoimmune limbic encephalitis using phage immunoprecipitation sequencing.","authors":"Haidara Kherbek, Naveen K Paramasivan, Surendra Dasari, Carley Karsten, Smathorn Thakolwiboon, Michael Gilligan, Andrew M Knight, Reghann G LaFrance-Corey, Vaniolky Losada, Andrew McKeon, Sean J Pittock, Anastasia Zekeridou, John R Mills, Divyanshu Dubey","doi":"10.1007/s00415-025-13039-7","DOIUrl":"https://doi.org/10.1007/s00415-025-13039-7","url":null,"abstract":"<p><strong>Objectives: </strong>To describe the use of high-throughput whole-human proteome phage immunoprecipitation sequencing (PhIP-Seq) in identifying potential antigens for antibody-negative autoimmune limbic encephalitis (ALE).</p><p><strong>Methods: </strong>We used PhIP-Seq to analyze cerebrospinal fluid (CSF) from patients with antibody-negative ALE evaluated in our lab with detailed clinical records available (2008-2023). Identified autoantigens were validated using recombinant protein-based assay.</p><p><strong>Results: </strong>Of the 18 CSF samples from patients with ALE, 1 sample showed neuronal PAS domain protein 4 (NPAS4) as the putative autoantigen with the highest enrichment score. Patient presented with cognitive decline, gait dysfunction and unique MRI brain findings revealing asymmetric involvement of the medial temporal lobes with extension to the insular cortex and anterior temporal lobes. No malignancy was detected, and although the patient was initiated on immunotherapy, follow-up evaluation was limited. Another sample with very similar clinical and MRI brain findings, who developed ALE following COVID-19 infection, was referred for evaluation for neural-specific autoantibodies, and PhIP-Seq identified NPAS4 as the putative autoantigen. In both these samples, NPAS4-IgG was confirmed by cell-based assay (CBA) and enzyme-linked immunosorbent assay (ELISA). To assess the specificity of the NPAS4 autoantigen, a large cohort of disease (CSF, n = 49, serum, n = 220) and healthy controls (serum, n = 90) were tested by ELISA which were also negative. In addition, three samples had a high enrichment score for adenylate kinase 5 (AK5), an autoantigen associated with ALE. These patients also displayed a unique immunosignature that included AK5-IgG, which is distinct from NPAS4-IgG ALE or antibody-negative ALE. All three AK5-IgG seropositive cases presented with subacute memory loss, with MRI/PET brain florid showing medial temporal lobe involvement. No malignancy was detected in any of the three patients and immunotherapy led to improvement in one.</p><p><strong>Conclusion: </strong>Our study demonstrates the utility of high-throughput PhIP-Seq in identifying potential autoantigens in antibody-negative ALE. The identification of NPAS4 as a putative antigen and identification of additional AK5-IgG-positive cases, underscores the potential of PhIP-Seq as a powerful tool in autoimmune disease research.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 4","pages":"292"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710102","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}