Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"CGG repeat expansions in Charcot-Marie-Tooth disease: insights from the 100 000 Genomes Project.","authors":"Alessandro Bertini, Stefano Facchini, Ilaria Quartesan, Riccardo Currò, Ricardo Parolin Schnekenberg, Natalia Dominik, Gustavo Alves, Lucia Ferullo, Arianna Tucci, Henry Houlden, Mary M Reilly, Andrea Cortese","doi":"10.1136/jnnp-2025-336590","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336590","url":null,"abstract":"<p><strong>Background: </strong>CGG expansions in <i>NOTCH2NLC</i> and <i>LRP12</i> were recently identified as a cause of Charcot-Marie-Tooth disease (CMT) in 1.2%-10.6% of genetically undiagnosed patients in China, Taiwan and Japan. However, their relevance in CMT patients of different ethnic origin is still unknown.</p><p><strong>Methods: </strong>Here, we leveraged short-read whole genome sequencing data from the 100 000 Genomes Project to investigate the presence and frequency of CGG expansions in <i>NOTCH2NLC</i>, <i>LRP12</i> and additional genes associated with oculopharyngodistal myopathy (OPDM), in 560 genetically unsolved patients diagnosed with CMT and 32 509 non-neurological controls.</p><p><strong>Results: </strong>Repeat expansions in <i>NOTCH2NLC</i>, <i>LRP12</i>, <i>RILPL1</i>, <i>NUTM2B-AS1</i> and <i>ABCD3</i> were absent from 560 genetically unsolved patients with CMT, mostly of Northern European ancestry. One patient of African ancestry carried an expanded allele in <i>GIPC1</i>, below the reported pathogenic threshold. However, rare expansions in this gene, as well as in <i>NOTCH2NLC</i>, <i>NUTM2B-AS1</i> and <i>ABCD3</i>, were also detected in controls (≤0.05%). The distribution of repeat size at these loci varied significantly across different ethnicities, with larger non-pathogenic intermediate alleles of <i>NOTCH2NLC</i> and <i>LRP12</i> typically observed in East Asians.</p><p><strong>Conclusions: </strong>CGG expansions in <i>NOTCH2NLC</i>, <i>LRP12</i> and other OPDM-associated genes do not appear to be a relevant cause of CMT in the UK. The larger size of non-pathogenic intermediate alleles of <i>NOTCH2NLC</i> and <i>LRP12</i> in East Asians could explain their ancestry-specific propensity to further expand into the full pathogenic range.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KFLC-index distinguishes multiple sclerosis from anti-myelin oligodendrocyte glycoprotein and aquaporin 4 diseases in a Chinese cohort.","authors":"Hongmei Tan, Xuan Deng, Jingzi ZhangBao, Lei Zhou, Wenqing Wu, Haiqing Li, Yuxin Li, Yuxin Fan, Zhouzhou Wang, Yiqin Xiao, Chongbo Zhao, Ming Guan, Chao Quan, Haoqin Jiang","doi":"10.1136/jnnp-2025-335953","DOIUrl":"https://doi.org/10.1136/jnnp-2025-335953","url":null,"abstract":"<p><strong>Background: </strong>Kappa free light chain (KFLC) index has emerged as a diagnostic biomarker for multiple sclerosis (MS). This study aims to evaluate the diagnostic accuracy of the KFLC-index in Chinese patients with MS, and its capacity to discriminate MS from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorders with aquaporin-4 antibody (AQP4+NMOSD).</p><p><strong>Methods: </strong>428 patients tested for KFLC-index were enrolled in the study, including 130 patients with MS, 41 with MOGAD, 25 with AQP4+NMOSD, 123 with other inflammatory or infectious neurological disorders (OIND) and 109 with non-inflammatory neurological disorders (NIND). Their oligoclonal band (OCB) results and clinical data were reviewed.</p><p><strong>Results: </strong>KFLC-index was significantly higher in MS (20.1 (0.9-388.9)) compared with MOGAD (4.8 (0.8-56.1), p=0.003), AQP4+NMOSD (4.5 (1.5-46.4), p=0.011), OIND (2.9 (0.6-238.7), p<0.001) and NIND (1.8 (0.6-110.7), p<0.001). The optimal cut-off value for the KFLC-index to identify MS from the non-selective controls was 8.3, with an accuracy comparable to that of OCB (area under the curve 0.84 vs 0.81, p=0.249). The optimal cut-off values for differentiating MS from MOGAD and AQP4+NMOSD were 18.5 and 12.1, with performance similar to OCB (p=0.756 and 0.064). Combination of KFLC-index and OCB outperformed OCB alone in differentiating MS from non-selective controls and MOGAD (p<0.001 and p=0.044). Female (p=0.009) and higher cerebrospinal fluid leucocyte count (p<0.001) were associated with higher KFLC-index in MS.</p><p><strong>Conclusion: </strong>KFLC-index is a valuable diagnostic tool for differentiating MS from other inflammatory demyelinating diseases.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic biology linking traumatic brain injury to multiple sclerosis susceptibility.","authors":"David Baker, Lars Alfredsson, Anna Karin Hedström, Klaus Schmierer","doi":"10.1136/jnnp-2024-335304","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335304","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a major, immune-mediated, demyelinating disease and the major cause of non-traumatic disability in young adults. Susceptibility to disease is controlled by a variety of interacting features that include genetic and notably environmental factors. One of these risk factors appears to be the occurrence of traumatic brain injury. In a follow-on to previous analysis of head injury-induced risk factors for MS, analysis of Swedish Registry data of MS and matched controls demonstrates enhanced susceptibility to MS, notably when stratified for the presence of HLA-DRB1*15.01, absence of HLA-A*02.01 and occurrence of smoking, which are known risk factors, the risk of MS increases to OR 65.4 (95% CI 8.35 to 512). This can be mechanistically supported by a number of routes whereby brain injury can lead to expression of autoantigenic targets, or damage-related release of neuroantigens that could generate a novel autoantigenic response in draining lymph nodes following glymphatic/meningeal lymphatic drainage. These may be different from other mechanisms that are relevant to susceptibility due to human leucocyte antigen expression and smoking.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum level changes of the synaptic marker beta-synuclein in Alzheimer's disease continuum and other dementias.","authors":"Lorenzo Barba, Giovanni Bellomo, Daniel Alcolea, Anna L Wojdala, Lorenzo Gaetani, Juan Fortea, Samir Abu-Rumeileh, Alberto Lleó, Lucilla Parnetti, Olivia Belbin, Markus Otto, Patrick Oeckl","doi":"10.1136/jnnp-2025-336189","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336189","url":null,"abstract":"<p><strong>Background: </strong>Beta-synuclein is an emerging blood biomarker for detecting synaptic damage in Alzheimer's disease (AD) but its role in early AD as well as in other dementias is unclear.</p><p><strong>Methods: </strong>We measured with immunoprecipitation mass-spectrometry serum beta-synuclein levels in an exploratory cohort of 80 patients recruited at the University of Perugia (Perugia, Italy) (n=56 AD; n=24 controls) and in a validation cohort of 269 patients recruited at the University of Barcelona (Barcelona, Spain) (n=108 AD; n=53 frontotemporal lobar degeneration (FTLD); n=73 dementia with Lewy bodies and mild cognitive impairment (MCI) with Lewy bodies, together Lewy body disease (LBD); n=27 controls). We tested associations with diagnostic groups, cognitive decline and other cerebrospinal fluid (CSF) and blood markers (phosphorylated tau protein in position 181 (pTau181), neurofilament light chain protein (NfL), glial fibrillar acidic protein (GFAP)).</p><p><strong>Results: </strong>Serum beta-synuclein level was progressively increased in the AD continuum across the preclinical, MCI and dementia stages compared with controls and was correlated with serum pTau181 (r=0.710), NfL (r=0.494) and GFAP concentrations (r=0.621, p<0.001 for all). The biomarker showed high accuracy for the discrimination of AD vs controls (area under the curve (AUC): 0.87) and AD-MCI vs non-AD MCI (AUC: 0.96). High serum beta-synuclein level was correlated with lower Mini-Mental State Examination (MMSE) points at baseline (r=-0.461, p<0.001) and associated with MMSE change at follow-up after accounting for age, sex and the time from baseline to last follow-up visit (p=0.006). Serum beta-synuclein level was similar between FTLD and controls, whereas, in LBD, it was higher with AD copathology as evidenced by CSF analysis (p<0.001).</p><p><strong>Conclusion: </strong>High serum beta-synuclein level is a promising biomarker for AD-related synaptic damage.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subthalamic deep brain stimulation in isolated generalised or segmental dystonia (RELAX Study): a multicentre, randomised, double-blind, controlled trial.","authors":"Lin Wang, Huifang Shang, Lingjing Jin, Nian Xiong, Xingyue Hu, Wei Wang, Yiming Liu, Jun Yan, Lingling Gao, Yaning Wang, Yanying Wang, Peng Fu, Huaying Cai, Wenbin Zhang, Shujun Xu, Fei Teng, Ruwei Ou, Lei Qiao, Yingmai Yang, Mengyu Zhang, Yi Guo, Xinhua Wan","doi":"10.1136/jnnp-2025-335829","DOIUrl":"10.1136/jnnp-2025-335829","url":null,"abstract":"<p><strong>Background: </strong>The safety and effectiveness of deep brain stimulation of the subthalamic nucleus (STN-DBS) for the treatment of dystonia lack high-level evidence-based medical support. This study aimed to clarify the efficacy and safety of STN-DBS and perform a post hoc analysis comparing it with DBS of the internal globus pallidus (GPi-DBS).</p><p><strong>Methods: </strong>This multicentre, randomised, double-blind, controlled trial included 67 patients aged 6-60 years old diagnosed with genetic or idiopathic isolated generalised or segmental dystonia. They were enrolled from seven hospitals in China and randomly assigned to undergo GPi-DBS or STN-DBS. After surgery, they were randomised to receive either neurostimulation or sham stimulation for 3 months. At the 3-month follow-up, neurostimulation was also initiated in the sham stimulation group, and all patients were followed up for more than 3 years after treatment. The primary outcome was the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) score.</p><p><strong>Results: </strong>In the STN group, the neurostimulation subgroup exhibited significant improvement (p<0.001), which is also superior to the sham stimulation subgroup (p=0.028) at 3-month follow-up. At the 6-month and >3-year follow-ups, all patients receiving STN-DBS showed a significant improvement in BFMDRS-M scores (p<0.001). Further post hoc analysis revealed that both STN-DBS and GPi-DBS could produce similar therapeutic effects on motor symptoms (P_{6 months}=0.865, P_{>3 years}=0.905). There were no ongoing serious adverse events throughout the study.</p><p><strong>Conclusions: </strong>For isolated generalised and segmental dystonia patients, the STN is a selectable DBS target with ensured safety and efficacy. STN-DBS and GPi-DBS may achieve comparable therapeutic effects on motor symptoms.</p><p><strong>Trial registration number: </strong>NCT03017586.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using prodromal non-motor symptoms to predict Parkinson's disease onset and motor phenotype.","authors":"Joshua Pearson, James B Badenoch, Daniel Van Wamelen","doi":"10.1136/jnnp-2024-335429","DOIUrl":"10.1136/jnnp-2024-335429","url":null,"abstract":"<p><strong>Background: </strong>Non-motor symptoms are highly prevalent in prodromal Parkinson's disease (PD); however, their impact on PD trajectory remains largely unexplored. We aimed to assess whether prevalent prodromal non-motor symptoms could predict future motor phenotype and time-to-PD diagnosis.</p><p><strong>Methods: </strong>We studied the prodromal cohort of the ongoing Parkinson's Progression Markers Initiative (n=958), which prospectively assesses individuals with prodromal PD features (genetic: n=361, hyposmia: n=298, rapid eye movement behaviour disorder: n=136, combination: n=163) with up to 10 years of follow-up. The presence of prevalent prodromal symptoms was defined by evidence-based cut-off scores. In unmedicated or OFF-state PD converters (total n=52), binary logistic regression models established whether these predicted non-tremor-dominant (n=35) and tremor-dominant (n=17) motor phenotypes at diagnosis. Cox proportional hazards models determined whether identified prodromal symptoms predicted a shorter time-to-phenoconversion across all PD converters (n=59) and non-converters (n=343). Both models adjusted for age and sex.</p><p><strong>Results: </strong>Prodromal anxiety and hyposmia were each associated with an increased risk of subsequent non-tremor-dominant PD, compared with other motor phenotypes (adjusted OR=4.45, 95% CI 1.34 to 15.27 and adjusted OR=3.90, 95% CI 1.01 to 15.16, respectively). Concurrent prodromal anxiety and hyposmia predicted an increased risk of PD phenoconversion over time (HR=4.93, 95% CI 2.71 to 8.98).</p><p><strong>Conclusion: </strong>In this exploratory analysis, individuals with prodromal hyposmia and anxiety phenoconverted to PD sooner and more often had a non-tremor-dominant phenotype, potentially reflecting more widespread pathology or specific pathophysiology underlying these symptoms. This may improve phenotyping prodromal PD and stratifying poorer prognostic trajectories for earlier and more personalised management.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF levels of the somatodendritic protein MAP2 are increased in ALS and predict shorter survival.","authors":"Federico Verde, Jakub Vávra, J Dorst, Zeynep Elmas, Maximilian Wiesenfarth, Anna De Gobbi, Antonia Ratti, Barbara Poletti, Hayrettin Tumani, Jochen Weishaupt, Vincenzo Silani, Nicola Ticozzi, Markus Otto, Albert C Ludolph, Patrick Oeckl","doi":"10.1136/jnnp-2025-336208","DOIUrl":"10.1136/jnnp-2025-336208","url":null,"abstract":"<p><strong>Background: </strong>Previous proteomic work has identified the somatodendritic protein MAP2 as a new candidate cerebrospinal fluid (CSF) biomarker for amyotrophic lateral sclerosis (ALS).</p><p><strong>Methods: </strong>We measured CSF levels of MAP2 and neurofilament light chain (NFL) in a retrospective cohort of 251 patients with ALS and 108 neurological controls (NCs).</p><p><strong>Results: </strong>Patients with ALS had a higher median CSF MAP2 level compared with NCs, leading to an area under the curve (AUC) of 0.7080 (p<0.0001). They also had a higher median CSF NFL level (p<0.0001), resulting in an excellent diagnostic performance (AUC=0.9641; p<0.0001). Among patients with ALS, CSF MAP2 correlated with disease progression rate (DPR) (r=0.3099; p<0.0001) and was negatively associated with survival (HR=3.174). CSF NFL also correlated with DPR (r=0.4936; p<0.0001) and was negatively associated with survival (HR=2.759). The association of MAP2 with DPR was independent from NFL (p=0.0037). Stratifying patients based on median levels of both biomarkers resulted in significant differences in median survival times (low NFL/low MAP2, 66 months; high NFL/low MAP2 and vice versa, 35 months; high NFL/high MAP2, 26 months; p<0.0001). MAP2 was also associated with genetic status in patients with ALS, as patients with no mutations in <i>C9ORF72</i> or in <i>SOD1</i>, as well as <i>C9ORF72</i>-positive ones, had higher median levels compared with NCs (p<0.0001), while patients with <i>SOD1</i> mutations did not significantly differ from NCs (p>0.9999).</p><p><strong>Conclusions: </strong>Our study shows that the somatodendritic protein MAP2 is a promising candidate CSF biomarker for ALS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QSM predicts haemorrhage risk in brainstem cavernous malformations: a multicentre prospective study.","authors":"Si-Hui Wang, Hong-Wei Li, Jian-Cong Weng, Yan-Bing Yu, Gui-Jun Zhang, Bo-Han Yao, Pan-Pan Liu, Lu Kong, Hui Zhou, Hao-Yu Zhang, Xiao-Jun Zeng, Ze-Yu Wu, Cong Ren, Wei Wang, Hong-Jun Zhang, Jun-Peng Ma, Xiao-Ying Xu, Lai-Rong Song, Jun-Ting Zhang, Zhen Wu, Liang Wang, Sheng-Jun Sun, Da Li","doi":"10.1136/jnnp-2025-336149","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336149","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the predictive value of baseline quantitative susceptibility mapping (QSM) metrics for assessing the risk of future symptomatic haemorrhages in patients with brainstem cavernous malformations (CMs).</p><p><strong>Methods: </strong>From July 2020 to September 2023, a prospective multicentre cohort of 155 patients with brainstem CMs was enrolled from 12 institutions. We analysed baseline QSM metrics, including lesional mean, median, IQR and maximum susceptibility. Propensity score matching was adjusted for baseline confounders, and Cox regression models assessed haemorrhage risk. Risk stratification was performed based on thresholds determined from planned receiver operating characteristic (ROC) analyses.</p><p><strong>Results: </strong>Postmatching cohorts (56 haemorrhage-free vs 30 haemorrhage cases) showed balanced baseline characteristics. Over a mean follow-up of 22.6 months, the baseline QSM metrics, particularly the median susceptibility (QSMmedian) (HR 58.896, 95% CI 8.544 to 405.989, p<0.001; Bonferroni-adjusted p=0.0001, k=4) and IQR of susceptibility (QSMIQR) (HR 29.754, 95% CI 6.101 to 145.119, p<0.001; Bonferroni-adjusted p=0.0001, k=4) were associated with prospective haemorrhage after adjusting for age, gender, lesion volume and prior haemorrhage. QSMmedian (area under curve (AUC)=0.759) and QSMIQR (AUC=0.740) demonstrated modest predictive performance. Risk stratification based on QSMmedian and QSMIQR demonstrated 2-year haemorrhage-free survival rates of 83.3%, 62.8% and 35.7% for the low-risk, intermediate-risk and high-risk groups, respectively. High-risk patients showed a 7.7-fold greater risk of haemorrhage compared with the low-risk group.</p><p><strong>Conclusions: </strong>This study explored the predictive value of QSM metrics for future symptomatic haemorrhage, suggesting that QSM may serve as a complementary imaging biomarker to existing prognostic models. Further validation in larger, independent cohorts is warranted.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum neuronal pentraxin 2 levels are associated with shorter survival in amyotrophic lateral sclerosis.","authors":"Soha Alali, Jonas Dubin, Frederik Hobin, Shreyasee Das, Charlotte Lambrechts, Erik Stoops, Eugen Vanmechelen, Philip van Damme, Koen Poesen","doi":"10.1136/jnnp-2025-336198","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336198","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple sclerosis from onset to secondary progression: a 30-year Italian register study.","authors":"Aurora Zanghì, Massimiliano Copetti, Carlo Avolio, Damiano Paolicelli, Marzia Anita Lucia Romeo, Francesco Patti, Giovanna De Luca, Maria Pia Amato, Simonetta Galgani, Patrizia Sola, Giuseppe Salemi, Paolo Gallo, Franco Granella, Silvia Romano, Mauro Zaffaroni, Roberto Bergamaschi, Carlo Pozzilli, Giacomo Lus, Marika Vianello, Maria Trojano, Emanuele D'Amico","doi":"10.1136/jnnp-2025-335958","DOIUrl":"https://doi.org/10.1136/jnnp-2025-335958","url":null,"abstract":"<p><strong>Background: </strong>Three decades have passed since the initial approval of disease-modifying therapies (DMTs). Ongoing discussion is focused on fundamental aspects of the disease, highlighting a growing division between successes in managing relapsing multiple sclerosis (MS) and the persistent challenges posed by disease progression.</p><p><strong>Methods: </strong>A cohort study on prospectively acquired data from the Italian MS register. The primary outcome was to describe the MS disease course from onset to secondary progression (SP) defined according to a data-driven algorithm over 30 years follow-up and according to five different eras of disease onset.</p><p><strong>Results: </strong>A total cohort of 9958 patients was analysed; 1364 converted to SP after a mean of 8.5 (SD 5.5) years. A higher rate of patients converting to SP had never been exposed to DMTs (135, 9.9% vs 424, 5.2%) than non-converting ones. The treatment coverage was also lower in patients converting to SP than non-converting ones 58.4 (SD 31.5) vs 73.6 (SD 27.6).The SP incidence rate was 1.26 (95% CI 1.19 to 1.32) overall. The rates showed a downward trend among the different eras: from 1st era 1.98 (95% CI 1.73 to 2.27) to 5th era 1.15 (95% CI 0.97 to 1.35).In the multivariable Cox model, 10% increase of treatment coverage was associated to 19% lower risk to convert to SP (10%, HR 0.89, 95% CI 0.87 to 0.90).</p><p><strong>Conclusions: </strong>This 30-year analysis suggests that SP conversion rates have decreased over time, partially explained by improvements in therapeutic coverage. Future research should adopt a multifaceted approach to develop more comprehensive models of disease progression.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}