Journal of Neurology最新文献

{"title":"KCNT1 gene variant-associated epilepsy: genetic insights, functional mechanisms, and emerging therapies.","authors":"Ya-Ze Duan, Tong-Tong Yao, Yi-Ting Shao, Li-Ming Liu, Hui Zhou, Yong Cheng","doi":"10.1007/s00415-025-13207-9","DOIUrl":"https://doi.org/10.1007/s00415-025-13207-9","url":null,"abstract":"<p><p>KCNT1 gene variant-associated epilepsy is a rare genetic disorder with a wide clinical spectrum, ranging from mild symptoms to severe, early onset epileptic encephalopathies. It is commonly characterized by focal seizures, drug resistance, and neurodevelopmental impairments. This review summarizes recent advances in understanding the disorder's molecular mechanisms, clinical features, experimental models, and emerging therapeutic approaches. KCNT1 mutations disrupt potassium channel function, altering neuronal excitability and impairing network stability. Experimental models-including mice, Drosophila, and patient-derived cells-have provided critical insights into disease mechanisms and potential interventions. In particular, KCNT1 knock-in mouse and cellular models have clarified how specific variants drive disease progression and therapeutic response. Promising strategies under investigation include gene therapy, small-molecule modulators, and ketogenic dietary (KD) interventions, all aimed at restoring neuronal balance. These developments highlight the central role of potassium channel dysfunction in the pathophysiology of KCNT1-related epilepsy. Nevertheless, current models do not fully recapitulate the human condition, underscoring the need for continued research. This review aims to support ongoing efforts to refine precision therapies and improve outcomes for patients affected by this complex disorder.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"472"},"PeriodicalIF":4.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340213","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":"Prevalence, timing and characteristics of delirium preceding dementia with Lewy bodies: a retrospective case series.","authors":"Janice Taylor, Chaminda Gunawardana, Simon J G Lewis, Elie Matar","doi":"10.1007/s00415-025-13193-y","DOIUrl":"10.1007/s00415-025-13193-y","url":null,"abstract":"<p><strong>Background: </strong>Consensus diagnostic criteria for delirium-onset dementia with Lewy bodies are lacking. This retrospective study aimed to identify delirium occurring in the prodrome of dementia with Lewy bodies (DLB), exploring delirium-onset DLB as an entity and its natural history.</p><p><strong>Methods: </strong>Thirty-four participants with an established diagnosis of probable DLB from an outpatient neurology clinic in Sydney underwent a structured telephone interview to identify episodes of delirium. The timing, precipitants, and phenomenology of each episode were documented. Core and supportive features from the proposed diagnostic criteria for DLB were evaluated.</p><p><strong>Results: </strong>26% of the participants experienced delirium prior to diagnosis of DLB, with one participant experiencing multiple episodes in the 24 months before diagnosis. Of these cases, 66% demonstrated some core and supportive features of DLB at the time of their delirium. In addition to expected triggers (e.g. surgery), international (long-haul) air flight was identified as one of the commonest precipitants for delirium in this group. Those DLB cases who fulfilled the proposed research criteria for a delirium-onset prodrome experienced a shorter time from symptom onset to dementia than those DLB patients with no history of pre-diagnosis delirium (26 vs 40 months).</p><p><strong>Conclusions: </strong>These findings support delirium as a marker of prodromal DLB and suggest delirium-onset cases exhibit a more rapid progression to dementia, offering a focus for future studies. Identifying delirium as a potential early feature of DLB could aid in earlier recognition and improve diagnostic accuracy, particularly in individuals presenting with precipitants such as international air travel.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"471"},"PeriodicalIF":4.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340214","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":"Alix Joffroy (1844-1908).","authors":"Hélio Afonso Ghizoni Teive, Léo Coutinho, Francisco M Branco Germiniani, Carlos Henrique Ferreira Camargo, Olivier Walusinski","doi":"10.1007/s00415-025-13198-7","DOIUrl":"https://doi.org/10.1007/s00415-025-13198-7","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"470"},"PeriodicalIF":4.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333325","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":"Influence of triptans use on anti-CGRP mAbs response: a prospective, cohort study.","authors":"Catello Vollono, Marina Romozzi, Antonio Munafò, Giulia Vigani, Francesco De Cesaris, Paolo Calabresi, Luigi Francesco Iannone","doi":"10.1007/s00415-025-13202-0","DOIUrl":"https://doi.org/10.1007/s00415-025-13202-0","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to compare the differences in clinical characteristics and response to monoclonal antibodies against CGRP (anti-CGRP mAbs) between patients who habitually used triptans (TRIPTANS group) and patients who were non-current users (NO-TRIPTANS group).</p><p><strong>Methods: </strong>In this prospective cohort study, all consecutive outpatients treated with anti-CGRP mAbs for 12 months were included. Clinical data were collected at baseline and monthly: number of headache days (MHDs), the absolute number of analgesics (AMNs), and the number of days with at least one analgesic (AMDs), Headache Impact Test-6 (HIT-6), and Migraine Disability Assessment (MIDAS) questionnaires. The outcomes were to evaluate the differences between TRIPTANS and NO-TRIPTANS groups (users or non-users of triptans in the 6 months before and during anti-CGRP mAb treatment) in MHDs and the other clinical variables during treatment. Response rates were assessed based on reductions in MHDs (≤ 25%, ≥ 50%, ≥ 75%).</p><p><strong>Results: </strong>A total of 336 patients treated with mAbs were included. At baseline, NO-TRIPTANS group had higher MHDs (24.7 ± 6.7) compared to the TRIPTANS group (21.8 ± 6.9), p < 0.001. Comparative and normalized analyses showed significant and sustained lower MHDs in the TRIPTANS group during treatment. The MIDAS score was also significantly lower in the TRIPTANS group at month-3, 6, 9, 12, and lower AMDs and AMNs compared to NO-TRIPTANS group were seen in most of the time-points. The number of patients with ≥ 50% reduction of MHDs was significantly higher in the TRIPTANS group at months 1 and 12.</p><p><strong>Conclusions: </strong>This study showed greater effectiveness of anti-CGRP mAb in habitual triptans users, possibly due to a common and/or synergistic action.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"468"},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326080","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":"Exploring NEK1 genetic variability in Italian amyotrophic lateral sclerosis patients.","authors":"Viviana Pensato, Silvia Peverelli, Cinzia Tiloca, Stefania Magri, Alberto Brusati, Monica Pingue, Claudia Morelli, Eleonora Dalla Bella, Arianna Manini, Pierpaola Tannorella, Alberto Doretti, Jessica Mandrioli, Fabrizia Terenghi, Alessandro Prelle, Nilo Riva, Federico Verde, Roberto Eleopra, Franco Taroni, Giuseppe Lauria Pinter, Vincenzo Silani, Nicola Ticozzi, Cinzia Gellera, Antonia Ratti","doi":"10.1007/s00415-025-13153-6","DOIUrl":"10.1007/s00415-025-13153-6","url":null,"abstract":"<p><strong>Background: </strong>Mutations in NEK1, encoding for a serine/threonine kinase which regulates several biological processes, are associated with amyotrophic lateral sclerosis (ALS).</p><p><strong>Methods: </strong>NEK1 was analysed by amplicon deep sequencing in a cohort of 1016 Italian sporadic and familial ALS patients previously screened for C9orf72, SOD1, TARDBP and FUS mutations.</p><p><strong>Results: </strong>We identified 28 rare NEK1 variants in 29 patients (2.85%) of whom 20/782 were sporadic (2.5%), 6/107 familial (5%) and 3/127 of unknown aetiology (2.3%). Variants were classified as pathogenic (P; n = 1), likely pathogenic (LP; n = 6 in 7 patients) and of unknown significance (VUS; n = 21) according the American College of Medical Genetics and Genomics criteria. Notably, 64% of the identified variants (18/28, including 4 LP and 14 VUS) were novel. Among the 29 patients with rare NEK1 variants, 7 (of whom 5 were familial cases) had additional variants in one of the four main ALS causative genes. Moreover, 23 patients carried the already reported NEK1 p.Arg261His risk variant (VUS) alone or in addition to SOD1 mutations (n = 1) or C9orf72 repeat expansion (n = 2) and to the NEK1 p.Asp128Val variant (n = 1). Genotype-phenotype correlation analysis showed no significant differences in age at onset or survival in NEK1 variant carriers, independently on the variant type. No flail arm phenotype, but atypical features, including sensory symptoms, were present in NEK1 carriers.</p><p><strong>Conclusion: </strong>Our study further expands NEK1 genetic variability by identifying novel rare variants and confirming ALS oligogenic nature since 19.6% of NEK1 patients also carried mutations in one of the four main ALS-associated genes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"469"},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326079","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":"A meta-analysis of survival and prognostic factors in multiple system atrophy.","authors":"Xiao Dong, Daji Chen, Linlin Wan, Linliu Peng, Zhao Chen, Riwei Ouyang, Xiafei Long, Kefang Du, Xiaokang Wu, Xinying Xiao, Ruqing He, Rong Qiu, Beisha Tang, Hong Jiang","doi":"10.1007/s00415-025-13204-y","DOIUrl":"10.1007/s00415-025-13204-y","url":null,"abstract":"<p><strong>Background: </strong>Multiple-system atrophy is a rapidly progressive neurodegenerative disease with incomplete survival data, limiting the understanding of long-term outcomes. This study aimed to investigate a comprehensive data including survival time and prognostic factors.</p><p><strong>Methods: </strong>Individual patient data were pooled from studies reporting Kaplan-Meier curves, and then, survival curves were generated. The pooled median survival times were derived using weighted median of medians approach and hazard ratios of risk factors were analyzed using either fixed- or random-effects model.</p><p><strong>Results: </strong>37 studies involving 6145 patients were included. The median survival time for MSA patients was 8.23 years (95% CI 8.02-8.56) based on reconstructed individual patient data. The pooled weighted median time was 8.0 years (95% CI 7.51-9.0). The following variables were found as unfavorable prognostic factors (hazard ratio with 95% CI are shown): age at onset (1.02, 1.01-1.03), poor levodopa response (1.55, 1.14-2.11), parkinsonism onset (1.30, 1.05-1.62), falls (1.84, 1.4-2.4), dysautonomia onset (1.48, 1.16-1.9), autonomic failure (2.52, 1.42-4.48), orthostatism hypotension (1.39, 1.16-1.66), bladder catheterization (1.81, 1.41-2.31), and stridor (1.5, 1.12-2.02).</p><p><strong>Conclusion: </strong>Survival time in MSA was evaluated using multiple methodological approaches, revealing a median survival of 8.0 years, and clinical variables like early autonomic failure and frequently falls were identified as predictors of poor survival outcomes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"467"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326078","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":"Hypothalamic atrophy in CANVAS/RFC1.","authors":"Verena Miranda Souza, Camila Caroso Lobo, Thiago Junqueira Ribeiro Rezende, Gabriel Silva Schmitt, Paula Camila Alves de Assis Pereira Matos, Fabrício Diniz de Lima, Alberto Rolim Muro Martinez, Orlando Graziani Povoas Barsottini, José Luiz Pedroso, Wilson Marques, Marcondes Cavalcante França","doi":"10.1007/s00415-025-13194-x","DOIUrl":"https://doi.org/10.1007/s00415-025-13194-x","url":null,"abstract":"<p><strong>Background: </strong>Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a late-onset multisystem disorder related to the RFC1 gene. Despite evidence of dysautonomia and sleep disturbances, hypothalamic involvement is unknown.</p><p><strong>Objective: </strong>We aimed to investigate hypothalamic volumetry in CANVAS/RFC1.</p><p><strong>Methods: </strong>We analyzed 19 CANVAS/RFC1 patients and 19 healthy controls using automated hypothalamic segmentation from 3 T-MRI scans. Volumetric comparisons were performed using ANCOVA, while correlations with Scale for the Assessment and Rating of Ataxia (SARA) and Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT) scores were assessed by Pearson's correlation.</p><p><strong>Results: </strong>CANVAS/RFC1 group had a significantly lower total hypothalamic volume (RFC1: 734.84 ± 160.49 mm³ vs Controls: 878.83 ± 136.55 mm³; P = 0.03; d = 0.99) and a reduced left tuberal superior (LTS) volume (RFC1: 71.21 ± 21.85 mm³ vs Controls: 90.30 ± 15.67 mm³; P = 0.02; d = 0.99). LTS volume inversely correlated with SARA score (R = -0.51, P = 0.049), but no associations were found with SCOPA-AUT.</p><p><strong>Conclusion: </strong>This study reveals hypothalamic atrophy in CANVAS, suggesting its role in disease pathophysiology. Further research should investigate broader hypothalamic dysfunctions and clinical implications.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"465"},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317138","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":"\"How to save a marriage\": treatment of REM sleep behavior disorder (RBD) with acetyl-leucine in a patient with Parkinson's disease.","authors":"Wolfgang H Oertel, Martin T Henrich, Filip Bergquist, Annette Janzen, Fanni F Geibl, Michael Strupp","doi":"10.1007/s00415-025-13195-w","DOIUrl":"10.1007/s00415-025-13195-w","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"466"},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317137","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":"Clinical and therapeutic clues from a long-term follow-up: a single center experience on a large LOPD population.","authors":"Alessia Pugliese, Mattia Porcino, Selene Francesca Anna Drago, Giuseppe Trimarchi, Carmelo Rodolico, Olimpia Musumeci, Antonio Toscano","doi":"10.1007/s00415-025-13105-0","DOIUrl":"https://doi.org/10.1007/s00415-025-13105-0","url":null,"abstract":"<p><p>Pompe disease is an inherited metabolic disorder, caused by acid alpha-glucosidase (GAA) enzyme deficiency. Late-onset form (LOPD) usually presents with proximal and axial myopathy, followed by progressive respiratory involvement. Since 2006, enzyme replacement therapy (ERT) has been the gold standard treatment. Recently, two ERTs of second generation have been approved. Several studies have demonstrated the benefits of the first generation ERT (FG-ERT), although outcomes are quite variable, and very long-term data are limited. In fact, functional long-term studies are still needed to clearly point out the prolonged efficacy of FG-ERT. We describe a cohort of 49 LOPD patients, providing a very long-term follow-up of motor and pulmonary function of 30 of them treated by FG-ERT (from 2 to 20 years), using 6MWT, FVC, and GSGC score to evaluate patients' responses. 6MWT remained quite stable in the first 4 years of therapy, followed by a slow decline of its value of about 21%. FVC showed an improving trend in the first 4 years, followed by a decline of about 12%. Along the follow-up, GSGC score worsened with an increasing of about 30% of the total score values. Although long-term results evidenced variable therapeutic responses, the general trend is an improvement in motor and respiratory functions during the first 2-4 years of treatment, followed by a variable degree of decline. According to these results, and in line with recent EPOC recommendations, it is strongly suggested to start therapy in symptomatic patients, but also to carefully manage presymptomatic patients to timely supply ERT treatment.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"464"},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310056","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":"Is intravenous aciclovir overused in possible viral encephalitis? a retrospective review.","authors":"Anna Wakelin, Anthony Wolff, Heather Angus-Leppan","doi":"10.1007/s00415-025-13168-z","DOIUrl":"https://doi.org/10.1007/s00415-025-13168-z","url":null,"abstract":"<p><strong>Introduction: </strong>Timely administration of IV aciclovir reduces mortality in herpes simplex virus (HSV) encephalitis (Sköldenberg in Lancet, 1984), (Whitley in N Engl J Med, 1986). Early diagnosis, however, is challenging due to non-specific symptoms and delays in obtaining key investigation results. Empiric treatment with intravenous (IV) aciclovir in cases of suspected meningitis to cover for possible concurrent viral encephalitis is an approach not supported by the National Institute for Clinical Excellence (NICE) ( https://www.nice.org.uk/guidance/ng240 , 2024). Such practice exposes patients to the risk of iatrogenic nephrotoxicity and neurotoxicity.</p><p><strong>Methods: </strong>Our objectives were to evaluate the diagnostic approach to suspected viral encephalitis and appropriateness of aciclovir prescription. This was a retrospective cohort study of 410 patients over 16 years old prescribed IV aciclovir for suspected central nervous system infection at Royal Free London NHS Foundation Trust between December 2021 and February 2024.</p><p><strong>Results: </strong>29% of patients fulfilled diagnostic criteria for possible or probable encephalitis while 5% did not fulfil any of the criteria. 38% had no microbiological or serological testing for HSV or varicella zoster virus. Discharge diagnoses included 5% with viral encephalitis (2% confirmed on cerebrospinal fluid testing) and 6% with meningitis, while the commonest diagnosis was delirium (11% of patients).</p><p><strong>Discussion: </strong>While acknowledging clinical uncertainty and attendant risks of missing a diagnosis of true viral encephalitis, in line with NICE guidelines we suggest a review of routine prescription of IV aciclovir in suspected meningitis and emphasise the importance of altered mental status as a useful distinguishing feature between viral encephalitis and meningitis in immunocompetent patients.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"463"},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302265","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}