Journal of Neurology最新文献

{"title":"VEP latency delays predicts MRI neurodegenerative outcomes in multiple sclerosis.","authors":"Dejan Jakimovski, Joanna Weller, Robert Zivadinov, Bianca Weinstock-Guttman, Daniel Golan, Myassar Zarif, Fiona Costello, Robert C Sergott, Steven L Galetta, Rachel Kenney, Laura J Balcer, Wim Van Hecke, Dirk Smeets, Bishal Dhakal, Sarah A Morrow, Thomas J Covey, Mark Gudesblatt","doi":"10.1007/s00415-026-14151-y","DOIUrl":"10.1007/s00415-026-14151-y","url":null,"abstract":"<p><strong>Background: </strong>Visual evoked potential (VEP) P100 latency is routinely used to assess optic nerve demyelination. However, there is no established methodology for disentangling whether shifts in VEP P100 latency may reflect upstream changes in the visual pathway, such as the level of the retina, or whether these delays could be reflective of downstream disturbances in broader brain structure and functioning.</p><p><strong>Objective: </strong>To determine the relationship between VEP-based P100 and MRI-based outcomes in people with MS (PwMS) after accounting for structural retinal changes assessed by spectral domain optical coherence tomography (OCT).</p><p><strong>Methods: </strong>64 study participants underwent OCT, VEP, and MRI. Standardized VEP assessment derived monocular P100 latency for both eyes. Similarly, OCT performed on Heidelberg Spectralis hardware provided peripapillary retinal nerve fiber layer (pRNFL) thickness. Mediation analyses were performed to assess the relationship between P100 and MRI-based outcomes, adjusting for mediating effects of pRNFL and age.</p><p><strong>Results: </strong>VEP-based P100 was significantly associated with lower whole brain volume (WBV) (p=0.0037), with 87.8% of the total effect being both direct and independent from RNFL and the significant age-WBV covariate effect. Similarly, greater VEP-based P100 latency was directly and independently predictive of lower gray matter volume (GMV) (p=0.015) and greater T2-FLAIR LV (p=0.0036) after adjusting for RNFL and age mediating effects.</p><p><strong>Conclusion: </strong>VEP-based P100 latency shows both age- and RNFL-independent associations with MRI-based MS outcomes. In addition to their established diagnostic utility, VEP measures may provide a neurophysiological, objective metric to assess neurodegeneration.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061321","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":"Dorsal and ventral stream visuoperceptual processing deficits in Lewy body disease.","authors":"Emily McCann, Felicia Coleman, Soohyun Lee, Amir Fazlollahi, John D O'Sullivan, Peter J Nestor","doi":"10.1007/s00415-026-14166-5","DOIUrl":"10.1007/s00415-026-14166-5","url":null,"abstract":"<p><strong>Introduction: </strong>Hypometabolism of visual-processing cortices is the hallmark of dementia in Lewy body diseases (LBD) yet visuoperceptual impairments remain under-researched compared to other cognitive domains.</p><p><strong>Methods: </strong>Novel, sensitive measures of dorsal- and ventral-stream visual processing were developed and administered to n=53 LBD patients, spanning cognitively asymptomatic to dementia, and compared to n=29 Alzheimer's disease (AD) patients. Further analyses stratified LBD for visual hallucination status and contrasted visuoperceptual performance to measures of attention/executive function.</p><p><strong>Results: </strong>Visuoperceptual impairments were more prominent in LBD than AD, being detectable even in some that were cognitively asymptomatic. LBD demonstrated comparable ventral and dorsal impairments, whereas ventral visuoperceptual performance was relatively preserved compared to dorsal in AD. In LBD, visuoperceptual impairments were strongly associated with visual hallucination and explained a significant amount of performance on visually presented executive function/attention measures. The effect sizes of impairment in demented LBD were substantially larger on the novel visuoperceptual tests compared to standard non-visually presented tests of attention (Digit Span) and executive function (phonemic fluency).</p><p><strong>Discussion: </strong>Early dorsal and ventral stream impairments are a hallmark of dementia in LBD, differing quantitatively and qualitatively from AD. These deficits in LBD were more pronounced than those of attention and executive function.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061888","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":"Pharmacological treatment of sleep disorder phenotypes in Parkinson's disease: a systematic review and meta-analysis of randomised controlled trials.","authors":"Jaquelini Betta Canever, Laura Cechinel da Silva, Fernanda Samara Apio, Helena Iturvides Cimarosti","doi":"10.1007/s00415-026-14158-5","DOIUrl":"10.1007/s00415-026-14158-5","url":null,"abstract":"<p><strong>Background: </strong>Sleep disturbances are amongst the most prevalent and disabling non-motor symptoms in Parkinson's disease (PD), encompassing excessive daytime sleepiness (EDS), poor sleep quality, insomnia, and REM sleep behaviour disorder (RBD). The pharmacological evidence base remains fragmented across phenotypes, drug classes, and outcome instruments.</p><p><strong>Objectives: </strong>To evaluate the efficacy and safety of pharmacological interventions for sleep disorders in PD, stratified by sleep phenotype, through a systematic review and meta-analysis of randomised controlled trials (RCTs).</p><p><strong>Methods: </strong>Six databases were searched without restrictions. Eligible studies were RCTs in adults with PD and any sleep disturbance. Pooling was performed using random-effects models. Risk of bias was assessed with the Cochrane RoB 2 tool. The protocol was registered in PROSPERO (CRD420261412614).</p><p><strong>Results: </strong>Twenty-nine RCTs (1913 participants; 2002 to 2025) were included. Only 17.2% of trials were at low overall risk of bias. For EDS (k = 6), the pooled ESS estimate was directionally favourable but non-significant (MD 1.75; 95% CI -0.26 to 3.75; I² = 91%), driven predominantly by a single influential crossover trial. For overall sleep quality (k = 6), pharmacological treatment produced a statistically significant improvement in PSQI scores (MD 2.66; 95% CI 1.63 to 3.69; I² = 71%). For insomnia symptoms (k = 3) and RBD (k = 2), pooled estimates were non-significant with high heterogeneity (I² = 96% and 99%, respectively), precluding reliable conclusions. Given this level of heterogeneity (I² > 90%), pooled estimates for these two domains, as well as for EDS, are presented as exploratory only and narrative synthesis is emphasised over meta-analytic pooling. No unexpected safety signals were identified, although safety reporting was heterogeneous and quantitative pooling was not performed.</p><p><strong>Conclusions: </strong>Pharmacological treatment, particularly with chronobiotic agents and dopaminergic receptor agonists, may produce improvement in overall sleep quality (low-certainty evidence). Evidence for EDS, insomnia symptoms, and RBD remains insufficient for definitive recommendations, and pooled estimates in these domains should not be over-interpreted given their very high statistical heterogeneity. Phenotype-specific RCTs with harmonised outcome measures are needed.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039268","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 link between plasma and cognitive markers for Alzheimer's disease in Down syndrome: a longitudinal study.","authors":"Alberto Fernández, Elisa M Molanes-López, Pilar Zuluaga, Lucía Vaquero, Fernando Moldenhauer, José M Galván-Román, Ricardo Bajo, Natalia Lagunas, Javier García-Alba","doi":"10.1007/s00415-026-14165-6","DOIUrl":"10.1007/s00415-026-14165-6","url":null,"abstract":"<p><strong>Background: </strong>Given the need to clarify the relationship between biomarkers, cognitive performance, and clinical status in Down syndrome (DS), this longitudinal study examined the influence of baseline clinical diagnosis on the evolution of plasma neurofilament light (NfL) and p-tau217, as well as the predictive value of baseline cognitive performance on biomarker trajectories and clinical conversion within the Alzheimer's disease (AD) continuum.</p><p><strong>Methods: </strong>57 adults with DS were classified as asymptomatic (A_DS; n = 25), prodromal (P_DS; n = 16), or dementia (D_DS; n = 16). Clinical, neuropsychological, and biomarker assessments were conducted at baseline and after a 24-month follow-up.</p><p><strong>Results: </strong>Biomarker levels increased significantly over time in pathological groups only, with the greatest increase observed in the D_DS group. Baseline performance on the New Serial Learning Immediate test (NSL_I) was the strongest predictor of biomarker evolution. Each one-point increase in baseline NSL_I score was associated with a reduction of 0.035 units in the longitudinal increase of p-tau217 and 0.463 units in NfL. Baseline p-tau217 values were the only significant predictor of clinical conversion: individuals with values one unit above the sample median showed a 3.56-fold increased risk of progression to a more advanced clinical stage.</p><p><strong>Conclusion: </strong>These findings highlight the relevance of episodic memory performance as a predictor of biomarker progression, particularly p-tau217, and support its close association with clinical status and disease progression. The results support the development of screening strategies to identify DS individuals at high risk of rapid cognitive decline and to inform future therapeutic trials.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039337","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":"What have trials targeting amyloid in Alzheimer's told us to date? The conversation the Alzheimer's field isn't having.","authors":"Adrian M Owen","doi":"10.1007/s00415-026-14147-8","DOIUrl":"10.1007/s00415-026-14147-8","url":null,"abstract":"<p><p>A recent systematic review concluded that anti-amyloid therapies for Alzheimer's disease offer no clinically meaningful benefit, drawing sharp criticism that focused largely on the review's methodology rather than on the clinical case for the drugs themselves. This Comment examines what the currently licensed treatments deliver for patients and what terms, such as 'modest' and 'moderate', benefit mean in practical and clinical terms.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039258","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":"Frequency-Specific EEG burst dynamics in Parkinson's Disease and freezing of gait.","authors":"Matthew Leedom, Md Rezwanul Akter Pallab, Vishal Bharmauria, Oliver Flouty, Samuel Stuart, Martina Mancini, Arun Singh","doi":"10.1007/s00415-026-14149-6","DOIUrl":"10.1007/s00415-026-14149-6","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) disrupts motor networks, but conventional EEG spectral analyses may miss the transient, burst-like structure of pathological oscillations. Freezing of gait (FOG) is a disabling and poorly understood gait disturbance that may involve altered cognitive-motor control. This study aims to determine whether resting-state electroencephalography burst dynamics provide frequency-specific markers of PD and FOG.</p><p><strong>Methods: </strong>Resting-state EEG was analyzed from 237 participants across three study sites, including 88 healthy controls and 149 individuals with PD assessed in the clinically defined ON-medication state. Participants with PD were also classified as having FOG (PDFOG +) or not having FOG (PDFOG -). Analyses were harmonized across sites using 11 common EEG channels. Burst dynamics were quantified in theta, alpha, low-beta, and high-beta bands using amplitude-envelope thresholding. Primary analyses focused on low- and high-beta burst dynamics at mid-frontal lead for healthy controls vs PD comparisons, and theta, low-beta, and high-beta burst dynamics for healthy control, PDFOG-, and PDFOG+ comparisons. FOG severity associations were examined using a study site-standardized FOGQ z-scores.</p><p><strong>Results: </strong>People with PD showed altered low-beta burst timing, characterized by more frequent, but shorter low-beta bursts compared with healthy controls. These effects were evident at the mid-frontal region and supported by exploratory topographic maps. In three-group analyses, low-beta burst rate and duration differed across groups, but adjusted PD-only models did not support robust PDFOG+ vs PDFOG- differences. In contrast, FOG severity was most consistently associated with theta amplitude-related burst metrics.</p><p><strong>Conclusions: </strong>Resting-state EEG burst dynamics reveal dissociable oscillatory signatures in PD. Low-beta burst timing abnormalities reflect general PD-related motor network dysfunction, whereas theta burst amplitude may relate to FOG severity and cognitive-motor network burden.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030784","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":"Horatio C. Wood (1841-1920).","authors":"Lazaros C Triarhou","doi":"10.1007/s00415-026-14129-w","DOIUrl":"10.1007/s00415-026-14129-w","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030836","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":"Theodore H. Weisenburg (1876-1934).","authors":"Lazaros C Triarhou","doi":"10.1007/s00415-026-14120-5","DOIUrl":"10.1007/s00415-026-14120-5","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025179","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":"Charles K. Mills (1845-1931).","authors":"Lazaros C Triarhou","doi":"10.1007/s00415-026-14114-3","DOIUrl":"10.1007/s00415-026-14114-3","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025138","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":"Real-world neuropsychiatric safety profile of foslevodopa/foscarbidopa infusion in advanced Parkinson's disease.","authors":"Giulia Lazzeri, Roberta Zangaglia, Carlo Fazio, Elena Contaldi, Salvatore Bonvegna, Simone Regalbuto, Simone Malaspina, Gianni Pezzoli, Alice Jacqueline Mariangela Jelmoni, Silvia Piazza, Francesca Valentino, Luca Magistrelli, Ioannis Ugo Isaias, Antonio Pisani","doi":"10.1007/s00415-026-14113-4","DOIUrl":"10.1007/s00415-026-14113-4","url":null,"abstract":"<p><strong>Background: </strong>To describe demographic, clinical, and neuropsychiatric safety outcomes in a cohort of PD patients treated with LDp/CDp infusion in a real-world setting.</p><p><strong>Methods: </strong>We retrospectively analyzed a database of 77 consecutive PD patients treated with LDp/CDp at two Italian tertiary referral centers, with a minimum 6-month follow-up. Baseline cognitive, epidemiological, and clinical variables were assessed to determine potential neuropsychiatric adverse event (NAE) risk factors.</p><p><strong>Results: </strong>Patients had long disease duration (13.8±6.4 years) and moderate-to-severe motor burden (MDS-UPDRS III: 34.4±15). Pre-existing cognitive impairment (MCI 41.6%, dementia 7.8%), prior hallucinations (26%), and impulse control disorders (27.3%) were frequent. At 6 months, mean L-dopa equivalent daily dose increased by ~300 mg (p<0.001). The dropout rate was 16.9% (13 patients), mainly due to AEs (38.5%), bridging to DBS (23%), or device intolerance (15.4%). New-onset NAEs emerged in 17 patients (22.1%) at a median of 30 days, predominantly hallucinations (41.2%) and psychosis (29.4%). Most events were efficiently managed via careful infusion rate adjustments and low-dose antipsychotics, achieving resolution or improvement in 82% of cases. Three patients (18%) discontinued therapy due to severe NAEs. Multivariable regression analysis confirmed baseline Frontal Assessment Battery (FAB) score as the primary independent predictor of NAE development (OR 0.707, p=0.010).</p><p><strong>Conclusions: </strong>LDp/CDp infusion is well-tolerated. Although NAEs were more frequent than in pivotal trials, they were largely manageable. Frontal executive dysfunction emerged as a significant risk factor, suggesting specific frontal screening should be routine in candidacy evaluation for cognitively frail patients. Preventive strategies to reduce risk are proposed and discussed.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017067","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}