Journal of Neurology最新文献

{"title":"Scleromyxedema-Associated Myopathy and Vacuolar Myopathy with Monoclonal Gammopathy and Stiffness (VAMMGAS) as manifestations of Monoclonal Gammopathy of Clinical Significance (MGCS): a disease spectrum between autophagy dysfunction and inflammation.","authors":"Tommaso Nicoletti, Olivier Benveniste, Maxime Battistella, Thibault Mahevas, Bertrand Arnulf, Tanya Stojkovic, Katia Staedler, Thierry Maisonobe, Franck Letournel, Pierre Romero, Edoardo Malfatti, Marguerite Vignon, Aleksandra Nadaj-Pakleza, Beatrice Labella, Emmanuelle Lacene, Guy Brochier, Teresinha Evangelista, Sarah Leonard-Louis","doi":"10.1007/s00415-026-14169-2","DOIUrl":"10.1007/s00415-026-14169-2","url":null,"abstract":"<p><p>Scleromyxedema-Associated Myopathy (SAM) and Vacuolar Myopathy with Monoclonal Gammopathy and Stiffness (VAMMGAS) are rare clinical entities associated with Monoclonal Gammopathy of Clinical Significance (MGCS). We compared the clinical, neurophysiological, histopathological, and ultrastructural features of three patients (two with SAM and one with VAMMGAS), together with a review of the available literature, to further characterize the similarities and differences between these two conditions. Our analysis suggests that SAM and VAMMGAS may represent part of a clinical spectrum characterized by progressive proximal muscle weakness and prominent pathological spontaneous activity on electromyography. By definition, SAM is associated with scleromyxedema, which may occasionally develop after the onset of myopathy, whereas VAMMGAS is characterized by muscle stiffness. The underlying monoclonal gammopathy is most commonly IgG ? in SAM, while IgG ? appears to be more frequent in VAMMGAS. Histopathologically, both conditions show a myopathy with features suggestive of impaired autophagy and evidence of immune activation (abnormal HLA-I expression and sarcolemmal C5b-9 deposits), although inflammatory infiltrates appear to be more characteristic of SAM, providing insights into potentially shared pathogenic mechanisms. Taken together, these findings support the concept that SAM and VAMMGAS may represent related manifestations within the spectrum of MGCS-associated muscle disease. Recognition of their overlapping clinical, neurophysiological, and histological features may facilitate diagnosis and broaden our understanding of the underlying pathophysiological mechanisms, potentially informing therapeutic strategies. Importantly, both conditions appear to be treatable with immunomodulatory approaches (including intravenous immunoglobulins and plasma exchange) as well as clone-directed therapies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081179","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":"Progressive motor impairment from intracerebral critical demyelinating lesions.","authors":"Purnashree Chowdhury, Eoin P Flanagan, Yong Guo, W Oliver Tobin, Bianca Albites Coen, Claudia F Lucchinetti, Brian G Weinshenker, Orhun H Kantarci, B Mark Keegan","doi":"10.1007/s00415-026-14168-3","DOIUrl":"10.1007/s00415-026-14168-3","url":null,"abstract":"<p><strong>Background: </strong>Focal critical demyelinating lesions anatomically associated with progressive motor impairment are described in multiple sclerosis (MS) and restricted demyelinating diseases, typically within the spinal cord lateral column and ventral cervicomedullary junction (CMJ). This study describes such lesions within the intracerebral corticospinal tracts.</p><p><strong>Methods: </strong>We retrospectively reviewed people seen at Mayo MS Clinic (2002-2025) with progressive central nervous system demyelinating disease and progressive (≥ 1 year) upper motor neuron weakness anatomically associated with a presumed demyelinating lesion of the cerebral white matter, internal capsule, or upper brainstem, excluding alternative spinal cord or CMJ lesions. Demographics, disease course, Expanded Disability Status Scale (EDSS), MS disease-modifying therapy use, brain and spinal cord magnetic resonance imaging, cerebrospinal fluid studies and neuropathology findings were reviewed.</p><p><strong>Results: </strong>Seventeen people had an intracerebral critical demyelinating lesion: cerebral white matter in 12 (70%), internal capsule in 3 (18%) and upper brainstem in 2 (12%). Ten were female, and all were white. Progression from onset course was 13 (76%) and from relapse onset was 4 (24%). Median, interquartile range (IQR) for age at progressive motor impairment onset was 46 (IQR 38-52) years, and EDSS at last evaluation was 5.5 (IQR 4.0-5.5). Sixteen (94%) had progressive spastic hemiparesis and 1 (6%) monoparesis. Cognitive impairment occurred in 6/12 (50%) and seizures in 3/12 (25%) with cerebral white matter critical lesions. Abnormal intrathecal production of immunoglobulin G markers was consistent with MS in 10/15 (66%). Neuropathology confirmed demyelination in 4/6 biopsies.</p><p><strong>Conclusions: </strong>Intracerebral critical demyelinating lesions associated with progressive motor impairment can rarely occur along the corticospinal tracts of the brain.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074387","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":"Interlocking pentagons task and visuospatial deficit in parkinsonian syndrome: a quantitative approach.","authors":"Giulia Donzuso, F Cilio, E Ferrante, C D'Agate, G Fazzina, C E Cicero, G Mostile, A Nicoletti, M Zappia","doi":"10.1007/s00415-026-14163-8","DOIUrl":"10.1007/s00415-026-14163-8","url":null,"abstract":"<p><strong>Objectives: </strong>Visuo-spatial impairment is a common feature in parkinsonian disorders and differentiating idiopathic Parkinson's disease (PD) from atypical parkinsonian syndromes (APS), i.e. progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD), remains a major clinical challenge. The Qualitative Scoring Pentagon Test (QSPT), derived from the MMSE pentagon-copying item, provides quantitative visuo-constructive assessment but has not been systematically evaluated as a differential marker in parkinsonism. Aim of the study was to assess the discriminative value of the QSPT total score and sub-items across parkinsonian syndromes, and to examine associations with neuropsychological tests, motor severity, and MRI morphometric indices.</p><p><strong>Methods: </strong>Patients with PD and APS were enrolled and underwent clinical and neuropsychological evaluations including MMSE, Frontal Assessment Battery (FAB), Trail Making Test (TMT-A), and MDS-Unified Parkinson's Disease Rating Scale-Section III (MDS-UPDRS-III). A group of healthy controls (HC) were also enrolled performing MMSE. Pentagon drawings were scored quantitatively (QSPT). When available, MRI morphometric features were collected. Statistical analysis were performed to assess associations between QSPT, cognitive and clinical features, and to evaluate differences between patients and HC and across patients' groups.</p><p><strong>Results: </strong>One-hundred and forty patients (PD=91, PSP=23, MSA=17, CBD=9) and 92 HC were enrolled. QSPT differed significantly considering HC performances (12.7 ± 0.5) versus patients groups, and across groups (p<0.001), with PD scoring the highest (11.5 ± 2.1) and CBD the lowest score (7.7 ± 4.4). PD differed from PSP (p<0.001), CBD (p<0.001) and MSA (p=0.040). Rotation and number-of-angles sub-items were the most discriminating features. QSPT significantly correlated with MMSE, FAB, TMT-A, and MRPI (all p<0.01). Multivariate models demonstrated that QSPT was independently associated with APS (OR=0.620, 95%CI 0.469-0.820, p<0.001). A QSPT score ≤ 8 points discriminated PD from APS with an AUC of 0.764 and a specificity of 92.3%, and ≤ 11 points discriminated synucleinopathies from tauopathies with a higher AUC (0.804).</p><p><strong>Conclusion: </strong>This study demonstrates that quantitative scoring of the MMSE pentagon-copying item could differentiate PD from APS. The presence of association between QSPT and MRI brainstem morphometry could also reflect a structural association, specifically identifying tauopathies. QSPT could be a simple and supportive clinical tool, embedded within the MMSE that could differentiates patients from HC and PD from APS.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074447","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":"Intravenous thrombolysis use before interhospital transfer for thrombectomy: a systematic review and meta-analysis.","authors":"Zixin Wang, Yun Chen, Jiamin Li, Boyi Yuan, Wan Wang, Jiameng Li, Qingfeng Ma","doi":"10.1007/s00415-026-14173-6","DOIUrl":"10.1007/s00415-026-14173-6","url":null,"abstract":"<p><strong>Aims: </strong>Intravenous thrombolysis (IVT) before interhospital transfer for endovascular thrombectomy (EVT) in patients with large-vessel occlusion acute ischemic stroke (LVO-AIS) remains controversial. We aimed to evaluate the efficacy and safety of pre-transfer IVT in LVO-AIS patients who presented to primary stroke centers (PSCs) and required transfer to comprehensive stroke centers (CSCs) for EVT.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, and ClinicalTrials.gov from inception to July 2, 2026. Studies comparing IVT versus no IVT prior to interhospital transfer for EVT in patients with LVO-AIS were included. Efficacy outcomes included the primary outcome of excellent functional outcome (modified Rankin Scale [mRS] 0-1 at 90 days), as well as secondary efficacy outcomes including good functional outcome (mRS 0-2 at 90 days), interhospital recanalization, and poor functional outcome (mRS 5-6). Safety outcomes included 90-day mortality, symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and parenchymal hematoma (PH). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models, and adjusted estimates were synthesized using the generic inverse variance method.</p><p><strong>Results: </strong>Sixteen observational studies were included. Pre-transfer IVT was associated with significantly higher rates of excellent functional outcome (OR 1.72, 95% CI 1.47-2.01, p<0.00001), good functional outcome (OR 1.64, 95% CI 1.35-1.99, p<0.00001), and interhospital recanalization (OR 7.71, 95% CI 4.08-14.55, p<0.00001), as well as significantly lower risks of poor functional outcome (OR 0.65, 95% CI 0.54-0.79, p<0.0001) and 90-day mortality (OR 0.69, 95% CI 0.59-0.81, p<0.00001). No significant differences were observed between groups in the risks of sICH (OR 0.75, 95% CI 0.50-1.11, p=0.15), any ICH (OR 0.91, 95% CI 0.76-1.09, p=0.31), or PH (OR 1.43, 95% CI 0.88-2.33, p=0.15). In the adjusted analyses, the associations remained significant for excellent functional outcome (aOR 1.47, 95% CI 1.19-1.81, p=0.0004), good functional outcome (aOR 1.61, 95% CI 1.25-2.07, p=0.0002), interhospital recanalization (aOR 8.06, 95% CI 4.71-13.82, p<0.00001), and 90-day mortality (aOR 0.64, 95% CI 0.49-0.84, p=0.001). The magnitude and direction of associations were generally consistent with the unadjusted analyses.</p><p><strong>Conclusion: </strong>Among LVO-AIS patients requiring interhospital transfer from PSCs to CSCs for EVT, pre-transfer IVT was associated with improved functional outcomes and interhospital recanalization, without increasing hemorrhagic risk. These findings support pre-transfer IVT as an effective reperfusion strategy in resource‑limited settings where timely EVT is not immediately accessible.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074453","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-space navigation in patients with focal epilepsy underpins the prominent role of the hippocampus for allocentric navigation in humans.","authors":"Denis Grabova, Elisabeth Kaufmann, Cauchy Pradhan, Jan Rémi, Christian Vollmar, Ilias Masouris, Elisabeth Wlasich, Julia Kustermann, Andreas Zwergal, Florian Schöberl","doi":"10.1007/s00415-026-14164-7","DOIUrl":"10.1007/s00415-026-14164-7","url":null,"abstract":"<p><strong>Background: </strong>An in-depth assessment of spatial navigation in patient cohorts with focal brain disorders may inform about the functional topography of underlying brain networks. The aim of the current study was to investigate the role of the right and left hippocampi on recombining novel routes in a real-space environment as a correlate for allocentric navigation abilities in patients with focal epilepsies.</p><p><strong>Methods: </strong>In a single-center approach, adults with unifocal epilepsy were prospectively recruited from the tertiary epilepsy center at LMU Munich. 16 patients with right-sided mesial temporal lobe epilepsy (rTLE), 16 with left-sided mesial temporal lobe epilepsy (lTLE), 15 with frontal lobe epilepsy (FLE), and 24 age-matched healthy controls conducted a real-space navigation paradigm that required recognition of familiar routes and recombination of novel routes. Visual exploration behavior and navigation trajectories were documented by a gaze-controlled head-fixed camera and analyzed post hoc across groups and navigation conditions.</p><p><strong>Results: </strong>Epilepsy patients (mean age 40.7 years) performed significantly worse in finding navigation targets than controls (p<0.001). Age, duration of epilepsy, and structural brain lesions affected navigation performance. After correcting for confounders, rTLE patients showed significantly inferior performance compared to FLE, especially for recombined novel routes. lTLE patients were impaired mainly on recombined novel routes. rTLE patients spent more time at crossroads and used shortcuts less often than controls.</p><p><strong>Conclusion: </strong>This study supports the hippocampus as a major hub for human goal-oriented navigation in real environments, with right hippocampal dysfunction particularly impairing allocentric navigation and creation of novel routes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069625","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 role of leukocyte p38 MAP kinase in immune-mediated peripheral polyneuropathies: distinct modulation by intravenous immunoglobulins.","authors":"Marina Stamenkovic, Irena Vukovic, Emina Milosevic, Stojan Peric, Aleksandar Paunic, Aleksandra Anicin, Ivana Basta, Ivo Bozovic, Aleksa Palibrk, Vukan Ivanovic, Vladimir Trajkovic, Verica Paunovic","doi":"10.1007/s00415-026-14106-3","DOIUrl":"10.1007/s00415-026-14106-3","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are rare immune-mediated peripheral polyneuropathies with insufficiently elucidated etiopathogenesis. Mitogen activated protein kinases (MAPK), the intracellular energy sensor AMP-activated protein kinase (AMPK), and the master metabolic regulator mechanistic target of rapamycin complex 1 (mTORC1) regulate immune responses through various mechanisms, including autophagy.</p><p><strong>Methods: </strong>We used immunoblotting to analyze AMPK/mTORC1 signaling, autophagy, and the activation status of the MAPK family members p38, extracellular signal-regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK) in peripheral blood mononuclear cells (PBMC) of 17 treatment-naïve CIDP patients and 7 MMN patients already on chronic intravenous immunoglobulin (IVIg) therapy.</p><p><strong>Results: </strong>Compared with age/sex-matched controls, PBMC from CIDP and MMN patients showed higher levels of active (phosphorylated) p38 MAPK, whereas autophagy and AMPK/mTORC1, ERK, and JNK pathways were not significantly altered. The amounts of p38 MAPK in PBMC negatively correlated with muscle strength in MMN, but not CIDP. The treatment of CIDP patients (n = 9) with IVIg did not affect the activation status of AMPK, MAPK, or autophagy in PBMC. In contrast, IVIg treatment reduced the phosphorylation of p38 MAPK, ERK, and AMPK in PBMC from MMN patients (n = 6), and the decrease in phospho-p38 MAPK levels correlated with improved hand grip strength.</p><p><strong>Conclusions: </strong>Together, this exploratory study indicates that leukocyte p38 MAPK modulation might be involved in disease activity and therapeutic effect of IVIg in MMN, but not CIDP.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069676","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":"Evaluating the neurofilament light chain-derived gap between biological and chronological age in multiple sclerosis and controls.","authors":"Valerio Nicolella, Carmela Polito, Vincenzo Criscuolo, Marco Varelli, Stefania Fasano, Mariano Fiorenza, Gennaro Pascarella, Antonio Carotenuto, Maria Petracca, Roberta Lanzillo, Giuseppe Castaldo, Vincenzo Brescia Morra, Francesco Salvatore, Daniela Terracciano, Marcello Moccia","doi":"10.1007/s00415-026-14157-6","DOIUrl":"10.1007/s00415-026-14157-6","url":null,"abstract":"<p><strong>Objective: </strong>To compare chronological age and neurofilament light chain (NfL)-derived age in people with multiple sclerosis (pwMS) and controls, and to explore clinical correlates of the NfL age gap.</p><p><strong>Methods: </strong>We conducted a real-world, retrospective analysis including 792 pwMS (without evidence of clinical or MRI activity in the previous year and during follow-up) and 302 controls. NfL-derived age was computed using established age-adjusted reference. We used logistic regression models to compare pwMS and controls in chronological and NfL-derived age groups, and linear regression models to evaluate the associations of chronological age and NfL-derived age with clinical variables (Expanded Disability Status Scale (EDSS), disease duration, disease course, disease modifying treatment (DMT) class, number of previous DMTs) and the associations between the NfL age gap (difference between biological and chronological age) and clinical variables.</p><p><strong>Results: </strong>PwMS showed a higher likelihood than controls of having a NfL-derived age above their chronological age (OR = 1.44;95%CI 1.10-1.87; p = 0.007). EDSS, disease duration, and progressive disease course were associated with both chronological and NfL-derived age (all p < 0.001). The NfL age gap showed independent associations with EDSS (Coeff = 0.147; 95%CI 0.097-0.197; p < 0.001), progressive disease course (Coeff = 0.34; 95%CI 0.16-0.53; p < 0.001), and number of previous DMTs (Coeff = 0.06; 95% CI 0.01-0.11; p = 0.028), but not with disease duration or DMT class. Similar results were observed in a sub-analysis excluding pwMS with EDSS progression.</p><p><strong>Conclusions: </strong>MS is associated with a shift in age-associated NfL trajectory, with an older biological profile especially in pwMS with greater disability and progressive course.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069715","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":"Late-onset CMT neuropathy in the NGS era: a 10-year retrospective study.","authors":"Etienne Fortanier, Nathalie Bonello-Palot, Annie Verschueren, Ludivine Kouton, Aude-Marie Grapperon, Emmanuelle Salort-Campana, Giovanni Corazza, Virginie Milhe de Bovis, Luce Barbat du Closel, Emilien Delmont, Shahram Attarian","doi":"10.1007/s00415-026-14154-9","DOIUrl":"10.1007/s00415-026-14154-9","url":null,"abstract":"<p><strong>Background and aim: </strong>Late-onset Charcot-Marie-Tooth (CMT) disease remains under-recognized and may mimic acquired neuropathies in older adults. We aimed to determine the prevalence and clinical, electrophysiological, and genetic characteristics of genetically confirmed late-onset CMT and to identify features distinguishing it from late-onset non-CMT neuropathies.</p><p><strong>Methods: </strong>We retrospectively reviewed all patients who underwent next-generation sequencing (NGS) for suspected hereditary neuropathy between 2015 and 2025 at a single neuromuscular referral center. Late-onset CMT was defined by symptom onset after 50 years and a class 5 pathogenic variant. Clinical, electrophysiological, genetic, and functional data were collected. Patients were compared with a 2:1 age- and sex-matched control group with late-onset neuropathies, negative CMT-targeted NGS, and a confirmed alternative diagnosis.</p><p><strong>Results: </strong>Among 642 patients tested after age 50, 57 had genetically confirmed late-onset CMT (8.9%). Pes cavus (80.7%) and a family history of neuropathy (63.2%) were the most frequent clinical features, while disability remained mild. Pathogenic variants involved 20 genes, with a 32% prevalence of PMP22 duplication and frequent involvement of MME, LRSAM1, MPZ, and MFN2. The main alternative diagnoses were inflammatory, idiopathic axonal, and toxic neuropathies. Compared with controls (n = 114), family history, pes cavus, and median nerve conduction velocity < 38 m/s were independently associated with late-onset CMT in multivariate analyses.</p><p><strong>Discussion: </strong>Late-onset CMT accounts for a substantial proportion of neuropathies after age 50. Family history, pes cavus, and slowed median nerve conduction should prompt comprehensive genetic testing, particularly including genes associated with late-onset phenotypes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061886","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":"Leisure-time physical activity, sun exposure, and multiple sclerosis risk: a population-based case-control study.","authors":"Qingyuan Guo, Tomas Olsson, Lars Alfredsson, Anna Karin Hedström","doi":"10.1007/s00415-026-14170-9","DOIUrl":"10.1007/s00415-026-14170-9","url":null,"abstract":"<p><strong>Background: </strong>Physical activity benefits symptoms and function in people with multiple sclerosis (MS), but its relevance to MS susceptibility remains uncertain and may be difficult to separate from correlated lifestyle and environmental factors, including sun exposure.</p><p><strong>Methods: </strong>This Swedish population-based case-control study included 3,008 incident MS cases and 5773 matched controls. Analyses were restricted to participants whose MS onset, or corresponding reference year among controls, occurred within 5 years before study inclusion. Leisure-time physical activity 5 years before inclusion was classified into four levels. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression overall and by sun exposure. Time spent outdoors was additionally considered in a subgroup.</p><p><strong>Results: </strong>In models adjusted for age, sex, and residential area, the highest versus lowest level of physical activity was associated with lower MS risk (OR 0.78, 95% CI 0.67-0.92), but the association was attenuated after multivariable adjustment (OR 0.94, 95% CI 0.80-1.11). High physical activity was associated with lower risk among individuals with low sun exposure (adjusted OR 0.76, 95% CI 0.58-0.99), whereas no association was observed among those with high sun exposure (adjusted OR 0.97, 95% CI 0.78-1.20). In the subgroup, additional adjustment for outdoor activity had little influence on the estimates.</p><p><strong>Conclusion: </strong>The overall association between leisure-time physical activity and MS risk was attenuated after adjustment for lifestyle and environmental factors. Inverse associations among individuals with low sun exposure and in analyses accounting for outdoor activity suggest a possible context-dependent association.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060873","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":"Family history of multiple sclerosis and long-term outcomes.","authors":"Anna Karin Hedström, Tomas Olsson, Lars Alfredsson","doi":"10.1007/s00415-026-14162-9","DOIUrl":"10.1007/s00415-026-14162-9","url":null,"abstract":"<p><strong>Background: </strong>Family history is a well-established risk factor for multiple sclerosis (MS), but its influence on disease progression remains unclear. We investigated whether familial MS, including degree of relatedness, is associated with baseline characteristics and disease outcomes.</p><p><strong>Methods: </strong>We included individuals with incident MS from the Swedish population-based epidemiologic investigation of multiple sclerosis study with longitudinal follow-up through the Swedish MS registry. Participants were categorized as having no family history of MS, first-degree familial MS, or second-/third-degree familial MS. Outcomes included confirmed disability worsening (CDW), progression to Expanded Disability Status Scale milestones 3 and 4, cognitive worsening measured by the symbol digit modalities test, MRI disease activity, and worsening on the Multiple Sclerosis Impact Scale-29. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression.</p><p><strong>Results: </strong>Among 3,094 participants, 239 (7.7%) reported a first-degree relative with MS and 468 (15.1%) reported a second-/third-degree relative with MS. Baseline characteristics were similar across groups, although HLA-DRB1*15:01 positivity was more common among individuals with first-degree familial MS. No significant associations were observed between familial MS status and disability progression, cognitive decline, MRI disease activity, or patient-reported worsening. Compared with individuals without a known family history of MS, the HR for CDW was 1.06 (95% CI 0.89-1.30) among individuals with first-degree familial MS and 1.04 (95% CI 0.90-1.20) among those with second-/third-degree familial MS.</p><p><strong>Conclusions: </strong>Family history of MS did not appear to have a substantial prognostic impact on long-term disease outcomes after MS onset.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061898","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}