Journal of Neurology最新文献

{"title":"Clinical features and prognosis of EGPA-associated peripheral neuropathy: a multicentre REVEAL cohort study.","authors":"Yuichi Masuda, Shogo Matsuda, Ayana Okazaki, Ryosuke Tsuge, Atsushi Manabe, Tomoki Taniguchi, Ryosuke Hiwa, Muneyuki Hatta, Mayu Shiomi, Ryu Watanabe, Naoko Suwa, Youhei Fujiki, Hirofumi Miyake, Wataru Yamamoto, Motomu Hashimoto, Tohru Takeuchi, Takuya Kotani","doi":"10.1007/s00415-026-14196-z","DOIUrl":"10.1007/s00415-026-14196-z","url":null,"abstract":"<p><strong>Objectives: </strong>Peripheral neuropathy (PN) is a severe manifestation of eosinophilic granulomatosis with polyangiitis (EGPA). However, the aetiology of PN in EGPA remains unclear. This study aimed to elucidate the clinical characteristics and prognosis of patients with EGPA with PN using a multicentre database in Japan.</p><p><strong>Methods: </strong>Newly diagnosed patients with EGPA between 2006 and 2024 were enrolled in this study. EGPA was diagnosed according to the ACR/EULAR 2022 classification criteria. Initial clinical characteristics were compared between patients with EGPA with and without PN based on BVAS ver. 3.0. The recurrence rate of PN in EGPA patients with neuropathy was also investigated, and risk factors for PN relapse were identified.</p><p><strong>Results: </strong>Of the 159 patients enrolled in the REVEAL cohort, 107 newly diagnosed and treatment-naïve patients with EGPA were included. MPO-ANCA was positive in 45 patients (42.1%) and 93 patients (86.9%) had PN. The levels of WBC, eosinophil granulocyte, serum immunoglobulin (Ig)G, and serum IgG4 were significantly higher in patients with EGPA with PN than in those without PN. Among them, IgG4 was the most useful clinical indicator for detecting PN in patients with EGPA. Kaplan-Meier estimator showed that 5-year relapse rate of PN among patients with EGPA with PN was 18.6%. The administration rate of intravenous cyclophosphamide (IVCY) was significantly lower in patients with relapse of PN than in those without relapse of PN.</p><p><strong>Conclusion: </strong>Serum IgG4 might be a useful clinical indicator for detecting PN in EGPA and IVCY administration might be effective in preventing PN relapse.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110621","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":"Neuroimaging signatures of facial onset sensory and motor neuronopathy (FOSMN).","authors":"Angela Rosenbohm, Francisco Herrera-Angeles, Hans-Jürgen Huppertz, Karl Georg Haeusler, Jochen H Weishaupt, Hans-Peter Müller, Jan Kassubek","doi":"10.1007/s00415-026-14174-5","DOIUrl":"10.1007/s00415-026-14174-5","url":null,"abstract":"<p><p>Facial onset sensory and motor neuronopathy (FOSMN) is an exceptionally rare condition characterized by progressive facial paresthesia and the subsequent appearance of bulbar symptoms with rostro-caudal motor and sensory deficits sometimes extending to the hand muscles. The pathophysiological understanding of this disorder is very limited. In order to identify patterns of neuroanatomical involvement within the brain, we applied advanced magnetic resonance imaging-based techniques to a group of six patients with the diagnosis of FOSMN, using unbiased analysis techniques with atlas-based volumetry of volume-rendering T1-weighted data and whole brain-based spatial statistics of diffusion tensor imaging (DTI). The volumetric data showed significant global atrophy with prominent involvement of the medulla oblongata, while DTI demonstrated significant decreases in the right-hemispheric frontal lobe and bilaterally along the superior and inferior longitudinal fasciculi. In summary, this application of volumetry and DTI to a group of FOSMN patients demonstrated, beyond global brain atrophy as a correlate of a systemic disease process, regional atrophy in the brainstem/medulla oblongata, together with tract alterations of polymodal frontotemporoparietal interconnections. Future neuroimaging studies in larger patient groups of FOSMN are needed for detailed phenotype-neuroimaging correlations.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111075","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":"Incidence of Progression Independent of Relapse Activity (PIRA) under platform disease-modifying treatment in multiple sclerosis.","authors":"Leonardo Palazzo, Ferdinando Clarelli, Antonino Giordano, Laura Ferré, Lucia Moiola, Maria A Rocca, Federica Esposito, Massimo Filippi","doi":"10.1007/s00415-026-14171-8","DOIUrl":"10.1007/s00415-026-14171-8","url":null,"abstract":"<p><strong>Background: </strong>Comparative data on the impact of platform disease-modifying therapies (DMTs) on Progression Independent of Relapse Activity (PIRA) in patients with remitting-relapsing MS (RRMS) are limited. We compared the risk of PIRA among RRMS patients treated with oral (dimethyl fumarate [DMF] versus teriflunomide [TER]) and injectable (interferon beta [IFN] versus glatiramer acetate [GA]) therapies in a real-world setting.</p><p><strong>Methods: </strong>We conducted a retrospective study including RRMS patients from the Italian MS Registry treated for ≥ 5 years with DMF, TER, IFN, or GA. PIRA was defined as confirmed disability worsening sustained for ≥ 12 months in the absence of relapses. Propensity score 1:1 matching was applied separately for each comparison. Negative binomial regression and Cox models assessed cumulative PIRA events and time to first PIRA event, respectively.</p><p><strong>Results: </strong>Among 1910 eligible patients, 174 matched pairs were obtained for DMF vs TER and 404 matched pairs for IFN vs GA. No significant differences emerged in the cumulative incidence of PIRA (RR:0.82; 95% CI:0.47-1.40), or time to first PIRA (HR:0.81; 95% CI: 0.47-1.37) in TER- versus DMF-treated patients, as well as in GA- versus IFN-treated patients (RR:1.04; 95% CI:0.74-1.45; HR:0.86; 95% CI:0.63-1.17). In pooled comparison between injectable and oral DMTs, no significant differences emerged (RR:0.79; 95% CI:0.52-1.19; HR:1.06; 95% CI:0.71-1.58).</p><p><strong>Conclusions: </strong>Platform DMTs showed no statistically significant differences on PIRA. Treatment selection within platform DMTs should therefore rely primarily on safety and tolerability considerations rather than expectations of differential protection against relapse-independent progression.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110925","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":"Cerebrospinal fluid inflammatory proteomic profiling identifies biomarkers linked to disease progression in amyotrophic lateral sclerosis.","authors":"Congwen Lv, Wenjia Zhu, Xinmei Wen, Yaye Wang, Nairong Xie, Haoran Liu, Yuting Jiang, Wenlong Zou, Qinyao Liu, Junjiu Gou, Xiaotong Yu, Li Di, Yan Lu, Min Wang, Min Xu, Hai Chen, Jianying Duo, Yue Huang, Yuwei Da","doi":"10.1007/s00415-026-14178-1","DOIUrl":"10.1007/s00415-026-14178-1","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is a key component of amyotrophic lateral sclerosis (ALS), but its association with disease progression heterogeneity remains unclear. We aimed to identify CSF inflammation-related proteins associated with disease progression phenotype in patients with ALS.</p><p><strong>Methods: </strong>Patients with ALS were stratified into slow progressors (SP) and fast progressors (FP) according to the disease progression rate. CSF inflammatory proteins were measured using the Olink Target 96 Inflammation panel. Disease-associated biomarkers were identified using limma package and elastic net (EN) analysis. We assessed the discriminatory power of disease-associated biomarkers using receiver operating characteristic curve analysis and estimated the optimism-adjusted area under the curve (AUC) using the bootstrapping method.</p><p><strong>Results: </strong>Among 77 patients (SP: n=40; FP: n=37), limma analysis identified 11 differentially expressed proteins, with functional enrichment in chemokine signaling, TNF-related responses and NF-κB pathways. EN analysis identified 12 candidate proteins, among which CST5, CCL11, SIRT2, CD6, CCL4, MMP-1, TNFRSF9, CCL19, and MCP-4 showed positive associations with the SP phenotype. A model combining SIRT2, MMP-1, BMI, and site of onset yielded an apparent area under the curve of 0.769 (95% CI 0.662 to 0.876) and an optimism-corrected area under the curve of 0.729.</p><p><strong>Conclusion: </strong>Our study uncovered a CSF inflammatory proteomic signature associated with slow disease progression in ALS. These findings indicate that specific CSF neuroinflammatory protein signatures reflect biological heterogeneity in ALS disease progression rather than non-specific neurodegeneration. SIRT2 and MMP-1 warrant further investigation as components of progression-stratification models, although validation in larger, longitudinal, and independent cohorts is required.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110598","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":"Melvin Yahr (1917-2004).","authors":"Hélio A Ghizoni Teive, Léo Coutinho, Alex Tiburtino Meira, Carlos Henrique Ferreira Camargo","doi":"10.1007/s00415-026-14184-3","DOIUrl":"10.1007/s00415-026-14184-3","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111092","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":"Multimodal PET-MRI profiling predicts dementia with Lewy bodies in isolated REM sleep behaviour disorder.","authors":"Andreas Myhre Baun, Alex Iranzo, Miriam Højholt Terkelsen, Rainer Hinz, Morten Gersel Stokholm, Mónica Serradell, Kristina Bacher Svendsen, Alicia Garrido, Dolores Vilas, Arne Møller, Carles Gaig, Eduardo Tolosa, David J Brooks, Per Borghammer, Simon Fristed Eskildsen, Nicola Pavese","doi":"10.1007/s00415-026-14176-3","DOIUrl":"10.1007/s00415-026-14176-3","url":null,"abstract":"<p><p>Despite isolated REM sleep behaviour disorder (iRBD) reliably identifying individuals at high risk of developing Parkinson's disease (PD) or dementia with Lewy bodies (DLB), with more than 90% converting, the neurobiological markers of the conversion phenotype are not fully understood. Most previous studies have found univariate imaging biomarkers of phenoconversion, and most of these lack specificity for PD and DLB. Using a well-characterised iRBD cohort (N=21), receiving multiple PET and MRI scans, we aimed to assess if the inter-modality relationship can specifically predict conversion to PD or DLB. The patients received [¹⁸F]-DOPA, [¹¹C]-Donepezil and [¹¹C](R)-PK11195 PET and structural MRI scans to derive grey matter (GM) volume along with dynamic susceptibility contrast MRI to extract measures of microcirculatory dysregulation. We used a multimodal adaptation of the scaled sub-profile model to identify patterns of multimodal covariance across the PET and MRI scans. We identified a multimodal network characterised by high neuroinflammation, cholinergic dysfunction, GM atrophy and microcirculatory dysfunction with the covariance pattern converging in the medial occipito-parietal cortex (OPC). The combined pathology from the OPC and striatal [¹⁸F]-DOPA uptake was able to specifically predict conversion into DLB (sub-distribution hazard ratio=38.68, 95% confidence interval: 7.545-198.3), and this survived correction for age and disease duration. These findings demonstrate the feasibility of integrating multiple modalities in risk assessment and suggest that posterior cortical pathology, along with striatal dopaminergic impairment, could hold predictive value for phenotype-specific conversion of iRBD patients, and that multiple pathological processes converge in this brain region.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111109","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":"Non-motor symptoms burden and motor recovery following STN-DBS in Parkinson's disease: a data-driven longitudinal analysis.","authors":"Ghadir Abbas, Robert Peach, Uchralt Temuulen, Yunyou Tang, Tanmoy Sil, Anna Kufner, Matthias Endres, Jens Volkmann, Florian Lange, Martin Reich","doi":"10.1007/s00415-026-14160-x","DOIUrl":"https://doi.org/10.1007/s00415-026-14160-x","url":null,"abstract":"<p><strong>Background: </strong>Subthalamic nucleus-deep brain stimulation (STN-DBS) reliably improves cardinal motor symptoms in Parkinson's disease (PD). However, gait disorders and non-motor symptoms (NMS) may persist or emerge following surgery, diminishing quality of life and complicating clinical management.</p><p><strong>Objectives: </strong>To characterize the dominant axes of clinical covariance across motor and non-motor domains before and after STN-DBS, and to determine whether non-motor symptom severity moderates post-DBS gait and mobility change.</p><p><strong>Methods: </strong>100 PD patients undergoing STN-DBS (mean age 60.2 ± 7.6 years; 67% male) were studied. Principal component analysis (PCA) was performed on thirteen motor and non-motor sub-scores at pre-DBS, 1-year follow-up (1-y FU), and a subset (n = 33) at 3-5-year follow-up. Moderation was tested using analysis of covariance (ANCOVA): each 1-year motor outcome was regressed on its pre-DBS baseline, a non-motor moderator, and their interaction, adjusting for age and disease duration, with a significant interaction indicating that baseline non-motor severity was associated with the degree of subsequent motor recovery.</p><p><strong>Results: </strong>PCA identified a core motor triad: gait, mobility, and freezing of gait as the primary source of clinical variance at all timepoints (PC1: 35% pre-DBS, declining to 28% at 3-5-y FU), PC1 was the only component to exceed a permutation null (p < 0.001), with memory-related impairment increased at longer-term follow-up. Moderation analysis showed that higher pre-operative mood burden specifically for psychomotor and psychosomatic symptoms were associated with poorer recovery of mobility (Psychomotor β = 1.16, p < 0.05). At 1-y FU anxiety and psychosomatic symptoms showed concurrent associations with mobility and overall motor burden (Anxiety β = 2.30, p < 0.05).</p><p><strong>Conclusions: </strong>STN-DBS outcomes extend beyond global motor improvement and may be shaped by associations spanning the motor, cognitive, and mood domains. Higher NMS baseline burden was associated with poorer mobility recovery, and mood symptoms at follow-up were associated with concurrent motor burden. These exploratory findings support considering multi-domain pre-operative assessment and post-operative mood monitoring, as potential targets for optimizing motor outcomes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111036","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":"Spinal cord imaging in multiple sclerosis: from diagnosis to disease progression.","authors":"Tal J Koren, Jashan Dugal, Dongang Wang, Heidi Beadnall, Chenyu Tim Wang, Yael Barnett, Fernando Calamante, Xavier Montalban, Jiwon Oh, Michael H Barnett","doi":"10.1007/s00415-026-14122-3","DOIUrl":"https://doi.org/10.1007/s00415-026-14122-3","url":null,"abstract":"<p><p>Spinal cord (SC) involvement in multiple sclerosis (MS) is common and a major determinant of long-term disability in both relapsing and progressive disease phenotypes. Despite this, SC pathology remains under-assessed in both clinical practice and therapeutic trials, largely due to technical challenges inherent to spinal SC magnetic resonance imaging (MRI) conferred by the cord's small anatomical size and sensitivity to physiological motion and susceptibility artefact. This review synthesises current understanding of SC involvement in MS, integrating advances in pathophysiology, imaging, and clinical application. We describe the characteristic MRI features of MS SC lesions and their key inflammatory and non-inflammatory differentials, and examine the role of SC imaging in diagnosis, particularly in the context of the 2024 revisions to the McDonald criteria. We highlight the prognostic importance of SC lesions and atrophy, including their association with progression independent of relapse activity, and review the limited and heterogeneous evidence regarding the effects of disease-modifying therapies on SC pathology. We further evaluate current MRI acquisition strategies and consensus guidelines, and discuss emerging quantitative and advanced imaging techniques that detect microstructural and biochemical abnormalities beyond conventional imaging. Together, these developments support a more systematic integration of SC imaging into MS clinical care and trial design.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"273 10","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111027","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":"Stroke mimic caused by severe hypomagnesemia: a case report and literature review.","authors":"David Vidal Bankier, Francis Renard, Mario Manto","doi":"10.1007/s00415-026-14155-8","DOIUrl":"10.1007/s00415-026-14155-8","url":null,"abstract":"<p><p>Association of hypomagnesemia and neurological deficits is a well documented issue, but despite its importance, magnesium levels are rarely tested during the acute phase of a stroke. Focal neurological deficits have rarely been ascribed to hypomagnesemia. We report the case of a patient treated with Proton Pump Inhibitors and Metformin with a history of unexplained transient neurological deficits who developed stroke-like symptoms of hemiparesis and aphasia with recovery after correction of his hypomagnesemia. We also present a brief literature review regarding Magnesium's role in focal neurological deficits.</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":"149081133","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":"Preliminary insights into whole-blood mitochondrial DNA copy number and telomere length in Parkinson's disease and multiple system atrophy.","authors":"Monica Gagliardi, Alessia Felicetti, Radha Procopio, Antonio Augimeri, Maurizio Morelli, Andrea Quattrone, Grazia Annesi, Aldo Quattrone","doi":"10.1007/s00415-026-14172-7","DOIUrl":"10.1007/s00415-026-14172-7","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) and multiple system atrophy (MSA) are α-synucleinopathies characterized by progressive neurodegeneration and overlapping clinical features but distinct pathological mechanisms with peripheral biomarkers remaining limited. Mitochondrial dysfunction and telomere attrition are hallmarks of cellular aging implicated in neurodegeneration, yet their combined role remains unclear.</p><p><strong>Methods: </strong>Whole-blood mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) were assessed in 58 PD patients, 35 MSA patients, and 62 healthy controls from Southern Italy. Mitochondrially encoded NADH dehydrogenase 1 (ND1) gene levels and TL were measured by quantitative PCR and normalized to the β-actin gene. Group differences were tested using multivariable linear regression adjusted for age and sex, with statistical significance defined as p < 0.05 after false discovery rate (FDR)-corrected Wald tests.</p><p><strong>Results: </strong>ND1-CN was significantly reduced in PD (p_FDR = <math><mrow><mn>1.63</mn> <mo>×</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>22</mn></mrow> </msup> </mrow> </math> ) and MSA (p_FDR = <math><mrow><mn>2.56</mn> <mo>×</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>8</mn></mrow> </msup> </mrow> </math> ) compared to controls and was also significantly lower in PD with respect to MSA (p_FDR = <math><mrow><mn>8.43</mn> <mo>×</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>22</mn></mrow> </msup> </mrow> </math> ). TL was reduced in PD (p_FDR = <math><mrow><mn>3.21</mn> <mo>×</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>16</mn></mrow> </msup> </mrow> </math> ) and MSA (p_FDR = <math><mrow><mn>1.44</mn> <mo>×</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>12</mn></mrow> </msup> </mrow> </math> ), with smaller between-group differences (p_FDR = <math><mrow><mn>5.47</mn> <mo>×</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>2</mn></mrow> </msup> </mrow> </math> ).</p><p><strong>Conclusions: </strong>Our findings support the involvement of mitochondrial dysfunction and telomere attrition in PD and MSA. However, mtDNA-CN provided a clearer distinction between the two α-synucleinopathies than TL, suggesting that peripheral mtDNA-CN may represent a more informative non-invasive biomarker of disease-specific mitochondrial alterations. Further longitudinal studies in larger, independent cohorts are warranted to validate its diagnostic and prognostic utility.</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":"149081156","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}