Journal of Neurology最新文献

{"title":"DAGLA autoantibody experience at Mayo Clinic.","authors":"Nisa Vorasoot, Cigdem Isitan-Alkawadri, Bharat Pillai, Ramona Miske, Divyanshu Dubey, Michael Gilligan, Stefanie Hahn, John Mills, Sean J Pittock, Anastasia Zekeridou, Andrew McKeon","doi":"10.1007/s00415-025-13197-8","DOIUrl":"10.1007/s00415-025-13197-8","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"460"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285029","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":"Prospective quantitative evaluation of gait and stance in patients with acute vertigo and dizziness.","authors":"Hristo Hadzhikolev, Ken Möhwald, Patricia Jaufenthaler, Max Wuehr, Klaus Jahn, Andreas Zwergal","doi":"10.1007/s00415-025-13191-0","DOIUrl":"10.1007/s00415-025-13191-0","url":null,"abstract":"<p><strong>Background: </strong>Patients with acute vertigo and dizziness often suffer from gait ataxia and postural imbalance. However, detailed and quantitative investigations of gait and stance are largely missing during the acute stage of symptoms.</p><p><strong>Methods: </strong>This study explores whether assessing objective gait and stance parameters can help differentiate between peripheral and central causes of isolated acute vertigo and dizziness. Patients underwent a standardized protocol within the EMVERT study at the emergency department of LMU University Hospital during the acute stage (on average at 16 h after symptom onset), which included the Timed Up and Go test (TUG), Functional Gait Assessment (FGA), Gait and Truncal Ataxia Index (GTI) and mobile posturography. Patients were categorized into three groups: Acute vestibular strokes (n = 56), acute unilateral vestibulopathy (AUVP, n = 52) and episodic vestibular disorders (n = 92). Outcomes were analyzed using logistic regression models and ROC curves adjusted for age and sex.</p><p><strong>Results: </strong>We found that patients with AUVP exhibited worse TUG, FGA and GTI scores than those with vestibular strokes or episodic vestibular disorders. ROC curves for TUG, FGA and GTI showed a weak diagnostic accuracy (0.57-0.62) for stroke versus AUVP, which only improved (to 0.75-0.82), if corrected for age and gender. Posturographic sway path was lowest for episodic vestibular disorders, but similar for stroke and AUVP.</p><p><strong>Conclusion: </strong>Clinical gait and stance tests such as TUG, FGA and GTI do not reliably differentiate central from peripheral etiologies of isolated acute vertigo and dizziness in patients with a mild to moderate burden of symptoms.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"458"},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275078","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":"Complement activation profiles in patients with immune checkpoint inhibitor-associated neuromuscular immune-related adverse events.","authors":"Leonie Müller-Jensen, Nora Möhn, Thomas Skripuletz, Sophia Carl, Janin Thomas, Lea Grote-Levi, Sandra Nay, Philipp Ivanyi, Imke von Wasielewski, Ralf Gutzmer, Carsten Dittmayer, Werner Stenzel, Samuel Knauss, Matthias Endres, Jan D Lünemann, Wolfgang Boehmerle, Petra Huehnchen","doi":"10.1007/s00415-025-13181-2","DOIUrl":"10.1007/s00415-025-13181-2","url":null,"abstract":"<p><strong>Background: </strong>Immune-related neuropathy (irNeuropathy) and myositis (irMyositis) are the most common neurologic adverse events (irAE-n) associated with immune checkpoint inhibitors. Although case reports suggest benefits of complement inhibitors, the role of complement activation in irAE-n is understudied.</p><p><strong>Methods: </strong>In a retrospective multicenter study, we enrolled patients with irNeuropathy or irMyositis, cancer controls (CCs), and healthy controls (HCs). Serum levels of 11 complement components were measured using multiplex enzyme-linked immunosorbent assays. Associations with irAE-n severity and outcomes were assessed by Spearman's correlation. C5b-9-positive complement deposition was analyzed in muscle and nerve specimens from a subset of patients.</p><p><strong>Results: </strong>Thirty-one irMyositis patients, 25 irNeuropathy patients, 25 CCs, and 17 HCs were included. Complement component levels were elevated in irNeuropathy (C3a, C5a, sC5b-9, C3, Ba, C4a), irMyositis (C3a, Ba), and CCs (C3a, C5a, sC5b-9, Bb, Ba, C4a), compared to HCs. In irMyositis, higher levels of C5a and complement regulators Factor H and I correlated with lower irAE-n severity (p = 0.02, rho = -0.45; p = < 0.01, rho = -0.56; p = < 0.001, rho = -0.67, respectively), and improved outcomes (p = 0.03, rho = -0.42; p = 0.05, rho = -0.40; p = < 0.001, rho = -0.64, respectively). Subtle C5b-9 deposition was detected in all tissue samples but showed non-specific patterns.</p><p><strong>Discussion: </strong>Systemic complement activation is detectable in cancer patients regardless of irAE-n status, and tissue complement deposition is unspecific. Our findings suggest that complement activation is not a major driver of irAE-n, leaving the therapeutic potential of complement inhibitors uncertain.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"459"},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285028","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":"Changes in corticosteroid and non-steroidal immunosuppressive therapy with long-term zilucoplan treatment in generalized myasthenia gravis.","authors":"Channa Hewamadduma, Miriam Freimer, Angela Genge, M Isabel Leite, Kimiaki Utsugisawa, Tuan Vu, Babak Boroojerdi, Fiona Grimson, Natasa Savic, Mark Vanderkelen, James F Howard","doi":"10.1007/s00415-025-13113-0","DOIUrl":"10.1007/s00415-025-13113-0","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of complement component 5 inhibitor zilucoplan in patients with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG) were assessed in two double-blind studies (NCT03315130/NCT04115293 [RAISE]). During these studies and the first 12 weeks of the open-label extension study, RAISE-XT, corticosteroid and non-steroidal immunosuppressive therapy (NSIST) doses were kept stable; thereafter doses could be changed at the investigator's discretion. We evaluated corticosteroid and NSIST dose changes in patients with gMG during zilucoplan treatment in RAISE-XT.</p><p><strong>Methods: </strong>In RAISE-XT, patients who completed a qualifying double-blind study self-administered once-daily subcutaneous zilucoplan 0.3mg/kg. We assessed (post hoc) patients who changed their corticosteroid or NSIST dose relative to double-blind baseline at Week 120 (data cutoff: November 11, 2023).</p><p><strong>Results: </strong>Overall, 200 patients enrolled. At Week 120, 61.1% (n = 33/54) of patients who were on corticosteroids at double-blind baseline had reduced or discontinued corticosteroids (mean 15.5mg dose reduction); mean change from baseline (CFB) in Myasthenia Gravis Activities of Daily Living (MG-ADL) score:-6.55 (standard deviation [SD] 3.65). Of patients on NSIST at double-blind baseline, 29.8% (n = 14/47) reduced or discontinued ≥ 1 NSIST; mean CFB in MG-ADL score:-7.57 (SD 4.69). Among all patients at Week 120, 9.3% (n = 8/86) had increased or started corticosteroids; 2.4% of patients (n = 2/85) had increased NSIST, including one who started a new NSIST. Zilucoplan was well tolerated.</p><p><strong>Conclusions: </strong>Treatment with zilucoplan allowed for reduction or discontinuation of corticosteroids in the majority of patients and NSIST in about a third of patients, while maintaining efficacy.</p><p><strong>Trial registration: </strong>NCT04225871; October 2, 2019.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"457"},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275066","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":"Burden of pathogenetic and likely pathogenetic variants in SPG7, SPG11 and AP4 genes in Amyotrophic Lateral Sclerosis. A case-control study.","authors":"Paolo Niccolò Doronzio, Serena Lattante, Daniela Bernardo, Agata Katia Patanella, Giulia Bisogni, Emiliana Meleo, Elda Del Giudice, Davide Colavito, Lucia Maria Porro, Eleonora Sabatelli, Amelia Conte, Marcella Zollino, Mario Sabatelli, Giuseppe Marangi","doi":"10.1007/s00415-025-13164-3","DOIUrl":"10.1007/s00415-025-13164-3","url":null,"abstract":"<p><strong>Background: </strong>There is evidence that some Hereditary Spastic Paraplegia (HSP) genes are linked to Amyotrophic Lateral Sclerosis (ALS). In particular, KIF5A and SPG11 genes, which cause two different forms of HSP, are also associated with adult-onset and Juvenile ALS, respectively.</p><p><strong>Objectives: </strong>To study the frequencies of pathogenetic and likely pathogenetic variants in HSP genes in ALS patients and to determine whether they act as predisposing factors.</p><p><strong>Methods: </strong>We analysed 72 HSP-associated genes in 1024 ALS and 44 Primary Lateral Sclerosis patients and applied customized ACMG criteria to identify pathogenic and likely pathogenic variants. Based on the frequency of identified variants, six genes, including SPG7, SPG11 and the four genes encoding the subunits of the AP4 adaptor protein, were selected for analysis in an additional cohort of 481 ALS patients. Overall results on 1549 patients were compared with 1138 controls.</p><p><strong>Results: </strong>The frequency of variants in SPG7 gene was 0.45% (7/1549) in patients vs 0.18% (2/1138) in controls (p = 0.19), in SPG11 was 0.77% (12/1549) in cases and 0.26% (3/1138) in controls (p = 0.06), in AP4 genes was 0.64% (10/1549) in patients and 0.26% (3/1138) in controls (p = 0.13). The total number of variants detected across SPG7, SPG11 and AP4 genes was statistically different between patients and controls (1.87% vs 0.7%; p = 0.006).</p><p><strong>Conclusions: </strong>We found a significant enrichment of variants in a set of HSP genes, including SPG7, SPG11 and AP4 genes, in a large cohort of ALS patients, suggesting that they may act as predisposing factors for ALS.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"455"},"PeriodicalIF":4.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266377","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":"Patent foramen ovale diagnosis in young stroke patients: analysis of recurrence and mortality.","authors":"Eva Giralt-Steinhauer, Elisa Cuadrado-Godia, Ana Rodriguez-Campello, Isabel Fernández-Pérez, Daniel Guisado-Alonso, Adrià Macias-Gómez, Marta Vallverdú-Prats, Julia Peris-Subiza, Sergio Vidal-Notari, Mireia Ble-Gimeno, Jordi Jiménez-Conde, Angel Ois, Joan Jiménez-Balado","doi":"10.1007/s00415-025-13178-x","DOIUrl":"10.1007/s00415-025-13178-x","url":null,"abstract":"<p><strong>Background: </strong>Revised European Stroke Organization guidelines in 2018 recommend early patent foramen ovale (PFO) detection and closure in patients aged 60 or younger who suffered an ischemic stroke. Our primary aim was to analyze the impact of these guidelines on the detection of PFO. Our secondary endpoints were to investigate the differences in the risk of recurrence and mortality among PFO status.</p><p><strong>Methods: </strong>We conducted a population-based, retrospective cohort study in Catalonia using linked health administration databases. We included all ischemic stroke patients aged 18-60 from 2016 to 2021, collecting PFO diagnosis, demographics, comorbidities, stroke recurrence, and mortality.</p><p><strong>Results: </strong>A total of 13,780 individuals suffered an ischemic stroke, representing a raw annual incidence rate of 30.3 cases-per-100,000 inhabitants/year. PFO was detected in 749(5.4%), and these were younger, and had a lower prevalence of risk factors than patients without PFO (all p value < 0.05). After adjusting for age and sex, PFO diagnoses increased by 59% following the guidelines update. Five-year recurrence was 12.1% [95%CI 11.3-12.9] with no differences by age and PFO. Socioeconomical status and diabetes emerged as predictors of recurrence. Stroke patients with PFO showed a lower mortality rate (p value = 0.016). However, when stratified by age, PFO was linked to lower 4-year mortality only in patients ≤ 50 years.</p><p><strong>Conclusions: </strong>We confirm a greater detection of PFO in real-world practice following the update of guidelines. Regarding the risk of recurrence, socioeconomic status and diabetes were the only independent predictors of new stroke events. Additionally, we found a lower all-cause mortality in younger patients with PFO.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"456"},"PeriodicalIF":4.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275077","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 impact of autoimmune comorbidities on the onset attack recovery in adults with AQP4-NMOSD and MOGAD.","authors":"Sara Samadzadeh, Fiona Chan, Anna Francis, Layana Sani, Friedemann Paul, Nasrin Asgari, M Isabel Leite, Ruth Geraldes, Jacqueline Palace","doi":"10.1007/s00415-025-13180-3","DOIUrl":"10.1007/s00415-025-13180-3","url":null,"abstract":"<p><strong>Background: </strong>Aquaporin-4 neuromyelitis optica spectrum disorder (AQP4-NMOSD) often coexists with other autoimmune diseases (AIDs), whereas such comorbidities are less common in myelin oligodendrocyte glycoprotein antibody disease (MOGAD). This study investigates the impact of additional AIDs on early relapse recovery and disability in patients with AQP4-NMOSD and MOGAD.</p><p><strong>Methods: </strong>This retrospective study included patients aged > 16 years with AQP4-NMOSD (n = 175) or MOGAD (n = 221), who were followed at a nationally commissioned Oxford service and categorized based on the presence of at least one AID. Outcomes included recovery from the onset attack, visual recovery after the first optic neuritis (ON) attack (≥ 6 months post attack), time to first relapse and time to death. Incomplete visual recovery was defined as visual acuity worse than LogMAR 0.1. Optical coherence tomography (OCT) assessed retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer volume in a subset.</p><p><strong>Results: </strong>In the AQP4-NMOSD cohort, 28% (n = 49) had at least one AID, compared to 11.3% (n = 25) in the MOGAD cohort (p < 0.001), with thyroid disease constituting the majority of these cases in both groups. In MOGAD, the median age of first attack was significantly higher in the AID group (46 years; IQR: 35-56) than in the non-AID group (35 years; IQR: 28-47) (p = 0.004), a difference that was not observed in the AQP4-NMOSD cohort. In both the AQP4-NMOSD (n = 175) and the MOGAD (n = 221) cohorts, age was a significant predictor of outcome in univariate analyses (AQP4-NMOSD: OR = 0.96 per year, 95% CI: 0.94-0.98, p < 0.001; MOGAD: OR = 0.97 per year, 95% CI: 0.94-0.99, p = 0.008). No significant differences were observed in clinical or visual recovery rates between AID and non-AID patients in either cohort. There were no statistically significant differences observed between AID and non-AID cohorts for clinical or visual recovery outcomes. Similarly, AID status did not influence time to relapse (AQP4-NMOSD: HR = 1.0, 95% CI: 0.63-1.58, p = 0.99; MOGAD: HR = 0.78, 95% CI: 0.40-1.52, p = 0.47) or time to death (AQP4-NMOSD: HR = 0.5, 95% CI: 0.18-1.36, p = 0.28). OCT analysis revealed no significant differences in retinal parameters between AID and non-AID groups in both cohorts.</p><p><strong>Conclusions: </strong>Additional autoimmune diseases are unlikely to significantly affect clinical or visual outcomes in early attacks in patients with AQP4-NMOSD and MOGAD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"453"},"PeriodicalIF":4.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266379","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":"Retinal neuronal loss and progression independent of relapse activity in multiple sclerosis.","authors":"Federico Burguet Villena, Nuria Cerdá-Fuertes, Lisa Hofer, Sabine Schädelin, Shaumiya Sellathurai, Kean Schoenholzer, Marcus D'Souza, Johanna Oechtering, Henner Hanssen, Konstantin Gugleta, Alessandro Cagol, Cristina Granziera, Ludwig Kappos, Axel Petzold, Paskal Benkert, Jens Kuhle, Athina Papadopoulou","doi":"10.1007/s00415-025-13185-y","DOIUrl":"10.1007/s00415-025-13185-y","url":null,"abstract":"<p><strong>Background: </strong>In multiple sclerosis (MS), inner retinal thinning measured by optical coherence tomography (OCT) is related to lesional and gray matter changes of the brain.</p><p><strong>Objective: </strong>To evaluate the association between OCT markers and progression independent of relapse activity (PIRA).</p><p><strong>Methods: </strong>Analysis within the Swiss MS Cohort Study, in patients with ≥ 1 OCT. Mean thicknesses of: peripapillary retinal nerve fiber- (pRNFL), macular ganglion cell-inner plexiform- (mGCIPL), and inner nuclear layers (mINL) were assessed, excluding asymmetric eyes. PIRA was investigated during ≥ 4 years before the OCT. The associations of retinal layers with PIRA rates were estimated in linear regression adjusted for disease duration, age at onset, sex, body mass index, treatment and annualized relapse rate. In a sensitivity analysis, we investigated the associations between retinal layers and PIRMA rates (PIRA without activity on magnetic resonance imaging).</p><p><strong>Results: </strong>One hundred seventy one pwMS were included (median age: 51 years(y), Expanded Disability Status Scale: 2.5, pRNFL:94 µm, mGCIPL:67.2 µm, mINL:35.4 µm, observation time:8.1y). Sixty-seven patients (39%) showed PIRA. Mean pRNFL and mGCIPL thickness decreased respectively by - 2.28 µm (95% CI [- 4.32;- 0.24], p = 0.029) and - 1.70 µm (95% CI [- 2.97;- 0.42], p = 0.010) for each PIRA event per decade, while mINL (beta = - 0.33, CI: [- 0.75;0.1] p = 0.133) did not show significant associations with PIRA. In the sensitivity analysis, all three OCT measures were associated with PIRMA (pRNFL: beta = - 3.70, 95% CI [- 6.23; - 1.17], p = 0.005; mGCIPL: beta = - 2.49, 95% CI [- 4.12; - 0.87], p = 0.003), mINL: beta = - 0.58, 95% CI [- 1.11; - 0.05], p = 0.031).</p><p><strong>Conclusion: </strong>Our findings underline the role of retinal thinning measured by OCT as sensitive marker of progression in pwMS.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"454"},"PeriodicalIF":4.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266378","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":"Osteopontin levels in the serum reflect anatomical disease progression in patients with amyotrophic lateral sclerosis.","authors":"Tommaso Russo, Teuta Domi, Paride Schito, Yuri Matteo Falzone, Laura Pozzi, Massimo Locatelli, Nilo Riva, Edoardo G Spinelli, Federica Agosta, Massimo Filippi, Angelo Quattrini","doi":"10.1007/s00415-025-13190-1","DOIUrl":"10.1007/s00415-025-13190-1","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) lacks biomarkers for diagnosis, prognostic stratification, and evaluation of response to potential treatments. Previous research supported the role of serum osteopontin (OPN) levels as a potential biomarker in ALS. However, the associations of OPN serum levels with clinical features and their trend over the disease course have not been explored yet.</p><p><strong>Methods: </strong>We measured OPN serum levels in a retrospective cohort of 110 well-characterized patients with ALS, using a commercial ELISA kit, and analyzed their association with demographic and clinical features, as well as with other serum biomarkers. For a subset of patients, longitudinal measurements were available.</p><p><strong>Results: </strong>OPN serum levels differed significantly between patients with ALS and a cohort of 45 age and sex-matched healthy controls. However, when considering potential differential diagnoses, elevated OPN serum levels were not specific for ALS. Patients with an advanced disease stage (King's stage 3 or 4) exhibited significantly higher OPN serum levels compared to patients at earlier disease stages, whereas we did not observe any correlation with ALSFRS-R and progression rate. We observed an inverse correlation between OPN serum levels and BMI at diagnosis. Higher OPN serum levels predicted a shorter survival time and a shorter time to King's stage 4. No significant association between serum OPN and serum neurofilament light or glial fibrillary acid protein levels was observed. OPN serum levels were substantially stable over a 9-month observation time.</p><p><strong>Conclusion: </strong>Our findings indicate that serum OPN is an informative biomarker in ALS, providing valuable prognostic insights, potentially reflecting the extent of disease, and demonstrating potential applications in clinical trials.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"452"},"PeriodicalIF":4.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258292","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":"Neuropathological examination of 12 cases of familial Parkinson's disease with LRRK2 I2020T mutation including tau and TDP-43 pathology.","authors":"Akiko Uchino, Kazuko Hasegawa, Saburo Yagishita, Makiko Nagai, Mieko Ogino, Yutaka Ogino, Hiroyuki Hatsuta, Shigeo Murayama, Yuko Saito","doi":"10.1007/s00415-025-13148-3","DOIUrl":"10.1007/s00415-025-13148-3","url":null,"abstract":"<p><p>We previously reported a clinicopathological examination in the Sagamihara family, familial PD with LRRK I2020T mutation, highlighting the most common neuropathological finding as pure nigral degeneration without Lewy bodies (LBs). We applied immunohistochemical analysis to seven previously reported cases and evaluated five additional cases for a full neuropathological examination (altogether 12 cases). All cases exhibited nigral degeneration with a relatively preserved locus coeruleus (LC). Synuclein pathology was found in four cases, one of which showed multiple system atrophy pathology, and three showed LB pathology. Tau pathology in the brainstem mostly comprised a few neurofibrillary tangles and fell within the range of age-related changes. We found phosphorylated transactivation response element DNA-binding protein 43 kDa (pTDP-43) positive structures in five cases. Four of the five cases were observed in the substantia nigra (SN) but not limbic regions. The distribution pattern of pTDP-43 clearly differed from that in LB disease and older adults, suggesting that nigral degeneration is the primary lesion in the Sagamihara family. TDP-43 pathology in the Sagamihara family was different from those observed in TDP-43 proteinopathy that causes parkinsonism, which could be a secondary change; however, it may influence the course of the disease. Degeneration of the SN with relative preservation of the LC is a consistent finding in Sagamihara families, with or without LBs. These findings suggest that members of the Sagamihara family harbor a synuclein-independent neurodegenerative pathway and exhibit differential vulnerabilities depending on the brain region.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"450"},"PeriodicalIF":4.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248355","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}