Journal of Neurology最新文献

{"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}

{"title":"Monitoring anti-Rituximab antibodies in myasthenia gravis affects the time to event during Rituximab treatment.","authors":"Charlotte Héraud, Saskia Bresch, Véronique Bourg, Cassandre Landes-Château, Caroline Ruetsch-Chelli, Michel Ticchioni, Barbara Seitz-Polski, Christine Lebrun-Frenay","doi":"10.1007/s00415-025-13161-6","DOIUrl":"10.1007/s00415-025-13161-6","url":null,"abstract":"<p><strong>Introduction: </strong>Rituximab (RTX) effectively manages myasthenia gravis (MG) by reducing relapse rates. Anti-Rituximab antibodies can develop in autoimmune diseases and may lead to RTX resistance. Although RTX infusions are increased, these antibodies do not influence the occurrence of adverse events. We conducted a retrospective study to evaluate how anti-drug antibodies (ADAs) impact treatment efficacy.</p><p><strong>Methods: </strong>We reviewed 101 MG patients treated with first- or second-line RTX at Nice University Hospital from 2016 to 2023. Clinical assessments were performed quarterly using the Osserman Score (OS). Biological tests included ADA levels, RTX serum levels, CD19+CD27+ memory B cells, and CD19+ cell counts.</p><p><strong>Results: </strong>Among 101 patients, 38 developed ADAs (37.6%), with a median onset of 433.5 days after the first infusion. The ADA group had significantly more RTX infusions (6.18 vs. 4.29, p=0.002) and more prolonged treatment durations (1908.26 vs. 1441.3 days, p=0.006). No differences in age, gender, or prior immunosuppression were noted. OS scores revealed no significant difference between ADA-positive and ADA-negative patients. The interval between infusions remained consistent before and after the appearance of ADAs.</p><p><strong>Discussion: </strong>ADAs were found in one-third of MG patients treated with RTX, a higher prevalence than in other conditions. The number of RTX infusions was significantly greater in the ADA-positive group, and the longer is the treatment duration, the higher the likelihood of developing ADAs. Our findings suggest a need to reconsider routine ADA testing, as it does not correlate with clinical outcomes or infusion intervals. This raises questions about how to tailor maintenance therapy for MG patients stabilized with RTX.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"451"},"PeriodicalIF":4.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248354","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":"Effectiveness of perampanel as only concomitant antiseizure medication for highly active epilepsy: insight from a real-world, multicenter retrospective study.","authors":"Angelo Pascarella, Marilisa Pasquale, Domenico Abelardo, Sara Gasparini, Oreste Marsico, Roberta Cutellè, Vittoria Cianci, Alfonso Iudice, Francesca Bisulli, Paolo Bonanni, Emanuele Caggia, Alfredo D'Aniello, Carlo Di Bonaventura, Jacopo C DiFrancesco, Elisabetta Domina, Fedele Dono, Antonio Gambardella, Carla Marini, Alfonso Marrelli, Sara Matricardi, Alessandra Morano, Francesco Paladin, Rosaria Renna, Marta Piccioli, Pasquale Striano, Michele Ascoli, Angela La Neve, Emilio Le Piane, Alessandro Orsini, Claudia Torino, Simone Beretta, Umberto Aguglia, Edoardo Ferlazzo","doi":"10.1007/s00415-025-13184-z","DOIUrl":"10.1007/s00415-025-13184-z","url":null,"abstract":"<p><strong>Introduction: </strong>Managing patients with highly frequent seizures poses significant challenges for clinicians due to their high resistance to therapy. This study aims to evaluate the 12-month efficacy, safety, and tolerability of PER as the sole add-on therapy for patients with highly active epilepsy in a real-world setting.</p><p><strong>Methods: </strong>Data from the previous Italian retrospective, observational, multicenter \"PERampanel as Only Concomitant Antiseizure Medication\" (PEROC) study were analyzed, categorizing patients by baseline seizure frequency into three groups: < 5, 5-20, and > 20 seizures/month. Retention, responder (≥ 50% seizure reduction) rates, seizure-free rates and adverse events (AEs) were analyzed. Sub-analyses examined early (≤ 1 previous ASM) vs. late (> 2 previous ASMs) add-on groups.</p><p><strong>Results: </strong>The sample included 485 patients with focal and generalized epilepsy: 354 with < 5 seizures/month, 79 with 5-20, and 52 with > 20 seizures/month. Retention rates at 12 months were 75.1%, 68%, and 58.1.7%, respectively. Perampanel significantly reduced seizure frequency in all groups, with responder rates of 71.2%, 61.8%, and 63.2% at the 12-month follow-up. Patients with more frequent seizures (> 20 and 5-20 seizures/month) had lower seizure-free rates (15.8% and 23.5%) compared to those with < 5 seizures/month (49.5%, p = 0.001). AEs, mainly dizziness and irritability occurred in 30% of patients, without significant differences between groups (p = 0.092).</p><p><strong>Conclusions: </strong>PER, as the sole adjunctive therapy, demonstrated good effectiveness and tolerability in a real-world setting, even for patients with highly active epilepsy. These findings suggest PER as a valuable early treatment option to improve seizure control and quality of life in this challenging population.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"449"},"PeriodicalIF":4.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248353","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":"Characterisation of a large, single-centre cohort of patients with Becker muscular dystrophy to inform standardised care guidelines.","authors":"Pietro Riguzzi, Holly Borland, Meredith K James, John Bourke, Chiara Marini Bettolo, Robert Muni Lofra, Jordi Diaz-Manera, Giorgio Tasca, Marianela Schiava, Maha ElSeed, Elizabeth Harris, Emma Grover, Chloe Geagan, Carla Bolano Diaz, Ariele Barreto Haagsma, Doaa Salman, Tara Reeves, Goknur S Kocak, Emma Robinson, Peter Waldock, Michelle McCallum, Jassi Michell-Sodhi, Dionne Moat, Karen Wong, Ana Topf, Elena Pegoraro, Luca Bello, Volker Straub, Michela Guglieri","doi":"10.1007/s00415-025-13126-9","DOIUrl":"10.1007/s00415-025-13126-9","url":null,"abstract":"<p><strong>Aims: </strong>This retrospective, cross-sectional study aimed to characterise a large cohort of paediatric and adult patients with Becker muscular dystrophy (BMD) to inform clinical care.</p><p><strong>Results: </strong>The analysis included data from 163 male patients with genetically confirmed BMD followed up at a highly specialised neuromuscular centre between 1982 and 2023. The mean age at last neuromuscular assessment was 33.2 years (range 1.4-86.3). Large deletions in the DMD gene were the most common variants (78% of cases), followed by large duplications and small variants, each accounting for 11% of cases. BMD diagnosis was prompted by skeletal muscle symptoms in 52.2% of cases, a positive family history in 27.6%, neuropsychiatric issues or diagnoses in 9.7%, incidental findings in 6.7%, and cardiomyopathy in 3.8%. Twenty-three percent of patients were non-ambulant at last evaluation, with a mean age at loss of ambulation (LoA) of 42.2 years (range 11.2-77.6 years). Disease duration correlated with the severity of motor impairment (expressed as fully ambulant, ambulant with limitation, ambulant with aids, non-ambulant) at last assessment. Cardiac involvement was observed in 52.3% of patients. Severe respiratory impairment was rare and more prevalent in non-ambulant patients. Neuropsychiatric issues were common (44.2%), but only 18.4% of patients had a formal diagnosis.</p><p><strong>Conclusions: </strong>Retrospective analyses of clinical case records contribute to improved understanding of the variability of phenotypes of BMD. Combined with data from other large cohorts, these findings can contribute to the development of standard of care guidelines for BMD and inform the design of clinical trials of novel therapies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"448"},"PeriodicalIF":4.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248352","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":"Serological analysis of gluten-related antibodies in idiopathic neuropathies and cerebellar ataxia.","authors":"Maxine D Rouvroye, Janna Warendorf, Alexander Vrancken, Filip Eftimov, Luuk Wieske, Catharina G Faber, Janneke G J Hoeijmakers, Jan Damoiseaux, Bart van de Warrenburg, Judith van Gaalen, Renate van der Molen, Gerd Bouma, Hetty Bontkes","doi":"10.1007/s00415-025-13187-w","DOIUrl":"10.1007/s00415-025-13187-w","url":null,"abstract":"<p><p>Immune reactivity to gluten in the development of peripheral neuropathies and cerebellar ataxia has been suggested for decades, but evidence is scarce. The aim of the current study was to test the prevalence of tissue transglutaminase 2 (anti-TG2), tissue transglutaminase 6 (anti-TG6), and gliadin antibodies (anti-gliadin) in a large cross-sectional study. The sera of patients with idiopathic cerebellar ataxia, idiopathic small fibre neuropathy (SFN) and chronic idiopathic axonal polyneuropathy (CIAP), and controls with a comparable age distribution and men/women ratio were collected. The sera were analysed for anti-gliadin IgA/IgG (manufacturer's and lower cut-off), anti-TG2 IgA and anti-TG6 IgA/IgG. In total, 683 samples were analysed: 476 patients (249 SFN, 161 CIAP and 66 idiopathic cerebellar ataxia) and 195 controls. There were no differences between disease and control group in the prevalence of elevated anti-TG6, anti-TG2 and anti-gliadin using the manufacturer's cut-off. Using a lower cut-off of 3 U/mL, previously used by others for gluten-related neurological disorders, anti-gliadin IgA was positive in 20.8% patients vs 12.8% controls (p = 0.017) and anti-gliadin IgG in 7.6% vs 2.6% (p = 0.013), respectively. In subgroup analyses, significant differences were only observed in SFN for anti-gliadin IgA and in idiopathic cerebellar ataxia for anti-gliadin IgG using this lower cut-off after adjusting for sex and age. In conclusion, no difference in anti-TG2, anti-TG6 and anti-gliadin levels were observed between patients and controls. Only when using the lower cut-off (3 U/mL), the patients with SFN and idiopathic cerebellar ataxia were more often positive for anti-gliadin than controls. Whether these low-titre antibodies are gluten related, have any pathophysiological relevance, or reflect an epiphenomenon of neurodegeneration or gut inflammation is unknown.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"447"},"PeriodicalIF":4.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248357","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":"Potential use of the SARS-CoV-2 monoclonal antibody sipavibart in people with multiple sclerosis: definition of different patient archetypes from an Italian expert group perspective.","authors":"Chiara Zanetta, Claudio Gasperini, Maria Pia Amato, Diego Centonze, Paolo Gallo, Francesco Patti, Agostino Riva, Massimo Filippi","doi":"10.1007/s00415-025-13188-9","DOIUrl":"10.1007/s00415-025-13188-9","url":null,"abstract":"<p><strong>Introduction: </strong>Immunocompromised people, including people with MS (PwMS) remain at increased risk of severe COVID-19 outcomes, highlighting how this population needs additional preventive measures beyond current vaccination. Seven neurologists with experience in the MS field and one infectivologist discussed the use of COVID-19 pre-exposure prophylaxis (PrEP) in PwMS, identifying patients' archetypes for PrEP with the monoclonal antibody sipavibart.</p><p><strong>Methods: </strong>The following topics were discussed: description of the current SARS-CoV-2 infection scenario; identification of the characteristics of the fragile patient; identification of the ideal candidate for PrEP with sipavibart. The recommendations were then produced accordingly.</p><p><strong>Results: </strong>Vaccination remains a crucial preventive measure for COVID-19. Age, male sex, and comorbidities are associated with severe outcomes among patients with MS. MS-specific risk factors include higher disability, a progressive disease course, a recent administration of steroids and the treatment with anti-CD20 agents, S1P receptor modulators, cladribine, and anti-CD52 antibodies. Pediatric patients and subjects with neuromyelitis optica spectrum disorder should also be considered fragile subjects. Subjects who could benefit from PrEP include: PwMS who present risk factors similar to the general population or who present disease-specific risk factors, non-vaccinated PwMS, and PwMS under S1P receptor modulators, anti-CD20 agents, alemtuzumab or cladribine and who present at least one risk factor similar to the general population or one disease-specific risk factor.</p><p><strong>Discussion: </strong>Subjects with general or disease specific risk factors for severe infections, patients treated with S1P receptor modulators, anti-CD20 agents, alemtuzumab or cladribine, pediatric patients, and pregnant women with MS could represent the ideal candidates for PrEP with sipavibart.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"446"},"PeriodicalIF":4.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248356","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":"A disproportionality analysis of nervous system adverse events associated with disease-modifying therapies in multiple sclerosis: insights from the FDA adverse event reporting system (FAERS).","authors":"Hui Chen","doi":"10.1007/s00415-025-13189-8","DOIUrl":"10.1007/s00415-025-13189-8","url":null,"abstract":"<p><strong>Background: </strong>Disease-modifying therapies (DMTs) have significantly improved the management of multiple sclerosis (MS), but their potential nervous system adverse events (AEs) remain a critical concern. This study aims to evaluate the risk of nervous system AEs associated with 11 DMTs using the FDA Adverse Event Reporting System (FAERS) database, following the READUS-PV guidelines.</p><p><strong>Methods: </strong>We performed a disproportionality analysis on FAERS data from Q1 2004 to Q3 2024, focusing on nervous system AEs related to DMTs, such as Alemtuzumab (AL), Ofatumumab (OF), Ocrelizumab (OC), and Fingolimod (FI). Using disproportionality analysis and Bayesian methods, we identified signals of these AEs. We also conducted subgroup analyses across age, gender, weight, geographic regions, and outcomes to assess AE distribution. In addition, a sensitivity analysis was done to evaluate the consistency of the association between DMTs and nervous system AEs across severities. The time to onset and clinical characteristics of AEs were examined as well.</p><p><strong>Results: </strong>Among 245,469 nervous system AE reports, Siponimod (SI), Natalizumab (NA), FI, and Teriflunomide (TE) exhibited the highest signal values (ROR > 3.0), with SI showing the strongest association [ROR = 3.44, 95% CI (3.34-3.55)]. Females accounted for 76.0% of nervous system AEs, and severe AEs such as central nervous system lesions (mortality rate: 0.97%) and cognitive disorders (mortality rate: 0.94%) were detected. The median time to onset of AEs varied significantly across DMTs, ranging from 14 days for AL to 816 days for Interferon Beta-1a (IN). Subgroup analyses highlighted variations in AE reporting across different demographics and geographic regions. The sensitivity analysis further confirmed the robustness of our findings, indicating consistent associations between DMTs and severe nervous system AEs.</p><p><strong>Conclusions: </strong>This study highlights significant differences in the nervous system AEs profiles of DMTs, with SI, NA, FI, and TE showing higher risks of nervous system AEs. These findings underscore the importance of vigilant monitoring and personalized treatment strategies to mitigate nervous system risks in MS patients. Further research is needed to confirm these associations and investigate the mechanisms that underlie them.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"445"},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216147","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":"Correction: In multiple sclerosis patients a single serum neurofilament light chain (sNFL) dosage is strongly associated with 12 months outcome: data from a real-life clinical setting.","authors":"Simona Malucchi, Cecilia Irene Bava, Paola Valentino, Serena Martire, Marianna Lo Re, Antonio Bertolotto, Alessia Di Sapio","doi":"10.1007/s00415-025-13107-y","DOIUrl":"10.1007/s00415-025-13107-y","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"444"},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216149","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":"Structural brain changes contributing to motor signs in pure hereditary spastic paraplegia type 4.","authors":"Claudia Piervincenzi, Francesco Asci, Emma Gangemi, Antonio Funcis, Alessandro Zampogna, Marco Falletti, Gabriella Silvestri, Salvatore Rossi, Gianmarco Dalla Zanna, Claudia Celletti, Filippo Camerota, Costanza Giannì, Nikolaos Petsas, Loredana Maggi, Patrizia Pantano, Antonio Suppa","doi":"10.1007/s00415-025-13155-4","DOIUrl":"10.1007/s00415-025-13155-4","url":null,"abstract":"<p><strong>Background/objectives: </strong>Spastic paraplegia type 4 (SPG4; also known as SPAST-HSP), the most prevalent variant among pure Hereditary Spastic Paraplegias (HSPs), is clinically characterized by progressive spasticity and weakness in the lower limbs. The present neuroimaging study specifically investigated possible changes in the corticospinal (CST) and thalamo-cortical tracts (TCT) structural integrity and broader cortical, subcortical and spinal pathways, topographically related to upper and lower limbs in SPG4.</p><p><strong>Methods: </strong>Forty patients with SPG4 and 40 age- and sex-matched healthy controls underwent 3 T MRI scanning. MRI analyses included: (1) global and primary motor areas cortical thickness; (2) cortical, basal ganglia, thalamic and cerebellar volumetry; (3) diffusion-based probabilistic tractography of CST and TCT serving the arms and legs; and (4) spinal cord area.</p><p><strong>Results: </strong>SPG4 patients showed significant reductions in thalamic volumes as well as spinal cord area when compared with controls. The volume reduction in thalamic regions correlated with disease severity and spasticity-related impairments. Structural changes in CST and TCT tracts in SPG4 patients were prominent in bundles topographically related to the lower limbs compared with the upper limbs.</p><p><strong>Conclusions: </strong>Our findings point to significant thalamic atrophy as well as white matter tract degeneration topographically related to the lower limbs in SPG4 patients. The findings overall suggest new potential markers for disease progression and functional decline in SPG4 patients.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"440"},"PeriodicalIF":4.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208778","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}