Journal of Neurology最新文献

{"title":"Clonidine for the management of crises in stiff-person syndrome.","authors":"Salvatore Maria Lima, Nicasio Rini, Andrea Calì, Filippo Brighina, Vincenzo Di Stefano","doi":"10.1007/s00415-025-13226-6","DOIUrl":"10.1007/s00415-025-13226-6","url":null,"abstract":"<p><p>Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by high titers of antibodies against glutamic acid decarboxylase (GAD) and impaired GABAergic inhibitory neurotransmission. If not promptly treated, SPS progresses to disability with high risk of respiratory insufficiency; therefore, it is essential to apply the best therapeutic regimens since the beginning, both in the chronic and in the emergency setting during exacerbations. To date, there are no defined guidelines for the treatment of this rare disease. In this study, we report the case of a woman affected by refractory SPS who benefited from clonidine with immediate resolution of stiffness and SPS crisis.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"485"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540576","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":"Comparative efficacy and safety of irreversible (rasagiline) and reversible (safinamide) monoamine oxidase inhibitors as add-on therapy for Parkinson's disease.","authors":"Marwah Bintay Khalid, Faizan Shahzad, Momina Riaz Siddiqui, Muhammad Zain Ul Abedin, Saad Hulou, Besher Shami, Syed Ijlal Ahmed","doi":"10.1007/s00415-025-13230-w","DOIUrl":"10.1007/s00415-025-13230-w","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a progressive, neurodegenerative condition caused by progressive loss of dopaminergic neurons of the substantia nigra. Safinamide and rasagiline are both novel medications that are indicated for PD. Safinamide (reversible) and rasagiline (Irreversible) are selective monoamine oxidase B inhibitors which work by decreasing the degradation of dopamine in the brain.</p><p><strong>Objective: </strong>This network meta-analysis aimed to examine the efficacy and safety of both drugs as add-on therapy in patients with Parkinson's disease.</p><p><strong>Methodology: </strong>A systematic literature search of PubMed, Embase, and Cochrane databases was conducted in September 2024. Primary outcomes were Changes in the Unified Parkinson's Disease Rating Scale (UPDRS-III) and adverse effects. Standardized mean difference (SMD) and odds ratio (OR) were calculated with 95% confidence intervals. Surface Under Cumulative Ranking Curve (SUCRA) was used to compare individual interventions. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess the risk of bias in studies.</p><p><strong>Results: </strong>The search query resulted in 557 studies. After screening, 15 studies were included in the final analysis, totaling 5676 participants. Safinamide (100 mg) was associated with the highest change in UPDRS-III scores (SMD = 0.3007, 95% CI = [0.1710-0.4304], z-score = 4.54, p value =  < 0.0001, I2 = 55.8%, SUCRA = 71.17%), with rasagiline (1 mg) being a close contender with a SUCRA of 70.64%. Safinamide (50 mg) had the lowest odds of serious adverse events (SAEs) with OR = 0.4394 (95% CI = [0.2231-0.8652], z-score = - 2.38, p value = 0.0174, I2 = 0%, SUCRA = 99.34%). Safinamide (100 mg) had the second-lowest odds of SAEs (OR = 0.9575, 95% CI = [0.6520-1.4061], z-score = - 0.22, p value = 0.8246, I2 = 0%, SUCRA = 66.96%). Almost all the studies had a low risk of bias.</p><p><strong>Conclusion: </strong>Safinamide (100 mg) has good efficacy outcomes, whereas safinamide (50 mg) has favorable safety outcomes as compared to rasagiline for add-on therapy for PD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"486"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540577","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":"Equity in neuromuscular research: a 20-year analysis of race, ethnicity, sex, and age representation.","authors":"Lorenzo Fontanelli, Gabriele Vadi, Gabriele Bellini, Andrea Cossu, Gabriele Siciliano","doi":"10.1007/s00415-025-13208-8","DOIUrl":"10.1007/s00415-025-13208-8","url":null,"abstract":"<p><strong>Objectives: </strong>We conducted a systematic analysis of studies on neuromuscular diseases registered on ClinicalTrials.gov over the last 20 years to assess disparities in study populations.</p><p><strong>Methods: </strong>Data from interventional and observational neuromuscular disease studies initiated between January 1, 2004, and December 31, 2024, were retrieved from ClinicalTrials.gov and PubMed/MEDLINE. Collected variables included participant race, ethnicity, sex, eligible age range, mean and median ages, as well as study funding source, start year, and phase. These variables were analyzed to evaluate disparities in race, ethnicity, and age across studies and over time.</p><p><strong>Results: </strong>A total of 2166 studies were screened, with 462 meeting inclusion criteria, encompassing data from 37,131 participants. Most participants were male (61.4%), White (83.5%), and non-Hispanic/Latino (87.6%). While the proportion of studies reporting race and ethnicity increased over time (p < 0.001 and p = 0.001, respectively), the racial and ethnic composition of participants remained unchanged (p = 1). Studies on X-linked recessive disorders (i.e., Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, and spinal and bulbar muscular atrophy (SMA)) predominantly excluded female participants. Regarding age accessibility, 37.9% of studies allowed children. Similarly, trial accessibility for older adults was limited. Even in studies with broader age eligibility, mean and median participant ages clustered around midlife, with underrepresentation at both age extremes. Notably, about half of DMD and SMA studies excluded participants over 16 and 18 years, respectively.</p><p><strong>Conclusion: </strong>Significant disparities persist in race, ethnicity, and age representation in neuromuscular disease clinical research, highlighting the need for more inclusive study designs.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"483"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528422","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":"Added value of spinal cord MRI in detecting active disease in non-relapsing progressive multiple sclerosis patients.","authors":"Marco Vercellino, S Marasciulo, C Bosa, A Rolando, P Garelli, M L Vassallo, V Gallina, G Morana, P Cavalla","doi":"10.1007/s00415-025-13217-7","DOIUrl":"10.1007/s00415-025-13217-7","url":null,"abstract":"<p><strong>Introduction: </strong>Spinal cord MRI is not routinely recommended in the monitoring of MS. In patients with progressive MS (pMS), presence of disease activity is an important predictor of treatment response to currently approved treatments. The aim of this study was to investigate the added usefulness of spinal cord MRI in the identification of active disease in patients with non-relapsing pMS.</p><p><strong>Methods: </strong>MRI records were reviewed in a cohort of pMS patients. All patients with at least 2 years of follow-up with the same MRI scanner were included in the study. Patients with clinical relapses during follow-up were excluded from the study. Asymptomatic combined unique active lesions (CUA) were defined as any new T2/STIR lesion or any T1 Gd + lesion, in absence of a clinical relapse.</p><p><strong>Results: </strong>185 non-relapsing pMS patients were included in the study (41 primary progressive, 144 secondary progressive; median EDSS 6.0), out of a cohort of 422 pMS patients. Mean length of MRI follow-up was 4.0 years (range 2-8). 28/185 (15.1%) patients showed new asymptomatic CUA brain lesions during follow-up, 14/185 (7.6%) patients showed new asymptomatic CUA spinal cord lesions, 4/185 (3.4%) patients showed new asymptomatic CUA lesions both in the brain and in the spinal cord. Overall, the addition of spinal cord MRI allowed to detect disease activity in + 43.75% more patients than brain MRI only.</p><p><strong>Conclusion: </strong>The addition of spinal cord MRI allows to detect active disease in a significantly higher proportion of non-relapsing pMS patients. This is important in stratifying expected response to treatment and to inform treatment choices.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"482"},"PeriodicalIF":4.8,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528421","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":"Long-term effectiveness and safety of ocrelizumab: a single-centre real-world study.","authors":"Tiziana Zaccone, Lucia Moiola, Simone Guerrieri, Agostino Nozzolillo, Chiara Zanetta, Irene Gattuso, Angela Genchi, Federica Esposito, Maria G Scarale, Paola M V Rancoita, Maria A Rocca, Massimo Filippi","doi":"10.1007/s00415-025-13224-8","DOIUrl":"10.1007/s00415-025-13224-8","url":null,"abstract":"<p><strong>Background: </strong>This retrospective single-centre study evaluated the effectiveness and safety of ocrelizumab (OCR) in relapse-onset multiple sclerosis (RMS) and primary progressive MS (PPMS) and identified predictors of treatment response.</p><p><strong>Methods: </strong>We included 260 RMS and 73 PPMS patients treated with ocrelizumab for ≥ 1 year at our MS Centre until May 2024.</p><p><strong>Results: </strong>Median follow-up was 3.90 years for RMS and 4.23 years for PPMS. Within 2 years from treatment initiation, annualized relapse rate (ARR) decreased from 0.412 to 0.014 and was maintained low throughout follow-up in RMS, with no relapses in PPMS. MRI activity significantly declined and was maintained in both groups (p < 0.0001). After 3 years, confirmed disability progression (CDP)-free survival was high in relapsing-remitting MS (> 97%) and lower in secondary progressive MS (48.9%) and PPMS (57.2%). Predictors of ocrelizumab inefficacy included higher baseline Expanded Disability Status Scale (EDSS), older age and longer disease duration in RMS; male sex, older age and prior lower-efficacy treatments in PPMS. Adverse events were in line with previous clinical studies, with hypogammaglobulinemia and recurrent infections being the most frequent.</p><p><strong>Conclusions: </strong>In this study we confirm ocrelizumab sustained efficacy in controlling inflammatory disease activity, with greater impact in RMS, with a favourable safety profile. Early treatment initiation is crucial to prevent irreversible disability accumulation.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"481"},"PeriodicalIF":4.8,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528423","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":"Mitochondrial pathology in inflammatory myopathies: a marker of worse clinical outcome.","authors":"Antonio Lauletta, Luca Bosco, Gioia Merlonghi, Yuri Matteo Falzone, Marta Cheli, Roberta Piera Bencivenga, Dario Zoppi, Marco Ceccanti, Felix Kleefeld, Sarah Léonard-Louis, Werner Stenzel, Olivier Benveniste, Lorenzo Maggi, Stefano Carlo Previtali, Matteo Garibaldi","doi":"10.1007/s00415-025-13192-z","DOIUrl":"10.1007/s00415-025-13192-z","url":null,"abstract":"<p><strong>Objectives: </strong>Mitochondrial dysfunction is well documented in inclusion body myositis (IBM), but its role in non-IBM myositis remains unclear. This study aimed to investigate the prevalence and clinical significance of mitochondrial pathology in non-IBM myositis and to assess its potential role as a marker for disease progression towards IBM, treatment response, and clinical outcomes.</p><p><strong>Methods: </strong>Muscle biopsies from 850 patients with inflammatory myopathy (IM) across 6 neuromuscular centers in Italy, France, and Germany were retrospectively analyzed. Inclusion required meeting diagnostic criteria for definite adult IM, mitochondrial pathology (age-exceeding numbers of COX-negative fibers), and exclusion of definite IBM according to Hilton-Jones 2013 criteria. The percentage of COX-negative fibers was quantified, correlated with clinical outcomes, and compared with myositis control cases without relevant signs of mitochondrial alterations.</p><p><strong>Results: </strong>Twenty-five patients with non-IBM myositis and mitochondrial abnormalities were identified. These patients, predominantly women (68%), had a mean onset age of 58.8 years. Polymyositis with mitochondrial pathology (PM-Mito) and nonspecific myositis (NSM) were the most prevalent subtypes (72%). The mean percentage of COX-negative fibers was 3% (0.25-8.5%) in these patients. The presence of mitochondrial pathology was associated with treatment refractoriness and worse clinical outcome evaluated based on residual muscle weakness and the level of independence (p < 0.005). A higher percentage of COX-negative fibers also correlated with poorer clinical outcomes (p = 0.031). Four patients, initially diagnosed with PM-Mito and NSM, progressed to definite IBM.</p><p><strong>Conclusions: </strong>Mitochondrial dysfunction represents a key element informing about disease severity and poor clinical outcomes in non-IBM myositis. It may predict progression to IBM, especially in PM-Mito and NSM, and guide treatment strategies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"480"},"PeriodicalIF":4.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497340","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":"William Halse Rivers Rivers (1864-1922).","authors":"Andrew J Larner","doi":"10.1007/s00415-025-13212-y","DOIUrl":"10.1007/s00415-025-13212-y","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"479"},"PeriodicalIF":4.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484747","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":"Joseph Arderne Ormerod (1848-1925).","authors":"Andrew J Larner","doi":"10.1007/s00415-025-13211-z","DOIUrl":"10.1007/s00415-025-13211-z","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"477"},"PeriodicalIF":4.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484745","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":"Regional free-water diffusion is more strongly related to neuroinflammation than neurodegeneration.","authors":"Vishaal Sumra, Mohsen Hadian, Allison A Dilliott, Sali M K Farhan, Andrew R Frank, Anthony E Lang, Angela C Roberts, Angela Troyer, Stephen R Arnott, Connie Marras, David F Tang-Wai, Elizabeth Finger, Ekaterina Rogaeva, Joseph B Orange, Joel Ramirez, Lorne Zinman, Malcolm Binns, Michael Borrie, Morris Freedman, Miracle Ozzoude, Robert Bartha, Richard H Swartz, David Munoz, Mario Masellis, Sandra E Black, Roger A Dixon, Dar Dowlatshahi, David Grimes, Ayman Hassan, Robert A Hegele, Sanjeev Kumar, Stephen Pasternak, Bruce Pollock, Tarek Rajji, Demetrios Sahlas, Gustavo Saposnik, Maria Carmela Tartaglia","doi":"10.1007/s00415-025-13201-1","DOIUrl":"10.1007/s00415-025-13201-1","url":null,"abstract":"<p><strong>Introduction: </strong>Recent research has suggested that neuroinflammation may be important in the pathogenesis of neurodegenerative diseases. Free-water diffusion (FWD) has been proposed as a non-invasive neuroimaging-based biomarker for neuroinflammation.</p><p><strong>Methods: </strong>Free-water maps were generated using diffusion MRI data in 367 patients from the Ontario Neurodegenerative Disease Research Initiative (108 Alzheimer's Disease/Mild Cognitive Impairment, 42 Frontotemporal Dementia, 37 Amyotrophic Lateral Sclerosis, 123 Parkinson's Disease, and 58 vascular disease-related Cognitive Impairment). The ability of FWD to predict neuroinflammation and neurodegeneration from biofluids was estimated using plasma glial fibrillary-associated protein (GFAP) and neurofilament light chain (NfL), respectively.</p><p><strong>Results: </strong>Recursive Feature Elimination (RFE) performed the strongest out of all feature selection algorithms used and revealed regional specificity for areas that are the most important features for predicting GFAP over NfL concentration. Deep learning models using selected features and demographic information revealed better prediction of GFAP over NfL.</p><p><strong>Discussion: </strong>Based on feature selection and deep learning methods, FWD was found to be more strongly related to GFAP concentration (measure of astrogliosis) over NfL (measure of neuro-axonal damage), across neurodegenerative disease groups, in terms of predictive performance. Non-invasive markers of neurodegeneration such as MRI structural imaging that can reveal neurodegeneration already exist, while non-invasive markers of neuroinflammation are not available. Our results support the use of FWD as a non-invasive neuroimaging-based biomarker for neuroinflammation.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"478"},"PeriodicalIF":4.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484746","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":"Quantitative cervical cord MRI in spinal muscular atrophy: a sensitive imaging biomarker of disease evolution and treatment.","authors":"C Asteggiano, L Mazzocchi, L Farina, M Paoletti, L Barzaghi, E Caverzasi, S Parravicini, M I Dainesi, A Gardani, G Savini, N Bergsland, E Ballante, C A M Gandini Wheeler-Kingshott, A Berardinelli, A Pichiecchio","doi":"10.1007/s00415-025-13205-x","DOIUrl":"10.1007/s00415-025-13205-x","url":null,"abstract":"<p><strong>Background: </strong>Nusinersen is an approved disease-modifying therapy for spinal muscular atrophy (SMA), a rare neuromuscular disease characterized by degeneration of alpha motor neurons in the brainstem and spinal cord (SC), leading to progressive muscle atrophy and weakness. This exploratory study investigated the potential of quantitative SC magnetic resonance imaging (MRI) as a biomarker for monitoring treatment-related changes in pediatric and adult SMA patients treated with nusinersen at different disease stages.</p><p><strong>Methods: </strong>Five pediatric and three adult SMA patients underwent clinical assessments, including the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM), along with SC MRI at multiple time points (TPs) during nusinersen treatment. At each TP, total cross-sectional area (TCA), grey matter area (GM_area), and magnetization transfer saturation (MT_sat) were measured at multiple cervical SC levels.</p><p><strong>Results: </strong>All pediatric patients showed a progressive increase in SC TCA and GM_area over time, paralleled by improvements in HFMSE and RULM scores. In contrast, adult patients exhibited stable SC MRI measures with modest functional gains. MT_sat values remained largely stable across time points, with a mild decrease observed at TP5. TCA and GM_area showed positive association trends with clinical scales.</p><p><strong>Conclusion: </strong>Nusinersen showed beneficial effects in both adult and pediatric SMA patients, with more marked improvements in children. Quantitative SC MRI metrics, especially TCA and GM_area, reflected clinical trends and may serve as non-invasive biomarkers for monitoring treatment effects, pending validation in larger cohorts.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"475"},"PeriodicalIF":4.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475685","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}