Neurology and Therapy最新文献

{"title":"Update on Parkinson's Disease Psychosis: Epidemiology, Mechanisms and Management.","authors":"Caroline Kruse, Daniel Weintraub, John Duda, James F Morley","doi":"10.1007/s40120-026-01014-x","DOIUrl":"https://doi.org/10.1007/s40120-026-01014-x","url":null,"abstract":"<p><p>Psychosis in Parkinson's disease (PD) is a common and debilitating non-motor symptom that can occur at any stage of the disease. PD psychosis (PDP) manifests as a diverse clinical spectrum that can include misperceptions, passage and presence phenomena, hallucinations, and delusions, alone or in combination. This review explores the epidemiology and underlying neurobiological mechanisms of psychosis in PD, describes the symptom spectrum experienced by patients, and reviews the evidence supporting current and future therapies for psychosis in PD. Pimavanserin and clozapine are the only pharmacologic therapies for PDP that have been found to be efficacious in randomized controlled trials, though quetiapine is most frequently used despite lacking positive trial results. Future research that continues to clarify the exact pathophysiology of psychosis in PD will improve the current therapeutic approaches, and ongoing randomized clinical trials of these therapies are necessary to identify the safest and most efficacious treatments for PD patients with psychosis.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Rimegepant for the Acute Treatment of Migraine Among Participants Using Different Types of Preventive Therapy: Analyses from CONFIDENCE.","authors":"Richard B Lipton, Peter J Goadsby, Patricia Pozo-Rosich, Alexandre Urani, Giorgio Lambru, Todd J Schwedt, Kristina M Fanning, Ryan C Bostic, Feng Dai, Lucy Abraham, Karin Hygge Blakeman","doi":"10.1007/s40120-026-01024-9","DOIUrl":"https://doi.org/10.1007/s40120-026-01024-9","url":null,"abstract":"<p><strong>Introduction: </strong>This analysis assessed the real-world effectiveness of rimegepant for the acute treatment of migraine in patients taking different types of preventive medication.</p><p><strong>Methods: </strong>The prospective, observational, CONFIDENCE study recruited participants in the United States with 3-14 headache days/30 days and a rimegepant prescription for the acute treatment of migraine via the Migraine Buddy^® app. Over a 28-day period, participants reported daily on the occurrence, treatment, and outcomes of migraine attacks. The proportion of rimegepant-treated attacks that achieved meaningful pain relief, meaningful improvement in function, or treatment satisfaction were calculated by preventive medication type [none; oral preventive medication (OPM) only; onabotulinumtoxinA (onaBoNT-A) with/without OPM; or calcitonin gene-related peptide monoclonal antibody (CGRP mAb) with/without OPM]. Pain and functional outcomes were compared between attacks treated with rimegepant versus other acute medication combinations using adjusted generalized linear mixed models with logit link and random intercept for each participant.</p><p><strong>Results: </strong>Among 2169 rimegepant-treated attacks, meaningful pain relief was achieved at 2 h and 4 h in 61.3% and 81.8%, respectively; corresponding values for meaningful improvement in function were 57.6% and 78.5%. Odds for all outcomes were higher with rimegepant versus other acute medication treatment combinations. Satisfaction with rimegepant treatment of the attack was > 60% across domains related to speed and effectiveness. Rates and adjusted odds ratios [aORs (95% CI)] for meaningful pain relief within 2 h with rimegepant versus other acute medication treatment combinations were: all attacks 61.3% versus 49.6%, aOR = 1.93 (1.52, 2.45), P < 0.001; no preventive medication 70.0% versus 41.8%, aOR = 4.56 (2.09, 9.92), P < 0.001; OPM 64.7% versus 56.5%, aOR = 1.76 (1.06, 2.90), P < 0.05; onaBoNT-A 62.0% versus 49.5%, aOR = 1.89 (1.24, 2.87), P < 0.01; and CGRP mAb 54.4% versus 46.8%, aOR = 1.66 (1.09, 2.53), P < 0.05.</p><p><strong>Conclusion: </strong>High rates of meaningful pain relief, meaningful improvement in function, and treatment satisfaction were observed with rimegepant for the acute treatment of migraine when used alongside different types of preventive medication in the real world.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT06467370. Graphical abstract available for this article.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cenobamate Improves Emotional Dysregulation, Impulsivity, and Apathy in Drug-Resistant Focal Epilepsy: A Longitudinal Neuropsychological Study.","authors":"Ilaria Sammarra, Adriana Saraceno, Iolanda Martino, Alessia Vono, Francesca Felicia Operto, Francesco Fortunato, Antonio Gambardella","doi":"10.1007/s40120-026-01022-x","DOIUrl":"https://doi.org/10.1007/s40120-026-01022-x","url":null,"abstract":"<p><strong>Introduction: </strong>Although effects on cognitive function have been reported during cenobamate (CNB) treatment, far less is known about how it may affect neuropsychological domains such as apathy, emotion dysregulation, and impulsivity. This prospective longitudinal study aims to assess psychopathological and cognitive changes after CNB introduction in adults with drug-resistant focal epilepsy, accounting for seizure outcome and burden of concomitant anti-seizure medication (ASM).</p><p><strong>Methods: </strong>We consecutively recruited adults with drug-resistant focal epilepsy who had undergone a comprehensive neuropsychological evaluation at baseline, before starting CNB, and at follow-up, 12 months after treatment introduction. The psychopathological battery included Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory, Difficulties in Emotion Regulation Scale (DERS-36), Barratt Impulsiveness Scale (BIS-11), Apathy Evaluation Scale (AES), and Quality of Life in Epilepsy Inventory (QoLIE-31). The cognitive assessment comprised Rey Auditory Verbal Learning Test (RAVLT), Digit-Span, Rey-Osterrieth Complex Figure Test, WEIGL, FAS, Stroop Color and Word Test, and Symbol Digit Modalities Test (SDMT). We applied linear mixed-effects models adjusted for responder status and total concomitant ASM defined daily dose (DDD) ratio.</p><p><strong>Results: </strong>Our cohort included 27 individuals (16 female; mean age 42.4 ± 16.7 years) showing a 74% responder rate with 30% achieved seizure freedom at follow-up. CNB treatment was associated with favorable changes in BDI-II (q = 0.009), DERS-36 (q = 2.36 × 10^-5), BIS-11 (q = 6.30 × 10^-8), AES (q = 4.87 × 10^-5), and QoLIE-31 (q = 0.009). RAVLT-Immediate performance likewise improved (q = 0.004), whereas SDMT worsened over time (q = 0.002); the remaining domains were unchanged. These effects remained significant after adjustment for responder status and total concomitant ASM DDD ratio: BDI-II [β (95% CI) = - 0.582 (- 0.943, - 0.221)], DERS-36 [β (95% CI) = - 0.550 (- 0.739, - 0.361)], BIS-11 [β (95% CI) = - 0.932 (- 1.144, - 0.719)], AES [β (95% CI) = - 1.001 (- 1.330, - 0.673)], QoLIE-31 [β (95% CI) = 0.488 (0.185, 0.791)], RAVLT-Immediate performance [β (95% CI) = 0.446 (0.255, 0.636)], and SDMT [β (95% CI) = - 0.294 (- 0.425, - 0.163)].</p><p><strong>Conclusion: </strong>Adjunctive CNB was correlated with psychopathological improvements alongside domain-specific cognitive changes, independent of seizure outcome and concomitant ASM burden. These findings further expand current knowledge on CNB impact and tolerability profile.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Qualitative Study of Lived Treatment Experiences and Preferences of Long-Term DMT Users with Relapsing-Remitting Multiple Sclerosis.","authors":"Clair-Antoine Veyrier, Patrick Vermersch, Olivier Casez, Olivier Heinzlef, Marianne Payet, Laura Luciani, Nicolas Collongues, Martin Duracinsky","doi":"10.1007/s40120-026-00959-3","DOIUrl":"10.1007/s40120-026-00959-3","url":null,"abstract":"<p><strong>Introduction: </strong>Relapsing-remitting multiple sclerosis (RRMS) requires prolonged use of disease-modifying therapies (DMTs), often perceived as burdensome. This study explored the lived treatment experiences of long-term DMT users with RRMS.</p><p><strong>Methods: </strong>This qualitative, non-interventional study used semi-structured interviews with 20 French-speaking adults with RRMS treated with DMTs for ≥ 10 years. Participants were recruited in France via patient associations and neurology clinics. Exclusion criteria included progressive MS or cognitive impairment. Interviews were conducted remotely and transcribed for thematic analysis using NVivo software, guided by a general inductive and grounded theory framework. Data saturation was monitored, and coding was performed by multiple researchers to ensure reliability.</p><p><strong>Results: </strong>Participants (mean age 52 years; 60% female; mean disease duration 20 years) reported strong preference for oral or infrequent infusion DMTs due to lower perceived treatment burden. Frequent home injections were linked with anxiety and reduced autonomy. Voluntary treatment pauses were common, motivated by fatigue or social needs, but constrained by the fear of relapse. Treatment experiences influenced identity and required substantial daily organization.</p><p><strong>Conclusion: </strong>Long-term patients with RRMS incorporate DMTs into their routines and identities, favoring less frequent, lower-burden regimens. Findings support the need for personalized care strategies that consider treatment fatigue and promote shared decision-making.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1917-1929"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Childhood Outdoor Exposure Raises Pediatric Multiple Sclerosis (PedMS) Risk.","authors":"Silvy Pilotto, Angelo Ghezzi, Stefania Maria Bova, Marzia Fronza, Pietro Annovazzi, Marta Simone, Antonio Gallo, Agnese Suppiej, Roberta Lanzillo, Sarah Rasia, Angela Berardinelli, Valentina Torri Clerici, Lucia Moiola, Maurizio Viri, Stefano Sotgiu, Simona Malucchi, Alessandra Protti, Carlotta Canavese, Giacomo Lus, Luigi M E Grimaldi, Marta Zaffira Conti, Giovanna Borriello, Giovanna De Luca, Valentina Tomassini, Alberto Priori, Martina Tosi, Nicola Pomella, Andrea Corona, Alen Zollo, Maria Pia Amato, Eleonora Cocco, Maria Trojano, Filippo Martinelli-Boneschi, Sandra D'Alfonso, Roberto Bergamaschi, Maura Pugliatti","doi":"10.1007/s40120-026-00956-6","DOIUrl":"10.1007/s40120-026-00956-6","url":null,"abstract":"<p><strong>Introduction: </strong>Sun exposure may influence MS susceptibility, but evidence in pediatric-onset MS (PedMS) is limited. We examined whether reduced early-childhood outdoor time (a proxy for lower sun exposure) is associated with PedMS risk.</p><p><strong>Methods: </strong>In the Italian multicenter PEDIGREE Study, environmental data were collected using the PEQ-IT questionnaire. We enrolled individuals < 18 years with PedMS and disease duration ≤ 5 years and controls without CNS inflammatory disorders. Outdoor time was reported by season and age (0-1, 1-2, 3-5 years); reduced activity was defined as < 60 min/week.</p><p><strong>Results: </strong>We included 114 PedMS cases and 121 controls. Cases were 77.2% female; mean (SD) age 16.8 (2.7) years; mean (SD) age at onset 14.2 (2.6) years; median EDSS 1.0 (range 0-4.0). Associations were strongest in winter: reduced outdoor time was associated with higher odds of PedMS in the first year (adjOR 3.02, 95%CI 1.50-6.08), ages 1-2 (adjOR 2.72, 95%CI 1.45-5.09), and ages 3-5 (adjOR 2.66, 95%CI 1.40-5.07). Across ages 0-5, low winter outdoor activity remained strongly associated (adjOR 4.30, 95%CI 1.82-10.17). Other seasons showed weaker but overall significant trends.</p><p><strong>Conclusion: </strong>Limited early-childhood outdoor activity may be associated with increased PedMS risk; larger longitudinal studies are needed.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1829-1844"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Unmet Needs of People with MS at Diagnosis and Throughout Their Care Journey: Insights from a Survey-Based Study.","authors":"Klaus Schmierer, Pieter van Galen, Helen Gray, Alice Laroni, Amanda Montague, Stanca Potra, Heidi Thompson","doi":"10.1007/s40120-026-00942-y","DOIUrl":"10.1007/s40120-026-00942-y","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) has a broad range of symptoms and heterogenous trajectory that requires individualised care. To optimise shared decision-making between healthcare professionals (HCPs) and people with MS (PwMS), it is important to understand communication needs from the patient perspective at diagnosis and throughout their care journey.</p><p><strong>Methods: </strong>Two multinational online surveys were conducted to explore (1) communication needs around the time of diagnosis, and (2) PwMS empowerment in communicating their specific needs and symptoms. Questionnaires included ten close-ended questions and were shared among 100 PwMS aged 18-50 years in Australia, Spain, the UK and the USA. Anonymised data were analysed by a core panel of HCPs, PwMS and patient advocacy group representatives, and key recommendations were agreed.</p><p><strong>Results: </strong>The majority of respondents were female (65-80%) and from the UK (80-87%). PwMS and caregivers are often overwhelmed and feel 'lost' at the time of diagnosis. Early regular contact is critical for effective delivery of key information and building a trusting relationship. PwMS value a clear explanation of the healthcare team and next steps, but only around a quarter (26%) had HCP roles clearly explained. PwMS are often uncertain if health changes are related to MS and 42% reported not feeling comfortable discussing 'invisible' symptoms such as cognitive, mood and emotional changes. Most respondents (54%) reported that their MS nurse was the person they were most likely to consult. Support services were not routinely offered; only 26% were informed about patient support groups. The most reported benefit of an MS-specific patient group was 'feeling less alone'.</p><p><strong>Conclusion: </strong>Regular HCP contact after diagnosis, peer group support for PwMS and their caregivers, signposting of reliable and accurate online resources and the timely offer of support services, including psychological support, should be routine elements of care from the point of diagnosis.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1663-1674"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Radiologically Isolated Syndrome (RIS): A Case with Active Disease 18 Years Later.","authors":"Angelo Ghezzi, Mattia Pozzato, Pietro Annovazzi, Carlo Antozzi, Alessandra Erbetta, Valentina Torri Clerici","doi":"10.1007/s40120-026-00954-8","DOIUrl":"10.1007/s40120-026-00954-8","url":null,"abstract":"<p><strong>Introduction: </strong>Radiologically isolated syndrome (RIS) is defined by incidental MRI findings suggestive of central nervous system (CNS) demyelination in asymptomatic individuals. While uncommon in adults, RIS is exceptionally rare in the pediatric population. Its management, particularly regarding the timing and potential benefits of high-efficacy disease-modifying therapies (DMT), remains debated.</p><p><strong>Case presentation: </strong>We describe a 12-year-old girl who underwent an incidental brain MRI during a school visit, revealing multiple white matter lesions. Despite being asymptomatic, the presence of cerebrospinal fluid oligoclonal bands and a high radiological lesion burden, with evidence of dissemination in space and time during follow-up, indicated a high risk of conversion to multiple sclerosis (MS). Rapid radiological worsening and marked inflammatory activity (multiple gadolinium-enhancing lesions in repeated MRI scans) despite corticosteroid treatment prompted initiation of natalizumab in 2009. Over 18 years of continuous therapy, the patient remained clinically asymptomatic, with no new MRI lesions. The patient maintained an excellent quality of life, successfully completing medical school and residency.</p><p><strong>Conclusions: </strong>In this case of pediatric RIS, early intervention of a high-efficacy DMT prevented clinical conversion to MS, despite aggressive radiological activity in the pre-treatment phase. The patient remained free of clinical and radiological activity over an 18-year follow-up supporting the long-term safety and sustained efficacy of natalizumab, and suggesting that proactive treatment may be beneficial in patients with high-risk RIS.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2189-2196"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence, Persistence, and Safety of Risdiplam in Spinal Muscular Atrophy: A Population-Based Cohort Study.","authors":"Maria Chovi-Trull, Nancy C Ñungo-Garzón, Karolina A Aragon-Gawinska, Inmaculada Pitarch-Castellano, Asunción Albert-Marí, Javier García-Pellicer, José L Poveda-Andrés, María D Edo-Solsona, Juan F Vázquez-Costa","doi":"10.1007/s40120-026-00947-7","DOIUrl":"10.1007/s40120-026-00947-7","url":null,"abstract":"<p><strong>Introduction: </strong>Spinal muscular atrophy (SMA) is a rare neuromuscular disorder caused by biallelic SMN1 variants, partially modulated by SMN2 copy number. Risdiplam, an oral SMN2 splicing modifier, has demonstrated efficacy in SMA. However, long-term adherence and persistence are key to sustaining benefit. We evaluated real-world adherence, persistence, and safety of risdiplam in a population-based cohort.</p><p><strong>Methods: </strong>This was a retrospective observational study including all genetically confirmed SMA type 1-3 patients treated with risdiplam in Spain between January 2020 and October 2025. Adherence was assessed using the proportion of days covered (PDC) from pharmacy dispensing records and the Morisky-Green questionnaire. Persistence was defined as time to permanent discontinuation or switch. Adverse events (AEs) were extracted from clinical records, and Kaplan-Meier analysis was used to estimate persistence probabilities.</p><p><strong>Results: </strong>Fifty-three patients were included (38 adults, 15 pediatric patients); 5.7% had SMA type 1, 52.8% type 2, and 41.5% type 3. One pediatric patient with SMA type 1 was presymptomatic at treatment initiation. Median age at risdiplam initiation was 29 years (interquartile range [IQR] 17-42), and 35.8% had prior nusinersen exposure. Adherence was high: median PDC was 100% (IQR 100-100) at 12 months and throughout follow-up; all patients assessed with the Morisky-Green questionnaire (35/53, 66%) were adherent. At 12 months, 92.5% (49/53) remained on treatment (Kaplan-Meier estimate 94.3%; 95% CI 88.3-100.0). Persistence at 24 and 36 months was 87.8% and 80.1%, respectively; later estimates should be interpreted cautiously because of the limited number of patients at risk. Median treatment duration was 28.1 months. Nine patients (17.0%) discontinued treatment. Treatment-related AEs occurred in 4/53 patients (7.5%), including one pediatric case of leukocytoclastic vasculitis requiring permanent discontinuation.</p><p><strong>Conclusions: </strong>In this real-world population-based cohort, risdiplam showed very high adherence, favorable short- to mid-term persistence, and a favorable safety profile, supporting the feasibility of oral therapy in both pediatric and adult patients with SMA.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1675-1689"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inter-assay and Inter-site Performance of Alpha-Synuclein Seed Amplification Assays in Synucleinopathies: A Multicenter 2 × 2 Protocol Comparison.","authors":"Roger Plaza-Clar, Maximilian Weber, Vaibhavi Kadam, Christian Deuschle, Yihua Ma, Carly M Farris, Luis Concha-Marambio, David Mengel, Marcello Rossi, Angela Mammana, Piero Parchi, Matthis Synofzik, Kathrin Brockmann, Thomas Gasser","doi":"10.1007/s40120-026-00965-5","DOIUrl":"10.1007/s40120-026-00965-5","url":null,"abstract":"<p><strong>Introduction: </strong>The α-synuclein seed amplification assay (synSAA) is a biomarker test for synucleinopathies. Different synSAA conditions have different properties, and some of these conditions enable differentiation between diseases associated with Lewy bodies versus those associated with glial inclusions. Direct cross-assay and inter-site synSAA comparisons evaluating these features remain limited.</p><p><strong>Methods: </strong>Two synSAA conditions (identified here as sodium phosphate buffer (SPB) and piperazine-N,N'-bis(2-ethanesulfonic acid) (PIPES) SAA conditions) were tested in a controlled 2 × 2 design, each performed at two independent laboratories. Cerebrospinal fluid (CSF) from 60 participants was analyzed, comprising 29 multiple system atrophy (MSA) samples and 31 additional CSF samples including 16 Parkinson's disease/dementia with Lewy bodies (PD/DLB) cases previously screened using SPB-SAA conditions, and 15 neurology ward controls, which were used as analytical controls.</p><p><strong>Results: </strong>Inter-site concordance was high for SPB-SAA (100%) and PIPES-SAA (95%, 0.913 Fleiss' kappa). Compared to clinical diagnosis, sensitivity for detecting synSAA+ MSA cases was 75.0% for PIPES-SAA_A and 81.4% for PIPES-SAA_C, with specificities of 76.9% and 92.3%, respectively. SPB-SAA did not detect MSA at either of the two sites and showed 100% specificity. Inter-assay concordance was high for PD/DLB (88%) and controls (86%), but low for MSA (31%), reflecting the different sensitivity in MSA cases. The overall inter-assay concordance yielded a Fleiss' kappa of 0.23.</p><p><strong>Conclusion: </strong>Both synSAA conditions exhibit high reproducibility and replicability across laboratories yet differ in their diagnostic profiles: PIPES-SAA conditions enable detection of synuclein seeds in MSA, while SPB-SAA conditions showed high specificity for PD/DLB but not detect synuclein seeds in MSA. These findings support context-dependent assay selection and underscore the need for larger multicenter validation of analytical tools intended for clinical use.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2153-2166"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Safety and Effectiveness of Lasmiditan in Patients with Migraine: A Post-Marketing Observational Study in Japan.","authors":"Naoko Sanno, Kevin Y Urayama, Joji Mori, Kenichi Yoshizawa, Chie Hashimoto","doi":"10.1007/s40120-026-00966-4","DOIUrl":"10.1007/s40120-026-00966-4","url":null,"abstract":"<p><strong>Introduction: </strong>Migraine is a chronic, disabling neurological disorder affecting the Japanese population, with a significant impact on quality of life and daily activities. Lasmiditan, a selective 5-HT_1F receptor agonist approved for acute migraine treatment, provides an alternative for patients who cannot tolerate or do not respond to existing therapies, including triptans. The study aimed to evaluate the real-world safety and effectiveness of lasmiditan in Japanese patients with migraine as part of post-marketing pharmacovigilance requirements.</p><p><strong>Methods: </strong>This single-arm, multicenter, non-interventional, prospective observational study enrolled 550 patients from 53 medical sites across Japan. Patients newly prescribed lasmiditan for acute migraine between June 2022 and September 2024 were included. Data were collected via electronic case report forms, eDiaries, and questionnaires. Safety assessments included adverse events (AEs), serious AEs (SAEs), and treatment-emergent AEs (TEAEs). Effectiveness was evaluated by pain freedom and pain relief at 2 h post-dose. Data were summarized using descriptive statistics.</p><p><strong>Results: </strong>Of the 400 patients analyzed for safety (mean age 40.5 years; 79.5% female), 56.0% received 50 mg and 42.8% received 100 mg lasmiditan as the initial dose. About 41.8% experienced at least one TEAE, with no SAEs or deaths. The most common TEAEs were dizziness (8.4%) and somnolence (3.9%) with a median time to resolution of 3 and 4 h, respectively. In the effectiveness analysis set (n = 328), for moderate-to-severe headache, 21.5% and 53.9% achieved pain freedom or pain relief, respectively, 2 h post-first dose. For specific daily activities, 45.9% of work or school tasks improved from \"severely disturbed\" and \"couldn't move\" to \"no problem\" or \"slightly disturbed\" after 2 h.</p><p><strong>Conclusions: </strong>Lasmiditan was associated with a manageable safety profile and effectiveness in patients with acute migraine in routine clinical practice in Japan, with no new safety concerns identified.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1807-1827"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}