Neurology and Therapy最新文献

{"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":"Stability in Cognition and Employment in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Two-year Phase IV CLARIFY-MS Study.","authors":"Bruno Brochet, Dawn Langdon, Eva Kubala Havrdova, Jeanette Lechner-Scott, Xavier Montalban, Francesco Patti, Fredrik Piehl, Alessandra Solari, Raymond Hupperts, Nektaria Alexandri, Annette Lehn, Andrzej Smyk, Krzysztof Selmaj","doi":"10.1007/s40120-026-00897-0","DOIUrl":"10.1007/s40120-026-00897-0","url":null,"abstract":"<p><strong>Introduction: </strong>Cognitive impairment can affect people with multiple sclerosis (MS) at all stages, negatively impacting their work performance and quality of life. This study aimed to report the cognitive function and employment status data for participants with highly active relapsing MS (RMS) treated with cladribine tablets (CladT) during the 2-year, prospective, open-label, exploratory, single-arm, multicentre, phase IV CLARIFY-MS study.</p><p><strong>Methods: </strong>In this post hoc analysis, changes in cognitive function at month (M)12 and M24 (vs baseline) were measured using the Brief International Cognitive Assessment for MS (BICAMS) battery. Additional analyses were conducted to assess clinically meaningful 4- and 8-point changes in Symbol Digit Modalities Test (SDMT) scores. The employment status of participants was determined through a survey at baseline and M24.</p><p><strong>Results: </strong>BICAMS parameter scores remained stable over 2 years in CladT-treated participants. As determined by a 4- and 8-point change, a high proportion of participants had increased or stable SDMT scores at M24 versus baseline. The mean annualised percentage brain volume change (PBVC) in participants was low. No correlation was found between changes in BICAMS parameter scores and annualised PBVC. Furthermore, no major differences in the employment status of participants were observed over 2 years, with > 40% of participants being in full-time employment during the study.</p><p><strong>Conclusions: </strong>Most CLARIFY-MS participants had increased or stable information processing speed at M24 (vs baseline), as determined using clinically meaningful 4- and 8-point changes in SDMT scores. Overall, the cognitive function and employment status of CladT-treated participants with highly active RMS remained stable over 2 years.</p><p><strong>Trial registry details: </strong>URL: https://clinicaltrials.gov/ct2/show/NCT03369665 ; ClinicalTrials.gov Identifier: NCT03369665.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1491-1507"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434340","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":"The Economic Impact of Cumulative Metabolic Comorbidity Burden in Schizophrenia: A Claims-Based Analysis of Medical Costs in the United States.","authors":"Xue Han, Seth C Hopkins, Zhen Zhang, Shivanshu Awasthi","doi":"10.1007/s40120-026-00973-5","DOIUrl":"10.1007/s40120-026-00973-5","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic comorbidities, including central adiposity, dyslipidemia, insulin resistance, and hypertension, are common in individuals with schizophrenia and contribute to an increased risk of cardiovascular disease and related mortality. There is limited evidence quantifying the economic burden of metabolic comorbidities in schizophrenia. This study aimed to assess the impact of cumulative metabolic comorbidity burden on medical costs in individuals with schizophrenia using claims data.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using the STATinMED Real World Data Insights database covering the period 2018-2024 in the United States (US). Adults with schizophrenia were grouped by number of metabolic comorbidities (obesity, hyperlipidemia, hypercholesterolemia, diabetes, and/or hypertension). Propensity score matching was applied to balance selected baseline characteristics in individuals with and without metabolic comorbidities. The primary outcome was all-cause medical costs, during a 12-month follow-up, adjusted for insurance status and inflation.</p><p><strong>Results: </strong>Overall, 122,248 individuals were eligible. After matching, the numbers for metabolic comorbidities and individuals in each group were: 0, n = 40,552; 1, n = 15,840; 2, n = 11,833; 3, n = 8119; 4, n = 4074; and 5, n = 686. Estimated total medical costs increased with the number of metabolic comorbidities; individuals with five metabolic comorbidities incurred mean costs of US$34,441 per person per year, over 4 times higher than the $8396 cost for individuals with none. A similar pattern was observed for estimated outpatient, inpatient, and stay-related costs, with 3.5-, 2.3- and 1.7-fold increases, respectively.</p><p><strong>Conclusion: </strong>There is a substantial economic burden associated with cumulative metabolic comorbidities in individuals with schizophrenia. Prevention and management of metabolic comorbidities in this population includes early risk assessments, lifestyle modification, and the selection of antipsychotic medications with few metabolic adverse effects. Addressing metabolic comorbidities should be a key component of multidisciplinary care to reduce health-related and economic impacts in schizophrenia.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2011-2026"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259130","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 24-Hour Foslevodopa/Foscarbidopa in Parkinson's Disease: ROSSINI Study 6-Month Interim Results.","authors":"Wolfgang H Jost, Filip Bergquist, Andrew Evans, Sharon Hassin-Baer, Robert A Hauser, Tove Henriksen, Irene A Malaty, Tiago A Mestre, Pablo Mir, Ramon Rodriguez, Petra Schwingenschuh, Mihaela Simu, Lars Bergmann, Teresa T Zhou, Sarah Caughlin, Mallika Gopalkrishnan, Pavnit Kukreja, Marie O'Meara, Juan Carlos Parra, Megha B Shah, Jason Aldred","doi":"10.1007/s40120-026-00948-6","DOIUrl":"10.1007/s40120-026-00948-6","url":null,"abstract":"<p><strong>Introduction: </strong>Foslevodopa/foscarbidopa (LDp/CDp) is a nonsurgical 24-h continuous subcutaneous infusion for patients with advanced Parkinson's disease (aPD) and motor fluctuations uncontrolled on oral medications. We present the first multicountry real-world data from routine clinical practice.</p><p><strong>Methods: </strong>ROSSINI (NCT06107426) is an ongoing 3-year multicountry, prospective, observational study of adults with aPD who are LDp/CDp-naïve (cohort A) or transitioning from LDp/CDp open-label extension studies (NCT04379050/NCT04750226, cohort B). For this interim analysis, the primary endpoint was change from baseline to 6 months in OFF time [Movement Disorder Society Unified Parkinson's Disease Rating Scale Part IV (MDS-UPDRS-IV) modified item 4.3]. Safety was assessed by monitoring adverse events (AEs). Interim results for 105 cohort A patients enrolled ≥ 6 months by March 24, 2025 are presented only; cohort B results were limited (n = 5). Mixed-effects models for repeated measurements (continuous outcomes) were utilized, adjusted for country.</p><p><strong>Results: </strong>Cohort A patients had a mean (SD) age of 68.5 (9.5) years, PD duration of 12.1 (5.3) years, and least squares mean (SE) OFF time of 5.2 (0.6) h at baseline. Patients on LDp/CDp showed statistically significant reductions (95% CI) in OFF time [(- 2.8 h (- 3.6, - 1.9), P ≤ .001, n = 47/40 at baseline/month 6], dyskinesia time [- 1.8 h (- 2.6, - 0.9), P ≤ 0.001], MDS-UPDRS-III [- 5.0 (- 8.2, - 1.9), P = 0.002], Parkinson's Disease Sleep Scale-2 [- 5.2 (- 8.0, - 2.4), P ≤ .001], and 39-item Parkinson's Disease Questionnaire [PDQ-39, - 5.6 (- 9.2, - 2.0), P = .002] from baseline to month 6. Freezing of Gait Questionnaire, Gastrointestinal Dysfunction Scale in PD, and King's PD Pain Scale likewise showed statistically significant decreases (P < .05). Overall, 58 (55.2%) reported ≥ 1 AE, primarily nonserious and mild-to-moderate (12.4% serious, 17.1% severe), with hallucinations and infusion site events the most frequently reported events (5.7% each).</p><p><strong>Conclusions: </strong>ROSSINI demonstrates reductions in motor fluctuations and nonmotor symptoms, and increased quality of life in patients with aPD after 6 months of LDp/CDp treatment. The safety profile was consistent with clinical trials.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT06107426.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1743-1762"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840708","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":"Cenobamate: An Appraisal Five Years On.","authors":"Eugen Trinka, John Paul Leach, Josemir W Sander","doi":"10.1007/s40120-026-00944-w","DOIUrl":"10.1007/s40120-026-00944-w","url":null,"abstract":"<p><p>Cenobamate is an antiseizure medication approved in 2021 as add-on therapy for adults with uncontrolled focal seizures. Early trials showed unusually high seizure freedom rates and a favourable tolerability profile, suggesting that cenobamate may represent an important therapeutic advance in the management of focal and other epilepsies. Here, we highlight the latest data from post hoc analyses and clinical studies suggesting that cenobamate is effective across all focal seizure types. It maintains efficacy and safety over the long term, allowing people to reduce their concomitant medications without compromising seizure control. While head-to-head studies are not available, these data, alongside indirect comparisons with other antiseizure medications, support cenobamate as a potentially important advance in the treatment of focal epilepsy.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1451-1467"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055860","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":"Steroid-Sparing Effect of Efgartigimod in Generalized Myasthenia Gravis: Study Protocol for a Single-Arm, Open-Label Clinical Trial.","authors":"Tetsu Suzuki, Motoki Fujimaki, Shogo Ohuchi, Takashi Hosaka, Ayako Shioya, Shinji Saiki","doi":"10.1007/s40120-026-00980-6","DOIUrl":"10.1007/s40120-026-00980-6","url":null,"abstract":"<p><strong>Introduction: </strong>Oral corticosteroids remain a cornerstone of therapy for generalized myasthenia gravis (gMG) but are associated with substantial long-term toxicity. Efgartigimod, a human immunoglobulin G1 (IgG1) antibody Fc fragment targeting the neonatal Fc receptor (FcRn), has demonstrated efficacy in gMG; however, no prospective trial has evaluated whether regularly scheduled efgartigimod administration can safely reduce oral prednisolone (PSL) dosage. We designed a prospective clinical study to evaluate the steroid-sparing effect of efgartigimod in patients with gMG who remain dependent on ≥ 6 mg/day of oral PSL.</p><p><strong>Methods: </strong>This is a single-arm, open-label, single-center clinical study. Patients with gMG who are receiving ≥ 6 mg/day of oral PSL on a stable dose for at least 4 weeks prior to enrollment, with any concomitant oral immunosuppressants also at stable doses for at least 4 weeks, and scoring ≥ 5 on the MG Activities of Daily Living (MG-ADL) scale will be enrolled. Efgartigimod will be intravenously administered at 10 mg/kg once weekly for 4 consecutive weeks (one cycle), repeated for four cycles with a 28-day interval between cycles. On the fourth administration day of each cycle, oral PSL will be tapered if MG symptoms have not worsened, defined as no ≥ 1-point increase in the MG-ADL score from both baseline and the first administration day of that cycle.</p><p><strong>Planned outcomes: </strong>The primary endpoint is the change in PSL dosage from baseline at the end of the study. Secondary endpoints include the proportion of patients achieving minimal manifestations (MM) or better status with PSL ≤ 5 mg/day (MM-5 mg), the time to reach ≤ 5 mg/day, the cumulative PSL dose over the study period, the proportion of patients completing the protocol, changes in MG-ADL and other clinical scales, responder rate to efgartigimod, comparison of clinical course between MG subtypes (anti-acetylcholine receptor (AChR) antibody-positive, anti-muscle-specific kinase (MuSK) antibody-positive, and double-seronegative cases) and between patients who are anti-AChR antibody positive, with and without thymoma, changes in indicators of steroid toxicity (HbA1c, lumbar spine bone mineral density, and blood pressure), and the safety profile. The study will also explore biomarkers predictive of efgartigimod response through proteomic and immunologic analyses of serially collected blood samples.  Graphical abstract available for this article.  TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT), CRB3180028; registered on 1 October 2024 (prospectively registered).</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2167-2180"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345953","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":"Multidomain Fatigue, Cognitive, and Quality of Life Observations in Generalized Myasthenia Gravis Under Ravulizumab: A Case Series.","authors":"Aurora Zanghì, Paola Sofia Di Filippo, Claudia Rutigliano, Carlo Avolio, Emanuele D'Amico","doi":"10.1007/s40120-026-00974-4","DOIUrl":"10.1007/s40120-026-00974-4","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to explore fatigue and cognitive features as underrecognized non-motor dimensions in myasthenia gravis (MG), and to describe multidomain observations following initiation of ravulizumab in older adults with generalized myasthenia gravis (gMG).</p><p><strong>Methods: </strong>Three acetylcholine receptor antibody-positive older adults with gMG underwent a standardized multidomain evaluation, including clinical outcomes, patient-reported measures of fatigue and quality of life, and performance-based cognitive assessment. Clinical severity was assessed using the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale and the Quantitative Myasthenia Gravis (QMG) score. Fatigue was assessed using the Neuro-QoL Fatigue scale and the Modified Fatigue Impact Scale (MFIS), and quality of life using the Myasthenia Gravis Quality of Life scale (MG-QoL). Cognitive performance was assessed using the Trail Making Test (TMT). Assessments were performed at baseline and repeated after approximately 12 months and analyzed descriptively.</p><p><strong>Results: </strong>Three patients were enrolled. At baseline, MG-ADL scores ranged from 9 to 10 and QMG scores from 10 to 17. Neuro-QoL Fatigue T-scores ranged from 66 to 70, and MFIS total scores from 18 to 43, with MFIS cognitive subscores ranging from 5 to 21. TMT part B completion times ranged from 284 to 300 s in two patients, while one patient was not evaluable. At follow-up, MG-ADL scores were 7, MG-QoL scores ranged from 10 to 14 (from baseline 22-25), Neuro-QoL Fatigue T-scores were lower by 13-17 points, and MFIS total scores were lower by 3, 20, and 9 points across patients. Changes in MFIS cognitive subscores varied, with one patient showing a slight increase (5 → 6) and others showing reductions. One patient transitioned from non-evaluable to evaluable TMT part B performance, while switching cost showed heterogeneous changes across patients.</p><p><strong>Conclusion: </strong>This exploratory case series describes heterogeneous multidomain trajectories across clinical, fatigue, and cognitive measures in gMG. The findings highlight the feasibility of integrating multidomain assessment of non-motor symptoms in this population, without supporting causal inferences regarding treatment effects.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2181-2188"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278259","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":"Observational Retrospective Cohort of Patient Support Program Data on Practical Experiences of Treatment with Foslevodopa/Foscarbidopa in Advanced Parkinson's Disease: The ORCHESTRA Study.","authors":"Tobias Warnecke, Anton Adriaan Van der Plas, Petra Schwingenschuh, Anders Johansson, Mihaela Simu, Marie O'Meara, Resmi Gupta, Bjoern Fritz, Lars Bergmann, Juan Carlos Parra, Martin Südmeyer","doi":"10.1007/s40120-026-00978-0","DOIUrl":"10.1007/s40120-026-00978-0","url":null,"abstract":"<p><strong>Introduction: </strong>Foslevodopa/foscarbidopa (LDp/CDp) is a continuous 24-h subcutaneous infusion therapy for advanced Parkinson's disease (aPD). Clinical trials have demonstrated the efficacy and safety of LDp/CDp; however, real-world evidence is limited.</p><p><strong>Methods: </strong>This retrospective multi-country cohort study used data recorded by AbbVie's patient support program (PSP) nurses during routine interactions with patients with aPD on LDp/CDp (December 2023-February 2025). Patients were followed until earliest of treatment discontinuation or database lock. Patients who started therapy during the study period were included without a pre-defined follow-up duration or standardized scheduled visits.</p><p><strong>Results: </strong>A total of 2590 patients (38.3% female) were followed on average for 141.1 days. During follow-up, mean LDp/CDp base infusion rate was 0.36 (SD = 0.14) mL/h, equivalent to 62.0 (SD = 23.6) mg/h. During the optimization period (mean = 5.4 days), infusion rates generally increased from initial recorded dose to optimization, then remained stable. Among participants with available effectiveness data, 60.0% and 83.0% reported 0 h/day of \"Off\" and dyskinesia symptoms, respectively, in the first month post-optimization; with similar observations over time. 61.1% of patients were assessed as handling the pump well and 80.5% as applying skin care well during the optimization period; both increased post-optimization. The most common reason for discontinuation was infusion site events (5.1%). Exploratory results indicated that younger patients (< 65 years) with shorter disease duration (< 10 years), managed the system better and had more favorable discontinuation outcomes compared to the total population.</p><p><strong>Conclusion: </strong>This study describes real-world use of LDp/CDp in patients with aPD demonstrating that a stable infusion rate was achieved within 5.4 days and provides initial observations on effectiveness. Data completeness varied substantially across variables due to the non-mandatory nature of data collection within the PSP and variable follow up duration. Ongoing efforts to improve data completeness and standardization will support future analyses and enhance understanding of real-world use of LDp/CDp and patient's experience.</p><p><strong>Clinical trial registration: </strong>The study is registered on ClinicalTrials.gov under NCT06937034.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2073-2095"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295783","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}