Neurology and Therapy最新文献

{"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}

{"title":"Eculizumab in Myasthenia Gravis: A Multicenter Retrospective Real-World Study in China.","authors":"Yue Li, Huan Yang, Song Tan, Lijun Luo, Xuebing Cao, JinQuan Hu, Bitao Bu, Ting Chang, Zhijun Li","doi":"10.1007/s40120-026-00977-1","DOIUrl":"10.1007/s40120-026-00977-1","url":null,"abstract":"<p><strong>Introduction: </strong>Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder needing long-term immunosuppressive therapy. Eculizumab is a promising treatment, but real-world evidence on its efficacy and safety is limited.</p><p><strong>Methods: </strong>This retrospective cohort study across six medical centers enrolled 60 patients with MG on eculizumab. Clinical data, including MG-Activities of Daily Living (MG-ADL) scores, quantitative MG scores (QMG), and oral corticosteroid dosage at baseline, weeks 1, 4, and 8, and final follow-up were obtained. Outcomes included score changes, post-intervention status (PIS), and safety profile.</p><p><strong>Results: </strong>By week 8, 30.95% of patients achieved minimal manifestation status (MMS) or better, increasing to 32.69% at final follow-up. Mean ADL scores significantly dropped from 8.18 ± 3.99 at baseline to 5.59 ± 3.72 at week 1, 3.78 ± 3.42 at week 4, 3.50 ± 2.92 at week 8, and 3.33 ± 3.56 during final follow-up (p < 0.0001). Clinically meaningful improvement (CMI) was observed in 56.9%, 70.0%, 85.0%, and 76.27% at the respective time points. Both thymoma-associated and non-thymoma subgroups showed significant ADL improvement (p ≤ 0.026) with mixed-effects modeling revealing significant group × time interaction (p = 0.01).The thymoma-associated MG (TAMG) group had a faster initial response, with subsequent outcomes comparable between the two groups. Among the 37 patients (61.67%) who switched from FcRn inhibitor therapy to eculizumab, clinical outcomes were non-inferior to those of direct eculizumab recipients and the magnitude of MG-ADL improvement was comparable to that of the overall treatment group. The mean daily corticosteroid dose decreased from 21.21 ± 13.68 mg at baseline to 13.32 ± 10.42 mg at final follow-up (p < 0.0001) Adverse events were rare, with no treatment-related serious events.</p><p><strong>Conclusion: </strong>Eculizumab provides rapid and sustained clinical improvement in patients with MG, with a favorable safety profile. Patients with TAMG show a faster initial response. For patients with an inadequate response to FcRn inhibitors, eculizumab remains an effective rescue strategy.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1973-1992"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218790","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":"Safety and Efficacy of Obinutuzumab β (MIL62), a Novel Glycoengineered Type II Anti-CD20 Monoclonal Antibody, in Patients with Neuromyelitis Optica Spectrum Disorder: A Multicenter, Single-Arm, Phase Ib Clinical Trial.","authors":"Lei Wu, Min Wei, Feng Gao, Hua Zhang, Jiawei Wang, Feng Xiang, Sai Gao, Ran Liu, Jian Yin, Yanjun Guo, Xifang Liu, Jinjin Liang, Sijun Liu, Feng Li, Dehui Huang","doi":"10.1007/s40120-026-00960-w","DOIUrl":"10.1007/s40120-026-00960-w","url":null,"abstract":"<p><strong>Introduction: </strong>To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of obinutuzumab β, a novel glycoengineered type II anti-CD20 monoclonal antibody, in patients with neuromyelitis optica spectrum disorder (NMOSD).</p><p><strong>Methods: </strong>In this multicenter, open-label, single-arm, phase Ib trial (NCT05314010), 11 aquaporin protein-4 (AQP4)-IgG-positive patients with NMOSD received obinutuzumab β at 500 mg or 1000 mg on days 1 of weeks 1 and 3. Patients in the 500-mg group could escalate to 1000 mg after 24 weeks if tolerated. Evaluations occurred at specified weeks (24-208), with 1000-mg doses on days 1 of weeks 25, 27, and every 26 weeks thereafter in patients who are relapse-free. Safety, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity were assessed.</p><p><strong>Results: </strong>All participants with 500 mg (n = 3) transitioned to 1000 mg after 24 weeks. During the entire study period, all 11 participants experienced at least one treatment-emergent adverse event (TEAE); 90.9% had treatment-related adverse events (TRAEs). Serious adverse events were reported in 54.5%, with 27.3% related to obinutuzumab β. No TEAEs or TRAEs led to treatment discontinuation, withdrawal, or death. Two patients had early relapses on days 26 and 27 post-first dose, respectively; one withdrew immediately, while the other remained on treatment for 1 year. The 2-year disease relapse-free rate was 81.8% [95% confidence interval (CI): 44.7%, 95.1%], and the annualized relapse rate (ARR) declined from 1.3 before 2-year treatment to 0.2 (95% CI: 0.1, 0.2) after obinutuzumab β, representing an 87.7% reduction.</p><p><strong>Conclusion: </strong>Obinutuzumab β demonstrated manageable safety and may have promising efficacy against NMOSD. Despite the lack of a comparator group, the results support evaluation in phase III trials.</p><p><strong>Clinical trial registration: </strong>https://clinicaltrials.gov/ (#NCT05314010).</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1845-1862"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005957","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":"Digital Motor Outcomes Capture Upper Limb and Mild Stage Impairment in Hereditary Spastic Paraplegia.","authors":"Malin Schulze, Dominik Hermle, Robin Schubert, Pascal Barallon, Winfried Ilg, Rebecca Schüle, Ralf Reilmann, Matthis Synofzik, Andreas Traschütz","doi":"10.1007/s40120-026-00950-y","DOIUrl":"10.1007/s40120-026-00950-y","url":null,"abstract":"<p><strong>Introduction: </strong>Digital motor outcomes may surpass the sensitivity of clinician-reported outcomes in hereditary spastic paraplegia (HSP), particularly in cases of mild upper limb impairment and early disease stages. We thus validated a trial-ready quantitative motor (Q-Motor) assessment of rapid alternating limb movement tasks against clinician-reported, patient-focused, and performance outcomes in HSP.</p><p><strong>Methods: </strong>Exploratory single-center cross-sectional assessment in 41 patients with different HSP genotypes (age: 48 ± 14 years), with speeded foot tapping, diadochokinesia, and finger tapping measured by a high-resolution force transducer. Validation comprised discrimination from 48 age- and sex-matched controls; correlations to the Spastic Paraplegia Rating Scale (SPRS; mean: 18.6 ± 9.1), Friedreich Ataxia Rating Scale- Activities of Daily Living (FARS-ADL), and Nine-Hole Peg Test (9HPT); and stratification by functional stage (FARS stage: mild/moderate/severe = ambulatory/walking aid/wheelchair).</p><p><strong>Results: </strong>Foot tapping best discriminated patients with HSP from controls (e.g., frequency: area under the curve [AUC] = 0.94-0.96), and particularly captured HSP severity and functional impairment by measures of foot elevation and cumulative tap force (across all measures: |rho_SPRS|= 0.33-0.59; |rho_ADL|= 0.35-0.56). Speed measures of diadochokinesia and finger tapping captured functional impairment (|rho_ADL|= 0.32-0.60) and impaired dexterity (|rho_9HPT |= 0.53-0.77) in the upper limbs of patients with HSP-even in the mild stage, and with slowed finger tapping even in patients without upper limb pyramidal signs. Foot tapping measures were most sensitive in discriminating mild-stage impairment (AUC = 0.72-0.95) and predominantly changed between mild and moderate HSP, while upper limb measures of diadochokinesia and finger tapping predominantly changed from moderate to severe HSP.</p><p><strong>Conclusion: </strong>Q-Motor captures motor impairment in HSP, even in the upper limbs and mild disease stages, and should be further evaluated as a possible trial outcome by longitudinal validation in genotypically stratified cohorts and mapping to patient experience.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1993-2009"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259126","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":"Treatment Preferences for Subcutaneous Immunoglobulin Among Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Caregivers, and Physicians: A Discrete Choice Experiment.","authors":"Min Yang, Miriam L Zichlin, Chelsey Fix, Danni Yang, Mo Zhou, Lisa Butler, Hakan Ay, Colin Anderson-Smits","doi":"10.1007/s40120-026-00915-1","DOIUrl":"10.1007/s40120-026-00915-1","url":null,"abstract":"<p><strong>Introduction: </strong>Subcutaneous immunoglobulin (SCIG) is a recommended maintenance treatment option for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and could offer greater patient convenience than intravenous immunoglobulin (IVIG). We evaluated the burden of CIDP and assessed the value that patients with CIDP, caregivers, and physicians place on various attributes of SCIG treatment options.</p><p><strong>Methods: </strong>This was an online discrete choice experiment survey designed through targeted literature review and patient/caregiver/physician interviews, conducted in Germany, the UK, and the USA. The survey was administered to adults with CIDP who were stable on IVIG and/or receiving SCIG, and caregivers/physicians. Participants chose preferred treatment profiles comprising six SCIG treatment attributes with varying levels: chance of CIDP symptom worsening, treatment frequency, number of sites per infusion, time spent on infusion per month, chance of infusion site reaction, and infusion location. Subgroup analyses were also performed. A conditional logistic regression model estimated preference weight for each attribute.</p><p><strong>Results: </strong>Overall, 146 patients, 52 caregivers, and 81 physicians completed the survey; mean (standard deviation) patient age was 58.1 (12.8) years; time since CIDP diagnosis was 8.8 (9.3) years; 98.6% had received IVIG, and 30.8% had received SCIG. Patients and caregivers experienced a substantial burden of disease that negatively impacted quality of life and work productivity. The most important factors in treatment decision-making were a lower chance of CIDP symptom worsening in 6 months, less frequent treatment administration, and home infusion (all p < 0.001 vs reference categories). Patients considered a lower chance (10% vs 20%) of symptom worsening and lower treatment frequency (every 3-4 weeks vs weekly) as the most important SCIG attributes, accounting for 64.6% of the decision weight.</p><p><strong>Conclusion: </strong>There remains a substantial burden on patients and caregivers due to CIDP. Patients with CIDP highly valued efficacy and convenience when considering preferred SCIG options. Preference awareness may facilitate shared patient-physician decision-making.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1721-1742"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840704","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":"A Multimodal Latent Severity Axis for Alzheimer's Disease: Probabilistic PCA, Bayesian Trajectories, and Stage-Aware Timing Effects.","authors":"Babak Haji, Amir Abbas Tahami Monfared","doi":"10.1007/s40120-026-00940-0","DOIUrl":"10.1007/s40120-026-00940-0","url":null,"abstract":"<p><strong>Introduction: </strong>Multimodal Alzheimer's disease (AD) cohorts capture cognition, function, neuroimaging, and fluid biomarkers, yet overall disease severity remains difficult to summarize on a single clinically meaningful scale. The apolipoprotein E ε4 (APOE ε4) allele is the strongest common genetic risk factor for late-onset AD, but its association with \"progression\" has been inconsistent because earlier placement along the disease continuum is often conflated with faster within-stage decline.</p><p><strong>Methods: </strong>Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we analyzed an amyloid-positive baseline cohort (N = 1058) and a longitudinal subset (N = 932; ≥ 2 visits and ≥ 4 of 13 measures per visit). Measures included standardized cognitive and functional assessments, structural and functional neuroimaging, cerebrospinal fluid biomarkers of amyloid‑beta and tau pathology, and plasma neurofilament light protein as a marker of neuroaxonal injury. Magnetic resonance imaging (MRI) volumes were adjusted using amyloid-negative cognitively normal controls with quadratic age and intracranial volume terms. Probabilistic principal component analysis (PPCA) was used to derive a latent severity coordinate, defined as the first principal component (PC1). Hierarchical Bayesian random-intercept and random-slope models were used to estimate individual trajectories, partition APOE ε4 effects into baseline severity and within-stage rate, and generate genotype-stratified ages at prespecified severity landmarks. Axis stability was assessed with 100 bootstrap refits, and predictive performance was assessed with participant-level fivefold cross-validation.</p><p><strong>Results: </strong>The PC1 explained 38.7% of baseline variance and produced a clinically interpretable multimodal severity axis. Stability was high across bootstrap refits, and residual association with age was minimal after MRI volume adjustment. Higher APOE ε4 dose was associated with greater baseline latent severity, whereas within-stage rate differences were smaller than the baseline severity-position effect. A latent symptomatic landmark was reached approximately 3.0-3.3 years earlier per ε4 allele. Adding APOE improved out-of-sample prediction by about 10% without loss of calibration.</p><p><strong>Conclusions: </strong>Probabilistic principal component analysis provides a stable, multimodal, biologically informed severity axis for longitudinal modeling in amyloid-positive ADNI. Within this framework, APOE ε4 was associated primarily with latent severity position and model-implied timing along the continuum, whereas within-stage rate differences were smaller. These findings support stage-aware longitudinal inference and methodological applications within this cohort, while external clinical calibration and validation remain necessary.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1643-1662"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777302","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}