Neurology and Therapy最新文献

{"title":"Therapeutic Potential of Traditional Chinese Herbal Medicines in Intracerebral Haemorrhage: A Narrative Review.","authors":"Hongyan Guo, Xiaomeng Dong, Xiangjian Zhang, Cong Zhang","doi":"10.1007/s40120-026-01004-z","DOIUrl":"https://doi.org/10.1007/s40120-026-01004-z","url":null,"abstract":"<p><p>Intracerebral haemorrhage (ICH) remains a devastating stroke subtype with limited therapeutic options, creating an urgent need for complementary strategies that target secondary brain injury and recovery. Traditional Chinese herbal medicines (TCHMs) have attracted interest because of their potential multitarget actions on neuroinflammation, oxidative stress, apoptosis, ferroptosis, blood-brain barrier dysfunction, haematoma resolution, gut microbiota dysbiosis and neurovascular repair. Relevant preclinical, clinical and translational studies were identified through a structured search of international and Chinese bibliographic databases. Preclinical studies suggest that selected TCHM-derived bioactive compounds and multicomponent formulae may modulate key pathological processes after ICH, although compound-level mechanisms should not be directly extrapolated to formula-level effects without further validation. Clinically, several small-scale randomized trials, observational studies and meta-analyses have reported potential benefits of selected TCHM preparations, including improved neurological scores, haematoma absorption, oedema reduction and functional recovery when used as adjuncts to conventional care. However, the clinical evidence remains heterogeneous. Larger and more rigorously designed multicentre trials, including CHAIN and CRRICH, have either failed to confirm clear functional benefit or raised safety concerns under specific conditions, particularly regarding ultra-early use of potent blood-activating formulations. Translation into mainstream ICH management is further hindered by variable study quality, insufficient risk-of-bias control, uncertainty regarding active material basis, potential synergistic or antagonistic interactions within multicomponent formulae and limited standardisation of herbal preparations. Future research should focus on formulation-specific, stage-specific and patient-stratified evaluation using rigorous randomized controlled trials, transparent pharmacological characterization, standardised quality control and careful safety monitoring. This review synthesises current evidence from bench to bedside and highlights a cautious pathway toward evidence-based integration of selected TCHMs into ICH management.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762352","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":"Genetic Risk in Multiple Sclerosis: Susceptibility, Modifiers and Unresolved Questions.","authors":"Jingni He, Nicholas B Blackburn, Vilija G Jokubaitis","doi":"10.1007/s40120-026-01009-8","DOIUrl":"https://doi.org/10.1007/s40120-026-01009-8","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterised by inflammation, demyelination and neurodegeneration. The aetiology of MS is complex, arising from interactions among genetic susceptibility, environmental exposures and stochastic immune processes. Over the past 2 decades, large-scale genomic studies have fundamentally shaped our understanding of MS pathogenesis, establishing disease risk as highly polygenic and predominantly driven by immune regulatory mechanisms. Genome-wide association studies (GWAS) have identified 233 common susceptibility variants, including 201 outside the major histocompatibility complex (MHC), with the strongest effects localised to the MHC, particularly HLA-DRB1*15:01. These genetic associations implicate pathways involved in antigen presentation, T- and B-cell activation, cytokine signalling and innate immune responses. Family-based studies have identified putative rare susceptibility variants, but no single gene has been confirmed to cause MS. However, genetic risk alone is insufficient to cause disease, and gene-environment interactions, most notably with Epstein-Barr virus infection, vitamin D insufficiency, obesity, smoking and sex-specific hormonal factors, are critical determinants of disease manifestation. Here, we synthesise current evidence on the genetic architecture of MS, the biological mechanisms linking genetic risk to disease susceptibility and the ways in which genetic factors intersect with environmental exposures to shape clinical outcomes. We further review emerging data on the influence of genetic variation on disease course, prognosis and treatment response. Finally, we discuss unmet needs and future directions, including the role that family studies can play in further informing our understanding of MS pathology, the need for ancestry-diverse studies, multi-omics integration and the translation of genetic insights into clinical care.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766124","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":"Understanding Caregivers' Experiences of Rett Syndrome: A Multinational Study of Symptoms and Meaningful Outcomes of Potential Treatments.","authors":"Bruria Ben-Zeev, Elsa Rossignol, Daniel E Lumsden, Natalie Guido-Estrada, Deborah A Bilder, Monica Coenraads, Sigal Hertz Tirosh, Paige Nues, Sabrina Millson, Rachael Stevenson, John Ashkenas, Chelsea Karbocus, Emily McGinnis, Kristin LaBounty Phillips","doi":"10.1007/s40120-026-01003-0","DOIUrl":"https://doi.org/10.1007/s40120-026-01003-0","url":null,"abstract":"<p><strong>Introduction: </strong>Caregivers have first-hand experience of facing the daily challenges of Rett syndrome (RTT). The aim of this study was to understand caregivers' experiences of RTT, including challenging symptoms that caregivers hope novel therapies will address.</p><p><strong>Methods: </strong>This non-interventional, qualitative and quantitative market research study engaged caregivers of individuals with RTT in the USA, the UK, Canada, and Israel, through an online survey comprising both closed- and open-ended items. Survey domains included age of symptom onset, symptom severity and impact on quality of life, the most challenging symptoms, and caregiver perspectives on meaningful improvement.</p><p><strong>Results: </strong>A total of 323 caregivers completed the survey. Symptoms with the most severe and lasting impact on patients' quality of life typically presented by 6 years of age. These symptoms included loss of speech, loss of purposeful use of hands, and gait disturbances. Caregivers reported a dynamic and lifelong burden associated with impairments in activities of daily living and expressed a desire for improvement across these functional domains following gene therapy treatment.</p><p><strong>Conclusion: </strong>Despite RTT's clinical heterogeneity, similarities emerged in caregivers' daily experiences and their hopes regarding gene therapy treatment. Caregivers believe meaningful improvements for people with RTT would be improved function and enhanced autonomy related to fine and gross motor abilities, and improved ability to communicate needs.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697578","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":"Treatment of Acute Ischemic Stroke with Intravenous Urokinase (TASK-UK): Protocol for a Multicenter, Prospective, Real-World Study.","authors":"Yongli Tao, Hui Fang, Lulu Pei, Yuan Gao, Kai Liu, Xin Wang, Rui Zhang, Zhentang Cao, Yifang Zhou, Ding Zhang, Yiwei Qian, Yuesong Pan, Yuming Xu, Bo Song","doi":"10.1007/s40120-026-01006-x","DOIUrl":"https://doi.org/10.1007/s40120-026-01006-x","url":null,"abstract":"<p><strong>Background: </strong>Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) and urokinase (UK) are both recommended for acute ischemic stroke (AIS) in China. Compared with rt-PA, UK is less expensive and more widely available in clinical practice.</p><p><strong>Objective: </strong>The Treatment of Acute Ischemic Stroke with Intravenous Urokinase (TASK-UK) study aims to investigate clinical outcomes among patients with AIS who receive UK thrombolysis, and to compare efficacy and cost-effectiveness between UK and rt-PA.</p><p><strong>Methods: </strong>TASK-UK is a multicenter, real-world observational study, with a planned sample size of 1000 patients in the UK group and 800 in the rt-PA group. This study enrolls patients with AIS who are eligible for intravenous thrombolysis from 20 participating centers and conducts follow-up until 90 days after thrombolysis.</p><p><strong>Planned outcomes: </strong>The primary efficacy outcome is functional independence at 90 days, defined as a modified Rankin scale (mRS) score of 0-2. The primary safety outcome is symptomatic intracranial hemorrhage (sICH) occurring within 22-36 h after thrombolysis. The exploratory outcome is defined as an intergroup comparison of direct medical costs during hospitalization.</p><p><strong>Discussion: </strong>The TASK-UK study will provide high-quality real-world evidence on the effectiveness and cost-effectiveness of UK thrombolysis for AIS.</p><p><strong>Trial registry number: </strong>NCT06194968 (ClinicalTrials.gov).</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697611","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":"Utilization of Non-pharmacological Interventions in Rett Syndrome: A Systematic Review of the Literature on Supportive Care Management.","authors":"Nazia Rashid, Safiuddin Shoeb Syed, Krithika Rajagopalan, Vinod Kumar Yakkala, Mirko Sikirica, Ismaeel Yunusa","doi":"10.1007/s40120-026-00962-8","DOIUrl":"10.1007/s40120-026-00962-8","url":null,"abstract":"<p><strong>Introduction: </strong>Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by early childhood loss of mobility, reduced verbal communication, and behavioral impairment. Although non-pharmacological supportive interventions are widely used, there is a need to better understand their role in RTT care globally.</p><p><strong>Methods: </strong>Following PRISMA guidelines and a PICOST framework, a systematic review of white (PubMed, Embase, Cochrane) and gray literature was conducted. Non‑pharmacological interventions examined in the United States (US) and outside the US (OUS) settings included ancillary services (e.g., physical therapy [PT]), assistive devices (e.g., wheelchairs), surgical procedures (e.g., scoliosis correction), and assisted interventions (e.g., enteral feeding).</p><p><strong>Results: </strong>Across 28 eligible studies, patient ages ranged from 1 to 66 years, and 71.4% focused exclusively on female patients with RTT. Approximately 25.0% of the studies were conducted in the US, while 75.0% were conducted in OUS. Six studies examined ancillary service use, where PT utilization ranged from 24.4% to 100.0% and occupational therapy (OT) ranged from 11.5% to 91.7%. Pediatric patients demonstrated a two- to fourfold higher utilization of PT and OT services compared to adults. Among six studies evaluating assistive devices, wheelchair use was reported in up to 90.0% of patients. Nine studies reported surgical procedures, with 1.2%-50.0% of patients requiring scoliosis surgery. Eighteen studies examined assisted interventions, showing enteral feeding utilization rates from 2.0% to 52.0%.</p><p><strong>Conclusion: </strong>Despite the universal clinical reliance on non-pharmacological interventions in RTT, the evidence base quantifying their real-world utilization remains sparse. The wide variability in reported rates might be due to differences in data sources, geographic settings, and patient populations which underscores the need for standardized, prospective, longitudinal research. Age-related declines in ancillary service use and geographic gaps highlight systemic disparities that warrant further investigation. These findings provide a foundational evidence base to inform health resource planning and future research priorities in RTT.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1469-1490"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138589","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}