Therapeutic Advances in Neurological Disorders最新文献

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Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study. 阿仑妥珠单抗对高度活动性多发性硬化症患者的长期疗效和安全性:TOPAZ 临床试验和 TREAT-MS 真实世界研究的中期分析。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.1177/17562864241306575
Tjalf Ziemssen, Ann D Bass, Bart Van Wijmeersch, Sara Eichau, Stephan Richter, Frank Hoffmann, Nicole M Armstrong, Magdalena Chirieac, Janete Cunha-Santos, Barry A Singer
{"title":"Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study.","authors":"Tjalf Ziemssen, Ann D Bass, Bart Van Wijmeersch, Sara Eichau, Stephan Richter, Frank Hoffmann, Nicole M Armstrong, Magdalena Chirieac, Janete Cunha-Santos, Barry A Singer","doi":"10.1177/17562864241306575","DOIUrl":"10.1177/17562864241306575","url":null,"abstract":"<p><strong>Background: </strong>Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9 years was observed in the phase IIIb/IV open-label TOPAZ clinical trial and assessed in the real-world retrospective and prospective study, TREAT-MS.</p><p><strong>Objectives: </strong>To examine long-term efficacy and safety of alemtuzumab in participants with multiple sclerosis (MS) and highly active disease (HAD) by combining up to 13 years of TOPAZ data and TREAT-MS interim data.</p><p><strong>Design: </strong>TOPAZ: Randomized participants completing core CARE-MS I and II could receive additional alemtuzumab (12 mg/day, 3 consecutive days; ⩾12 months apart) for 11-13 years after initiating treatment. TREAT-MS: Participants from German MS clinics were observed for 4 years after last alemtuzumab treatment phase.</p><p><strong>Methods: </strong>Efficacy outcomes (annualized relapse rate (ARR), change in Expanded Disability Status Scale (EDSS), 6-month confirmed disability worsening/improvement, magnetic resonance imaging), and adverse events (AEs) were examined. Primary HAD definition (⩾2 relapses in the year prior to baseline and ⩾1 gadolinium-enhancing lesion at baseline), and two alternative HAD definitions were assessed.</p><p><strong>Results: </strong>More participants from CARE-MS I (28%) and II (24%) met primary HAD criteria than TREAT-MS (~14%). Mean ARR for alemtuzumab-treated HAD participants was significantly reduced in CARE-MS I and II (0.14 and 0.15, respectively, Years 3-13) and in TREAT-MS (0.24, <b>></b>2 years). Stable/improved EDSS scores were achieved by 74% of HAD participants in CARE-MS I, 67% in CARE-MS II (both Year 11), and 79% in TREAT-MS (Year 3.6), with 6-month CDI achieved by about half at Year 11 (CARE-MS I, II). Annual treatment-emergent AE incidences declined in TOPAZ and were lower in TREAT-MS.</p><p><strong>Conclusion: </strong>Sustained efficacy of alemtuzumab was observed for clinical and radiological outcomes in participants with HAD in the TOPAZ clinical trial and real-world TREAT-MS study with no new safety signals.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (CARE-MS I, NCT00530348; CARE-MS II, NCT00548405; CARE-MS Extension Study, NCT00930553; TOPAZ, NCT02255656). Paul-Ehrlich-Institut (TREAT-MS, NIS 281).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241306575"},"PeriodicalIF":4.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug-induced dementia: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database. 药物性痴呆:使用FDA不良事件报告系统数据库的现实世界药物警戒研究。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-28 eCollection Date: 2025-01-01 DOI: 10.1177/17562864251315137
Lisi Xu, Ruonan Zhang, Xiaolin Zhang, Xiuli Shang, Daifa Huang
{"title":"Drug-induced dementia: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database.","authors":"Lisi Xu, Ruonan Zhang, Xiaolin Zhang, Xiuli Shang, Daifa Huang","doi":"10.1177/17562864251315137","DOIUrl":"https://doi.org/10.1177/17562864251315137","url":null,"abstract":"<p><strong>Background: </strong>Dementia is a serious adverse event (AE) that requires attention in clinical practice. However, information on drug-induced dementia is limited. The U.S. FDA Adverse Event Reporting System (FAERS) serves as an important resource for identifying real-world adverse drug reactions and safety signals.</p><p><strong>Objective: </strong>This study aimed to use FAERS data to identify drugs associated with increased dementia risk.</p><p><strong>Design: </strong>A secondary analysis of the FAERS database was conducted using disproportionality analysis methods.</p><p><strong>Methods: </strong>We reviewed dementia-related reports in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023, used the Medical Dictionary for Regulatory Activity to identify dementia cases and summarized the corresponding list of potential medications, counted the dementia-causing medication classes with the highest frequency of reports, and disaggregated all medications.</p><p><strong>Results: </strong>The study identified 31,881 dementia-related AEs in the FAERS database, with an increasing trend over time, particularly among females and individuals over 65. Apixaban had the most reports (1631). Disproportionality analyses revealed that rivastigmine, nicergoline, aducanumab, amlodipine/atorvastatin, and dihydroergometrine had the highest risk, based on reporting odds ratio, proportional reporting ratio, and information component. Only valproate and tramadol among the top 50 drugs included a potential dementia risk in their package inserts.</p><p><strong>Conclusion: </strong>This study identified a list of medications associated with dementia risk, many of which lack dementia warnings on their labels. Increased monitoring is necessary for high-risk individuals, and further research is required to clarify these associations and improve patient safety.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251315137"},"PeriodicalIF":4.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The use of cannabidiol as adjunctive therapy in adult patients with drug-resistant epilepsy: a systematic review and meta-analysis. 大麻二酚作为成人耐药癫痫患者的辅助治疗:一项系统综述和荟萃分析。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-28 eCollection Date: 2025-01-01 DOI: 10.1177/17562864251313914
Marjorie Jia Yi Ong, Muhammad Samir Haziq Abd Rahman, Vanessa Lin Lin Lee, Kong Heng Lee, Carmen Jia Yinn Chang, Ching Soong Khoo, Rozita Hod, Hui Jan Tan, Eugen Trinka
{"title":"The use of cannabidiol as adjunctive therapy in adult patients with drug-resistant epilepsy: a systematic review and meta-analysis.","authors":"Marjorie Jia Yi Ong, Muhammad Samir Haziq Abd Rahman, Vanessa Lin Lin Lee, Kong Heng Lee, Carmen Jia Yinn Chang, Ching Soong Khoo, Rozita Hod, Hui Jan Tan, Eugen Trinka","doi":"10.1177/17562864251313914","DOIUrl":"https://doi.org/10.1177/17562864251313914","url":null,"abstract":"<p><strong>Background: </strong>Highly purified cannabidiol (CBD), recently approved for various neurological disorders, is explored as a potential therapeutic avenue for drug-resistant epilepsy (DRE) among adult people with epilepsy (PWE) in this systematic review and meta-analysis.</p><p><strong>Objectives: </strong>To conduct an extensive literature review and meta-analysis of CBD use for DRE in adult PWE.</p><p><strong>Design: </strong>Systematic review and meta-analysis.</p><p><strong>Data sources and methods: </strong>We conducted a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and two electronic resources; we searched Ovid MEDLINE and Scopus using appropriate keywords until August 2023. Data were presented as standardized mean difference (SMD) and odds ratio with confidence interval (CI) via random effect. We appraised the risk of bias of the included studies using the Joanna Briggs Institute critical appraisal tool while their strength of evidence with the Oxford Centre for Evidence-Based Medicine (OCEBM) and Grading of Recommendations Assessment Development and Education (GRADE) Levels of Evidence.</p><p><strong>Results: </strong>We identified 16 studies, 3 of which were randomized controlled trials and 3 prospective cohort studies, while the rest were expanded access programs, deriving a total of 668 participants receiving CBD for seizure control. CBD was used concomitantly with antiseizure medications in all studies. There was a statistically significant seizure reduction in the group receiving CBD therapy compared to the placebo group (SMD: -1.50, 95% CI (-3.47, 0.47), <i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>The evidence on CBD use in adult patients with DRE demonstrates a moderate level of certainty according to GRADE level and OCEBM level 2. Further prospective studies involving multiple centers are encouraged to study both the efficacy and safety of CBD in adult patients with DRE.</p><p><strong>Trial registration: </strong>International Prospective Register of Systematic Reviews (PROSPERO) 2023 CRD42023449955.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251313914"},"PeriodicalIF":4.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A multi-country cohort database study to assess pregnancy and infant outcomes after potential maternal or paternal exposure to cladribine tablets in the treatment of multiple sclerosis: the CLEAR study methods and status update. 一项多国队列数据库研究,评估母亲或父亲在多发性硬化症治疗中暴露于克拉德滨片剂后的妊娠和婴儿结局:CLEAR研究方法和状态更新。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-27 eCollection Date: 2025-01-01 DOI: 10.1177/17562864241310996
Kerstin Hellwig, Melinda Magyari, Thomas M MacDonald, Carolyn E Cesta, Stig Wergeland, Maarit K Leinonen, Asher Ornoy, Sandra Vukusic, Alexandra Lauer, Xiaolei Zhou, Alison Kawai, Rachel Weinrib, Alejandro Arana, Tahani Boumenna
{"title":"A multi-country cohort database study to assess pregnancy and infant outcomes after potential maternal or paternal exposure to cladribine tablets in the treatment of multiple sclerosis: the CLEAR study methods and status update.","authors":"Kerstin Hellwig, Melinda Magyari, Thomas M MacDonald, Carolyn E Cesta, Stig Wergeland, Maarit K Leinonen, Asher Ornoy, Sandra Vukusic, Alexandra Lauer, Xiaolei Zhou, Alison Kawai, Rachel Weinrib, Alejandro Arana, Tahani Boumenna","doi":"10.1177/17562864241310996","DOIUrl":"10.1177/17562864241310996","url":null,"abstract":"<p><strong>Background: </strong>Cladribine tablets are contraindicated during pregnancy; therefore, safety data on pregnancies exposed to this treatment are limited. CLEAR collects and describes pregnancy outcomes in this understudied population.</p><p><strong>Objectives: </strong>To describe the main features of the CLEAR study design, including the data sources and the methodological approach, and provide a status update.</p><p><strong>Design: </strong>CLEAR is a non-interventional, multi-database, comparative cohort study. Four cohorts are included: pregnancies of women with multiple sclerosis (MS) exposed to cladribine tablets (maternal cohort exposed); pregnancies of women with MS unexposed to any disease-modifying therapy (DMT; maternal cohort unexposed); pregnancies fathered by men with MS exposed to cladribine tablets; and pregnancies fathered by men with MS unexposed to any DMT.</p><p><strong>Methods: </strong>A staggered methodological approach, using data from Denmark, Finland, France, Germany, Norway, Scotland, and Sweden, will be applied to analyze the occurrence of major congenital anomalies (primary outcome) and selected pregnancy outcomes. The first interim analysis (performed using German pregnancy cohorts) was conducted when ⩾75 pregnant women (including 25 women from the maternal cohort exposed) were cumulatively reached across all participating countries. The end of the study period will be established once pregnancy counts reach 149 in the maternal cohort exposed and 298 in the maternal cohort unexposed in all countries combined, or 5 years after pregnancy counts are first assessed (whichever occurs first).</p><p><strong>Results: </strong>As of January 2024, data on pregnancies of women exposed to cladribine tablets (<i>n</i> = 28-36 (numbers are approximate due to masking of some counts)), and pregnancies of women unexposed to cladribine tablets (<i>n</i> = 2834) were available from Denmark, Finland, Germany, Scotland, and Sweden.</p><p><strong>Conclusion: </strong>The CLEAR study, using a staggered methodological approach, aims to provide further insight into the safety outcome data for cladribine tablets in pregnant women, as a regulatory commitment with the European Medicines Agency.</p><p><strong>Trial registration: </strong>EU PAS Register number, EUPAS25027.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241310996"},"PeriodicalIF":4.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vaccination coverage and its determinants in patients with multiple sclerosis-a multicenter cross-sectional study. 多发性硬化症患者的疫苗接种覆盖率及其决定因素——一项多中心横断面研究
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-24 eCollection Date: 2025-01-01 DOI: 10.1177/17562864241309806
Paula Schade, Hai-Anh Nguyen, Julia Steinle, Kerstin Hellwig, Teodor Pelea, Philipp Franken, Birte Elias-Hamp, Veit Becker, Stefan Merkelbach, Stephan Richter, Bert Wagner, Christian Geis, Matthias Schwab, Florian Rakers
{"title":"Vaccination coverage and its determinants in patients with multiple sclerosis-a multicenter cross-sectional study.","authors":"Paula Schade, Hai-Anh Nguyen, Julia Steinle, Kerstin Hellwig, Teodor Pelea, Philipp Franken, Birte Elias-Hamp, Veit Becker, Stefan Merkelbach, Stephan Richter, Bert Wagner, Christian Geis, Matthias Schwab, Florian Rakers","doi":"10.1177/17562864241309806","DOIUrl":"10.1177/17562864241309806","url":null,"abstract":"<p><strong>Background: </strong>Complete vaccination coverage is recommended by multiple sclerosis (MS) societies for patients with multiple sclerosis (pwMS) to mitigate infection risks associated with disease-modifying therapies (DMTs).</p><p><strong>Objectives: </strong>To analyze vaccination coverage and its determinants in pwMS compared to healthy controls, considering vaccination hesitancy, MS-specific vaccination beliefs, trust in information sources, and the role of general practitioners (GPs).</p><p><strong>Methods: </strong>This cross-sectional multicenter observational study was conducted in six German MS centers. The primary endpoint was a vaccination index (VI) comprising eight standard vaccinations (range 0-1, with higher VI indicating better vaccination coverage). Secondary endpoints included validated measures of general vaccination hesitancy, MS-specific vaccination beliefs, and trust in information sources. Data were collected through questionnaires, vaccination card analysis, and a survey of GPs who vaccinate pwMS.</p><p><strong>Results: </strong>VI tended to be lower in pwMS (<i>n</i> = 397) compared to healthy controls (<i>n</i> = 300; 0.58 ± 0.30 vs 0.62 ± 0.31, <i>p</i> = 0.057). In pwMS receiving highly effective DMTs, VI did not differ significantly from those on no/platform DMTs. Vaccination hesitancy was comparably low, with no differences between pwMS and controls. Vaccination hesitancy, beliefs, and trust in information sources explained only 10%-16% of the variance in VI. Among 109 GPs, 82% cited reluctance to vaccinate pwMS due to concerns about MS-related side effects or interactions with DMTs.</p><p><strong>Conclusion: </strong>Despite clear recommendations from MS societies for full vaccination of all pwMS, vaccination coverage remains worryingly low. Approximately half of the patients lack standard vaccination coverage, even those on highly effective DMTs. In fact, vaccination coverage in pwMS tended to be even lower than in healthy controls. Vaccination hesitancy and other intrinsic factors do not sufficiently explain the low vaccination rates. Inconsistent vaccination recommendations from GPs due to uncertainties about vaccine safety and DMT interactions likely contribute.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241309806"},"PeriodicalIF":4.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum to "Chronic active lesions in multiple sclerosis: classification, terminology, and clinical significance". “多发性硬化症慢性活动性病变:分类、术语和临床意义”的勘误。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-24 eCollection Date: 2025-01-01 DOI: 10.1177/17562864251316382
{"title":"Erratum to \"Chronic active lesions in multiple sclerosis: classification, terminology, and clinical significance\".","authors":"","doi":"10.1177/17562864251316382","DOIUrl":"https://doi.org/10.1177/17562864251316382","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/17562864241306684.].</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251316382"},"PeriodicalIF":4.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oral supplementation with propionate is reflected in the serum of healthy individuals. 口服丙酸盐的补充反映在健康个体的血清中。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-23 eCollection Date: 2025-01-01 DOI: 10.1177/17562864241309755
Maximilian Schröder, Arijan Pasic, Frank Hirche, Svitlana Rozanova, Melissa Sgodzai, Barbara Gisevius, Lea Horstkemper, Ralf Gold, Katrin Marcus, Kalliopi Pitarokoili, Jeremias Motte, Katalin Barkovits, Gabriele Stangl, Anna Lena Fisse
{"title":"Oral supplementation with propionate is reflected in the serum of healthy individuals.","authors":"Maximilian Schröder, Arijan Pasic, Frank Hirche, Svitlana Rozanova, Melissa Sgodzai, Barbara Gisevius, Lea Horstkemper, Ralf Gold, Katrin Marcus, Kalliopi Pitarokoili, Jeremias Motte, Katalin Barkovits, Gabriele Stangl, Anna Lena Fisse","doi":"10.1177/17562864241309755","DOIUrl":"10.1177/17562864241309755","url":null,"abstract":"<p><strong>Background: </strong>Short-chain fatty acids (SCFAs), including propionic acid (PA), are key in immunological research. Supplementing PA has shown benefits for autoimmune diseases. A comprehensive understanding of the PA pharmacokinetics is essential for the optimal design and execution of studies utilizing orally administered PA.</p><p><strong>Objective: </strong>We propose two methods of measuring PA in serum, carried out by different laboratories.</p><p><strong>Design: </strong>Blood samples from 20 volunteers were collected hourly following PA supplementation.</p><p><strong>Methods: </strong>Serum propionate quantification was performed with two independent mass spectrometry-based (MS) analyses, including liquid-chromatography (LC)-MS and direct-infusion (DI)-MS.</p><p><strong>Results: </strong>PA levels increased within 1 h of ingestion of 500 mg PA. Serum concentrations ranged from 1.3 to 4.5 µmol/L, rising significantly after 1 h (<i>p</i> < 0.05). Serum levels returned to baseline within 2 h. No significant differences were found regarding sex or diet.</p><p><strong>Conclusion: </strong>The shown pharmacokinetics can be used in future PA research.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241309755"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tofersen and other antisense oligonucleotides in ALS. 肌萎缩侧索硬化症中的托佛森和其他反义寡核苷酸。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-22 eCollection Date: 2025-01-01 DOI: 10.1177/17562864251313915
Albert Ludolph, Maximilian Wiesenfarth
{"title":"Tofersen and other antisense oligonucleotides in ALS.","authors":"Albert Ludolph, Maximilian Wiesenfarth","doi":"10.1177/17562864251313915","DOIUrl":"10.1177/17562864251313915","url":null,"abstract":"<p><p>The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R. Therefore, the enthusiasm seems to be justified; but this should be followed by an attempt to obtain further insights with the goal to improve this therapy. In particular, the following issues are only partially resolved: Which mechanisms are responsible for the clinical effect following the downregulation of SOD1 protein by ASOs? Is long-term downregulation of SOD1 function associated with side effects? Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251313915"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluating neurofilament light chain serum levels as a diagnostic marker for Lyme neuroborreliosis. 评价血清神经丝轻链水平作为莱姆病的诊断指标。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-22 eCollection Date: 2025-01-01 DOI: 10.1177/17562864251314011
Cédric Hirzel, Annina Grütter, Denis Grandgirard, Robert Hoepner, Franziska Suter-Riniker, Stephen L Leib
{"title":"Evaluating neurofilament light chain serum levels as a diagnostic marker for Lyme neuroborreliosis.","authors":"Cédric Hirzel, Annina Grütter, Denis Grandgirard, Robert Hoepner, Franziska Suter-Riniker, Stephen L Leib","doi":"10.1177/17562864251314011","DOIUrl":"10.1177/17562864251314011","url":null,"abstract":"<p><strong>Background: </strong>Serum neurofilament light chain (sNfL) is a biomarker for neuro-axonal injury.</p><p><strong>Objectives: </strong>To assess sNfL's utility as a diagnostic marker for Lyme neuroborreliosis (LNB).</p><p><strong>Methods: </strong>We compared serum and CSF NfL levels in LNB patients and age-matched controls. Age-adjusted NfL values were used in receiver operating characteristic (ROC) analysis.</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Results: </strong>Eighty-six patients (30 LNB, 29 with-, and 27 without neurological disorders) were included. Compared to individuals without neurological disease, LNB patients showed increased serum (median (interquartile range, IQR): 36.3 pg/ml (19.3-112.0) vs 20 pg/ml (12.9-37.3), <i>p</i> < 0.001) and CSF NfL levels (median (IQR): 1000.0 pg/ml (286.0-6471.0) vs 182 pg/ml (99.3-474.0), <i>p</i> < 0.001). NfL concentrations were similar in LNB and other neurological disorders. ROC analysis of age-adjusted sNfL and CSF NfL levels showed areas under the curve of 0.78 (95% confidence interval (CI): 0.66-0.89) and 0.83 (95% CI: 0.71-0.94), respectively.</p><p><strong>Conclusion: </strong>sNfL concentrations lack sufficient diagnostic capability for LNB diagnosis.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251314011"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predictors and lesion patterns of dysphagia and swallowing outcomes after acute intracerebral hemorrhage. 急性脑出血后吞咽困难和吞咽结果的预测因素和病变模式。
IF 4.7 2区 医学
Therapeutic Advances in Neurological Disorders Pub Date : 2025-01-18 eCollection Date: 2025-01-01 DOI: 10.1177/17562864241311130
Xiao Hu, Min Wang, Zijie Wang, Yanfang Xie, Mengqiu Zhang, Shanyu Zhang, Tiannan Yang, Chuanqin Fang, Libo Zhao, Yanghua Tian, Qi Li
{"title":"Predictors and lesion patterns of dysphagia and swallowing outcomes after acute intracerebral hemorrhage.","authors":"Xiao Hu, Min Wang, Zijie Wang, Yanfang Xie, Mengqiu Zhang, Shanyu Zhang, Tiannan Yang, Chuanqin Fang, Libo Zhao, Yanghua Tian, Qi Li","doi":"10.1177/17562864241311130","DOIUrl":"10.1177/17562864241311130","url":null,"abstract":"<p><strong>Background: </strong>Dysphagia is a common complication following intracerebral hemorrhage (ICH) and is associated with an increased risk of aspiration pneumonia and poor outcomes.</p><p><strong>Objectives: </strong>This study aimed to explore associated lesion patterns and contributing factors of post-ICH dysphagia, and predict dysphagia outcomes following ICH.</p><p><strong>Design: </strong>A multicenter, prospective study.</p><p><strong>Methods: </strong>Patients with ICH from two stroke centers within 72 h of symptom onset received baseline bedside swallowing evaluations. Dysphagia-related lesion patterns were identified using support-vector regression-based lesion-symptom mapping. Predictors of swallowing impairment on the 7th and 30th day, as well as stroke-associated pneumonia (SAP), were determined through multiple logistic regression analyses, and nomograms were developed.</p><p><strong>Results: </strong>A total of 153 patients were included in the final analysis. Of those, 28 had dysphagia. Dysphagia-related lesions predominantly affected bilateral subcortical and adjacent cortical regions. Stroke severity, hematoma expansion, and basal ganglia hemorrhage were significantly associated with initial dysphagia. Baseline aspiration risk and age were identified as independent predictors of impaired swallowing function on days 7 and 30, and SAP. Moreover, ICH volume was significantly correlated with swallowing impairment on day 7 and SAP occurrence. Midline shift and basal ganglia hematoma remained independent predictors of impaired swallowing on day 30. Predictive models for swallowing impairment on days 7 and 30, as well as SAP, demonstrated strong calibration and discriminatory ability, with C indices of 0.867, 0.895, and 0.773, respectively.</p><p><strong>Conclusion: </strong>Post-ICH dysphagia can be predicted based on stroke severity, hematoma expansion, and basal ganglia hemorrhage. Incorporating aspiration risk and imaging evaluation can further improve the identification of patients at high risk for swallowing impairment at both 1 week and 1 month after ICH.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241311130"},"PeriodicalIF":4.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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