{"title":"Comparison of outcomes and postoperative immunotherapy between patients with non-thymomatous and thymomatous myasthenia gravis following thymectomy.","authors":"Qing Zhang, XuanXuan Pan, Zhuajin Bi, Jiayang Zhan, Mengge Yang, Jing Lin, Mengcui Gui, Zhijun Li, Min Zhang, Xue Ma, Bitao Bu","doi":"10.1177/17562864251343573","DOIUrl":"10.1177/17562864251343573","url":null,"abstract":"<p><strong>Background: </strong>Outcomes after thymectomy differ greatly between non-thymomatous and thymomatous myasthenia gravis (MG), meriting an in-depth exploration.</p><p><strong>Objective: </strong>To examine the treatment and prognosis of non-thymomatous and thymomatous MG patients after thymectomy.</p><p><strong>Design: </strong>A multicenter, retrospective, case-control study focused on MG patients following thymectomy from November 2010 to January 2024. After propensity score matching, 284 patients (142 with non-thymomatous MG and 142 with thymomatous MG) were included, with a median follow-up of 2.94 years.</p><p><strong>Methods: </strong>Four outcomes were examined: minimal manifestations status (MMS) or better at the final visit, sustained clinical response, postoperative myasthenic crisis, and long-term mortality. Kaplan-Meier, logistic regression, cox regression, nomogram, receiver operating characteristic curve, decision curve, and calibration curve analyses were used for assessment.</p><p><strong>Results: </strong>Non-thymoma patients had a lower proportion of postoperative myasthenic crisis (5.6% vs 13.4%, <i>p</i> = 0.026) and long-term mortality (1.4% vs 9.9%, <i>p</i> = 0.002) but a higher proportion of sustained clinical response (66.2% vs 52.1%, <i>p</i> = 0.016) than thymoma patients. For both non-thymomatous and thymomatous MG, anti-acetylcholine receptor antibody (AChR-Ab) positivity was the independent predictor for MMS or better at the final visit (<i>p</i> = 0.048; <i>p</i> = 0.016) and sustained clinical response (<i>p</i> = 0.035; <i>p</i> = 0.037). Most severe Myasthenia Gravis Foundation of America (MGFA) classification and high-grade Masaoka histopathology were independent predictors for postoperative myasthenic crisis (<i>p</i> < 0.001; <i>p</i> = 0.010) and long-term mortality (<i>p</i> = 0.006; <i>p</i> = 0.014) for thymomatous MG. Postoperative prednisone combined with tacrolimus (Pred + TAC) was associated with achieving sustained clinical response (<i>p</i> = 0.026; <i>p</i> = 0.030) and prednisone tapering for both groups.</p><p><strong>Conclusion: </strong>Non-thymomatous MG exhibited a more benign course with better outcomes. AChR-Ab positivity indicated a better prognosis for both groups, while thymomatous MG with severe MGFA classification and high-grade histopathology requires close monitoring and follow-up. Postoperative Pred + TAC could be an effective immunotherapy option for beneficial outcomes.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251343573"},"PeriodicalIF":4.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476758","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}
Jan Kassubek, Diego Santos Garcia, Wolfgang H Jost, Lars Wojtecki, Fradique Moreira, Miguel M Fonseca, Glynn Harrison-Jones, Isabel Pijuan, Carmen Denecke Muhr
{"title":"Insights into retention and safety/tolerability of apomorphine sublingual film in patients with Parkinson's disease and OFF episodes: post hoc analyses of a phase III, open-label study.","authors":"Jan Kassubek, Diego Santos Garcia, Wolfgang H Jost, Lars Wojtecki, Fradique Moreira, Miguel M Fonseca, Glynn Harrison-Jones, Isabel Pijuan, Carmen Denecke Muhr","doi":"10.1177/17562864251343583","DOIUrl":"10.1177/17562864251343583","url":null,"abstract":"<p><strong>Background: </strong>Managing OFF episodes in patients with Parkinson's disease becomes increasingly challenging over time, making it critical to tailor treatment to each patient's needs and characteristics for effective care.</p><p><strong>Objectives: </strong>Study CTH-301 assessed the long-term safety/tolerability and efficacy of sublingual apomorphine (SL-APO) for the on-demand treatment of OFF episodes.</p><p><strong>Design: </strong>The findings from four post hoc analyses of Study CTH-301, conducted to understand factors influencing SL-APO retention and safety/tolerability, with a particular focus on oropharyngeal treatment-emergent adverse events (TEAEs) are reported.</p><p><strong>Methods: </strong>The first analysis evaluated baseline variables differing between patients who completed the study and those who discontinued due to either lack of efficacy or adverse events to help define patients more likely to benefit from SL-APO therapy: The second and third analyses compared safety/tolerability between the subgroups of patients who were or were not receiving dopamine agonist (DA) treatment, and in those aged <70 or ⩾70 years at baseline, respectively. The fourth analysis examined oropharyngeal TEAEs.</p><p><strong>Results: </strong>Patients in a younger age group, those experiencing morning akinesia or delayed ON, and those taking lower dose/fewer intakes of levodopa and concomitant DAs were more likely to benefit from SL-APO therapy. Patients taking concomitant DAs reported lower rates of DA-related TEAEs and a higher mean SL-APO optimal dose. Specific analyses in patients aged ⩾70 years indicated that this age group reported similar rates of TEAEs and a similar profile of the most common TEAEs compared with the group aged <70 years. A lower total daily dose of SL-APO was associated with a reduced risk of developing oropharyngeal TEAEs. Such events were mostly mild or moderate, occurring within the first months after SL-APO initiation, and generally resolved, with worsening being rare.</p><p><strong>Conclusion: </strong>These analyses provided insights into retention and safety/tolerability of SL-APO, helping clinicians and patients make informed treatment decisions.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251343583"},"PeriodicalIF":4.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476759","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}
Fabio Buttari, Ettore Dolcetti, Francesca Romana Rizzo, Caterina Rizzi, Gianluca Lauritano, Angela Borrelli, Federica Azzolini, Roberta Fantozzi, Francesco Assogna, Antonella Conte, Diego Centonze
{"title":"Cladribine tablets in the new multiple sclerosis era.","authors":"Fabio Buttari, Ettore Dolcetti, Francesca Romana Rizzo, Caterina Rizzi, Gianluca Lauritano, Angela Borrelli, Federica Azzolini, Roberta Fantozzi, Francesco Assogna, Antonella Conte, Diego Centonze","doi":"10.1177/17562864251342855","DOIUrl":"10.1177/17562864251342855","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune condition characterized by inflammatory demyelination that leads to irreversible neurological damage within the central nervous system (CNS). This review examines the therapeutic potential and clinical efficacy of cladribine tablets (CladT) for treating MS, focusing on the immune reconstitution mechanism and CNS effects. CladT represents a notable advance among disease-modifying therapies for MS due to its selective targeting of lymphocytes, resulting in sustained yet reversible immune modulation. This action leads to a substantial reduction in memory B cells while preserving the innate immune system and maintaining immunoglobulin levels, thereby mitigating the risks of secondary autoimmunity and infection. Cladribine appears to penetrate the blood-brain barrier, as indicated by cerebrospinal fluid (CSF) studies from parenteral cladribine use. In MS, CladT is associated with reductions in CSF immunological markers, such as oligoclonal bands and neurofilament light chain levels; it also mitigates acute and chronic inflammation, as evidenced, respectively, by consistent reductions in unique active lesions, and significant decrease in slowly expanding lesions in patients with predominant grey matter damage. These findings underscore the potential of CladT in reducing disability accumulation and improving long-term clinical outcomes in patients with highly active disease. By synthesizing data from clinical trials and real-world studies, this review underscores the effectiveness of CladT in reducing relapse rates, disability progression and magnetic resonance imaging-detected disease activity and emphasizes the importance of early high-efficacy treatment for optimizing long-term outcomes. Furthermore, emerging biomarkers are discussed as potential tools for predicting individual responses to therapy, thereby enabling more personalized treatment strategies. This review also provides valuable insights into the positive impact of CladT on quality of life measures, long-term outcomes and safety profile, all of which support the use of CladT in the evolving landscape of MS management.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251342855"},"PeriodicalIF":4.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476756","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}
Ali Hammed, Almonzer Al-Qiami, Ali Hasan, Gregor Richter, Asmaa Zakria Alnajjar, Josef Rosenbauer, Karel Kostev, Omar Ismail, Veit Braun, Christian Tanislav
{"title":"Efficacy and safety of combining re-irradiation with bevacizumab compared to bevacizumab alone in the management of recurrent high-grade gliomas: a meta-analysis and systematic review.","authors":"Ali Hammed, Almonzer Al-Qiami, Ali Hasan, Gregor Richter, Asmaa Zakria Alnajjar, Josef Rosenbauer, Karel Kostev, Omar Ismail, Veit Braun, Christian Tanislav","doi":"10.1177/17562864251343574","DOIUrl":"10.1177/17562864251343574","url":null,"abstract":"<p><strong>Background: </strong>There is currently no established standard of care for recurrent glioblastoma (GBM). Re-irradiation (re-RT) and Bevacizumab (BEV) are both used in salvage treatment, but their combined efficacy remains uncertain.</p><p><strong>Objectives: </strong>To evaluate whether combining re-irradiation with BEV improves survival outcomes compared to BEV alone in patients with recurrent high-grade gliomas (rHGG).</p><p><strong>Design: </strong>Systematic review and meta-analysis of two-arm clinical trials.</p><p><strong>Data sources and methods: </strong>A comprehensive literature search was conducted in Scopus, PubMed, Web of Science, and the Cochrane Library up to April 2024. Two independent reviewers assessed studies for eligibility and extracted data. Study quality was evaluated using the ROBINS-I and ROBINS-II tools. The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), toxicity, and prognostic factors.</p><p><strong>Results: </strong>The meta-analysis demonstrated a significant improvement in OS with combined BEV and re-irradiation compared to BEV alone (hazard ratio (HR) 0.69, 95% confidence interval (CI: 0.56-0.85); <i>p</i> = 0.0005), corresponding to a 31% reduction in the risk of death. PFS also improved significantly (HR 0.64, 95% CI (0.45-0.90); <i>p</i> = 0.01). No significant increase in grade 3 toxicities was observed with the combination therapy. Subgroup analyses indicated that younger age and female gender were statistically associated with better OS, though the effect of age was modest and male gender was linked to poorer survival. Karnofsky performance status significantly influenced survival. Pulsed versus non-pulsed re-irradiation showed no differential effect on outcomes.</p><p><strong>Conclusion: </strong>The combination of re-irradiation and BEV significantly improves both OS and PFS in patients with rHGG, without increasing severe toxicity. These findings support the safety and efficacy of the combined approach. Prospective trials are warranted to guide standardized treatment protocols.</p><p><strong>Trial registration: </strong>This review was prospectively registered with PROSPERO (CRD42023463183).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251343574"},"PeriodicalIF":4.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317903","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}
Ming-Ya Luo, Yang Qu, Peng Zhang, Reziya Abuduxukuer, Li-Juan Wang, Li-Chong Yang, Zhi-Guo Li, Xiao-Dong Liu, Ce Han, Dan Li, Wei-Jia Wang, Dian-Ping Lv, Ming Liu, Jian Gao, Jing Xu, Yongfei Jiang, Hai-Nan Chen, Fu-Jin Li, Li-Ming Sun, Qi-Dong Sun, Yingbin Qi, Si-Yin Sun, Yu Zhang, Zhen-Ni Guo, Yi Yang
{"title":"Prediction of outcomes following intravenous thrombolysis in patients with acute ischemic stroke using serum UCH-L1, S100β, and NSE: a multicenter prospective cohort study employing machine learning methods.","authors":"Ming-Ya Luo, Yang Qu, Peng Zhang, Reziya Abuduxukuer, Li-Juan Wang, Li-Chong Yang, Zhi-Guo Li, Xiao-Dong Liu, Ce Han, Dan Li, Wei-Jia Wang, Dian-Ping Lv, Ming Liu, Jian Gao, Jing Xu, Yongfei Jiang, Hai-Nan Chen, Fu-Jin Li, Li-Ming Sun, Qi-Dong Sun, Yingbin Qi, Si-Yin Sun, Yu Zhang, Zhen-Ni Guo, Yi Yang","doi":"10.1177/17562864251342429","DOIUrl":"10.1177/17562864251342429","url":null,"abstract":"<p><strong>Background: </strong>Acute ischemic stroke (AIS) is a leading cause of mortality and disability worldwide. Intravenous thrombolysis (IVT) improves recovery, but predicting outcomes remains challenging. Machine learning (ML) and biomarkers like ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein β (S100β), and neuron-specific enolase (NSE) may enhance prognostic accuracy.</p><p><strong>Objectives: </strong>We aimed to assess the predictive value of serum brain injury biomarkers for 3-month outcomes in AIS patients treated with IVT, using an ML-based model.</p><p><strong>Design: </strong>A multicenter prospective cohort study was conducted, enrolling AIS patients treated with recombinant tissue plasminogen activator from 16 hospitals.</p><p><strong>Methods: </strong>Of 1580 patients, 1028 were included and divided into training (<i>n</i> = 571), testing (<i>n</i> = 243), and external validation (<i>n</i> = 214) cohorts. Thirty-three variables, including demographics, clinical data, and biomarkers (UCH-L1, S100β, NSE), were analyzed. Least Absolute Shrinkage and Selection Operator regression was used for feature selection, and six ML algorithms were tested. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), <i>F</i>1-score, calibration curve, and decision curve analysis.</p><p><strong>Results: </strong>The light gradient boosting machines (LightGBM) model achieved the best performance in the training dataset (AUC: 0.846; <i>F</i>1-score: 0.789) and external validation dataset (AUC: 0.714). Eight critical predictors, including age, admission National Institutes of Health Stroke Scale (NIHSS) score, Trial of Org 10172 in Acute Stroke Treatment, white blood cell, finger blood glucose, UCH-L1, S100β, and NSE, were identified and incorporated into an ML model for clinical application. Shapley additive interpretation analysis enhances the interpretability of the model, with NIHSS score and NSE as top contributors. External validation confirmed good calibration and consistent net benefit across threshold probabilities (0.1-0.8).</p><p><strong>Conclusion: </strong>Integrating serum biomarkers (UCH-L1, S100β, NSE) with ML significantly improves 3-month outcome prediction in AIS patients. The LightGBM model offers robust performance and clinical interpretability for individualized treatment planning.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251342429"},"PeriodicalIF":4.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286572","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}
Jessica Ailani, Nemin Chen, Avani Patel, Nathan Spence, Nikoletta Sternbach, Katie B Tellor, Motomori Lewis, Joshua Brown
{"title":"Measuring incremental burdens associated with increasing preventive-treatment failures among adults with migraine: a retrospective, cross-sectional study.","authors":"Jessica Ailani, Nemin Chen, Avani Patel, Nathan Spence, Nikoletta Sternbach, Katie B Tellor, Motomori Lewis, Joshua Brown","doi":"10.1177/17562864251337431","DOIUrl":"10.1177/17562864251337431","url":null,"abstract":"<p><strong>Background: </strong>Migraine inflicts substantial personal, social, and economic tolls on many adults in the United States (US). Acute and preventive medicines can offer some relief, but most patients are untreated or experience treatment failures. How preventive-treatment failures affect outcomes for patients no longer on preventive treatments or for patients with migraine is insufficiently understood.</p><p><strong>Objective: </strong>To measure the patient-reported health and economic burdens associated with increasing preventive-treatment failures among US adults with diagnosed migraine.</p><p><strong>Design: </strong>Retrospective, cross-sectional study.</p><p><strong>Methods: </strong>Data analyzed were from the 2023 US National Health and Wellness Survey. Participants were adults diagnosed with migraine, having ≥4 monthly migraine or headache days, having taken acute or preventive prescription migraine medications or currently taking acute prescription migraine medications, and taking no preventive migraine medications. Participants were categorized as never treated with preventive medicines, having failed 1 preventive medicine, or having failed ≥2 preventive medicines. Health-related quality of life (HRQoL) was assessed with the Migraine Disability Assessment, RAND's 36-Item Short Form Survey Instrument, 5-Level EuroQoL instrument (EQ-5D), Work Productivity and Activity Impairment General Health version, 9-Item Patient Health Questionnaire, and 7-Item Generalized Anxiety Disorder scale. Details about medication use and health care resource use (HCRU) were collected. Data were adjusted by inverse probability of treatment weighting and compared using two-sided two-sample <i>t</i>-tests or Chi-square tests.</p><p><strong>Results: </strong>Patients who had failed preventive treatments had poorer HRQoL, greater work productivity loss, greater nonwork activity impairment, and greater HCRU than patients who had never taken preventive treatments. The number of preventive-treatment failures scaled with disease burden. Patients with ≥2 treatment failures had significantly lower EQ-5D scores (0.69 vs 0.73) than those for prevention-naïve patients; patients with ≥2 treatment failures had significantly higher overall work productivity loss (45.9% vs 34.9%), activity impairment (46.8% vs 36.7%), and higher rates of emergency room visits (37.0% vs 25.2%), hospitalization (23.5% vs 12.3%), and neurologist visits (17.6 vs 10.9%) than those of prevention-naïve patients. Medication overuse rates were similar among patients with any treatment failures and prevention-naïve patients (migraine-specific: 34.4%-39.3%; overall: 59.2%-62.3%).</p><p><strong>Conclusion: </strong>US adults with frequent migraines who failed preventive treatments have significantly greater unmet needs and different acute medication use patterns than adults who never took treatments.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251337431"},"PeriodicalIF":4.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259001","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}
{"title":"Decoding crosstalk between neurotransmitters and α-synuclein in Parkinson's disease: pathogenesis and therapeutic implications.","authors":"Lihua Guan, Liling Lin, Chaochao Ma, Ling Qiu","doi":"10.1177/17562864251339895","DOIUrl":"10.1177/17562864251339895","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by progressive worsening of motor symptoms. The primary pathological hallmark of PD is the degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are primarily composed of α-synuclein (α-syn) aggregates. Both α-syn and various neurotransmitters, including catecholamines (catechols), play crucial roles in the pathogenesis of PD, although the precise pathogenic mechanisms remain incompletely understood. The crosstalk between neurotransmitters and α-syn is intricate and multifaceted. Pathological α-syn disrupted neurotransmitters' homeostasis by impairing release and reuptake of neurotransmitters, with specific modulation of catecholaminergic and glutamatergic systems. Conversely, neurotransmitters, especially catechols, covalently modify α-syn. Such modifications significantly influence α-syn aggregation dynamics and alter its neurotoxic properties. However, determining whether these interactions induce synergistic toxicity or confer neuroprotection remains controversial. Emerging evidence suggests other neurotransmitters like serotonin and γ-aminobutyric acid may also modulate α-syn aggregation and PD progression, though their roles require further investigation. Understanding these interactions is crucial for developing novel diagnostic and multi-target therapeutic strategies.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251339895"},"PeriodicalIF":4.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249711","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}
Sofia Marini, Silvia Falso, Federico Habetswallner, Martina Marini, Raffaele Iorio
{"title":"Complement inhibitor therapy as a steroid-sparing strategy in generalized myasthenia gravis.","authors":"Sofia Marini, Silvia Falso, Federico Habetswallner, Martina Marini, Raffaele Iorio","doi":"10.1177/17562864251332037","DOIUrl":"10.1177/17562864251332037","url":null,"abstract":"<p><strong>Background: </strong>Standard management of generalized myasthenia gravis associated with anti-acetylcholine receptor autoantibodies (AChR-gMG) includes corticosteroids and nonsteroidal immunosuppressants. Complement inhibitors (CI) represent a more tailored therapeutic strategy. Real-world data on the steroid-sparing efficacy of CI remain limited.</p><p><strong>Objective: </strong>To investigate the steroid-sparing efficacy of CI in AChR-gMG.</p><p><strong>Design: </strong>We identified 69 AChR-gMG patients on corticosteroids treated with azathioprine (AZA), mycophenolate mofetil (MMF), or CI.</p><p><strong>Methods: </strong>Steroid tapering was assessed by comparing corticosteroid dosage at several time-points to baseline.</p><p><strong>Results: </strong>Steroids reductions were statistically significant for all therapies at every time point compared to baseline (all <i>p</i> < 0.001). Pairwise comparisons using the Mann-Whitney <i>U</i> test revealed significant differences between CI and MMF at 3 months (<i>p</i> = 0.0372), 6 months (<i>p</i> = 0.0193), and 9 months (<i>p</i> = 0.0321) and between CI and AZA at 6 months (<i>p</i> = 0.0415).</p><p><strong>Conclusion: </strong>CI rapidly and effectively reduced corticosteroid dosage in most AChR-gMG patients, suggesting their potential role as steroid-sparing therapeutic options.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251332037"},"PeriodicalIF":4.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200077","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}
Jon Rodríguez-Antigüedad, Gonzalo Olmedo-Saura, Javier Pagonabarraga, Saül Martínez-Horta, Jaime Kulisevsky
{"title":"Approaches for treating neuropsychiatric symptoms in Parkinson's disease: a narrative review.","authors":"Jon Rodríguez-Antigüedad, Gonzalo Olmedo-Saura, Javier Pagonabarraga, Saül Martínez-Horta, Jaime Kulisevsky","doi":"10.1177/17562864251336903","DOIUrl":"10.1177/17562864251336903","url":null,"abstract":"<p><p>Neuropsychiatric symptoms in Parkinson's disease (PD) are highly prevalent and profoundly disabling, often emerging even before the onset of motor symptoms. As the disease progresses, these symptoms usually become increasingly impairing and are now recognized as having the greatest impact on quality of life not only for patients but also for caregivers. In recent years, there have been significant advances in the diagnosis and management of neuropsychiatric symptoms. However, there are still substantial gaps in therapeutic approaches and algorithms, with limited pharmacological and nonpharmacological treatment options currently available. One of the main reasons for this is the complex molecular and neural bases of these symptoms, which involve both dopaminergic and nondopaminergic neurotransmission systems and extend far beyond the nigrostriatal pathway. As a result, the drugs currently recommended for treating neuropsychiatric symptoms in PD are few and supported by limited evidence. In this context, the experience of the treating neurologist remains critical in selecting the most appropriate individualized therapy. The aim of this paper is to review the available therapeutic options and provide an overview of current research efforts, particularly those focusing on pharmacological treatments.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251336903"},"PeriodicalIF":4.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161122","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}
Maria-Ioanna Stefanou, Aikaterini Theodorou, Annerose Mengel, Konstantinos Melanis, Christos Bakirtzis, Vasileios Giannopapas, Dimitrios K Kitsos, Markus Kowarik, Katharina Feil, Dimitrios Tzanetakos, Vasiliki Zouvelou, Elizabeth Andreadou, John S Tzartos, Sotirios Giannopoulos, Georgios Tsivgoulis
{"title":"Risk of stroke under disease modifying therapies for multiple sclerosis: a systematic review.","authors":"Maria-Ioanna Stefanou, Aikaterini Theodorou, Annerose Mengel, Konstantinos Melanis, Christos Bakirtzis, Vasileios Giannopapas, Dimitrios K Kitsos, Markus Kowarik, Katharina Feil, Dimitrios Tzanetakos, Vasiliki Zouvelou, Elizabeth Andreadou, John S Tzartos, Sotirios Giannopoulos, Georgios Tsivgoulis","doi":"10.1177/17562864251321669","DOIUrl":"10.1177/17562864251321669","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological research indicates a heightened incidence of cerebrovascular disorders among patients with multiple sclerosis (MS).</p><p><strong>Objectives: </strong>The aim of the present systematic review was to investigate the potential association between disease modifying therapies (DMTs) and the risk of stroke in MS patient populations.</p><p><strong>Data sources and methods: </strong>A systematic literature search was performed in MEDLINE and SCOPUS databases up to April 6, 2024, to identify randomized-controlled clinical trials (RCT), registry-based and cohort-studies, case-series, and case-reports reporting on acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) in MS patients under different DMTs.</p><p><strong>Results: </strong>Twenty-one studies were included: 1 RCT, 6 registry-based or cohort studies, 2 case-series and 11 case-reports. Overall, DMTs appear to reduce the risk of stroke in MS patients, with DMT exposure linked to a 50% reduction of the risk of stroke compared to no DMT exposure. Although glatiramer acetate and dimethyl fumarate appear to lower the risk of stroke, concerns about fingolimod exists due to an observed elevated risk for ischemic heart disease and hypertension. Despite the absence of detected safety concerns with alemtuzumab at the MS population level, alemtuzumab-related complications, although rare, signal the need for heightened clinical vigilance. Similarly, β-interferons have been linked to life-threatening adverse events, comprising thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). No associations between the risk of stroke and other DMTs, comprising natalizumab and teriflunomide, were detected; yet, newly approved DMTs were underrepresented.</p><p><strong>Conclusion: </strong>These findings highlight the importance of personalizing DMT selection and monitoring cardiovascular risk factors to reduce stroke risk in patients with MS.</p><p><strong>Trial registration: </strong>PROSPERO CRD42024534470.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251321669"},"PeriodicalIF":4.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12099087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143578","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}