Therapeutic Advances in Neurological Disorders最新文献

{"title":"The evolving treatment landscape of restless legs syndrome.","authors":"Maria P Mogavero, Giuseppe Lanza, Pasquale Tondo, Oliviero Bruni, Raffaele Ferri","doi":"10.1177/17562864261469017","DOIUrl":"10.1177/17562864261469017","url":null,"abstract":"<p><p>Restless legs syndrome (RLS) is a chronic sensorimotor disorder with a substantial impact on sleep, quality of life, and long-term neurological health. Because RLS has long required longitudinal clinical management in many patients, the major recent change is not the recognition of chronicity itself, but the reordering of treatment priorities as long-term evidence and clinical experience have clarified the risks of dopaminergic augmentation. This review synthesizes the progression of treatment paradigms from 2015 to 2026, focusing on how increasing recognition of augmentation has reshaped clinical decision-making. Historically, dopaminergic agents dominated RLS treatment because of robust short-term efficacy; however, their long-term risk-benefit profile has been reconsidered as augmentation became recognized as a major treatment-related complication. This led to a rebalancing of treatment strategies, with greater emphasis on iron metabolism and non-dopaminergic therapies. Iron deficiency is now considered a core pathophysiological and therapeutic target, with both oral and intravenous supplementation playing a key role even in the absence of overt anemia. Contemporary guidelines, culminating in the 2025 American Academy of Sleep Medicine recommendations, formalize this shift by endorsing α2δ ligands (gabapentin, pregabalin, and gabapentin enacarbil) and intravenous iron as first-line treatments, while discouraging routine use of dopamine agonists due to long-term risks. The modern approach is therefore augmentation-aware, iron-conscious, and phenotype-oriented, incorporating structured pathways for refractory disease that may include opioids and emerging non-dopaminergic or device-based therapies. Despite these advances, however, important gaps remain, including limited evidence for augmentation management, lack of disease-specific pharmacotherapies, and insufficient data in special populations such as children and pregnant individuals. Future directions will likely depend on mechanism-based drug development, improved biomarkers, and precision medicine approaches. Overall, the evolution of RLS treatment reflects a broader transition toward sustainable, individualized care in chronic neurological disorders.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261469017"},"PeriodicalIF":4.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631423","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":"Real-world data on the prevalence and therapy of symptomatic bladder dysfunction in people with multiple sclerosis.","authors":"Mathia Kirstein, Niklas Frahm, David Ellenberger, Alexander Stahmann, Firas Fneish, Melanie Peters, Friedemann Paul, Clemens Warnke, Kerstin Hellwig, Peter Flachenecker, Klaus Berger, Michaela Mai, Michael Hecker, Uwe K Zettl","doi":"10.1177/17562864261456559","DOIUrl":"10.1177/17562864261456559","url":null,"abstract":"<p><strong>Background: </strong>Bladder dysfunctions (BL-D) are common in people with multiple sclerosis (pwMS), significantly affecting daily life, infection risk, and survival. Nonetheless, BL-D are frequently stigmatized and inadequately addressed in clinical practice. To date, no comprehensive analysis of BL-D has been conducted in Germany.</p><p><strong>Objective: </strong>To assess the prevalence of BL-D and its subtypes in a German cohort and identify associated factors and treatment patterns.</p><p><strong>Methods: </strong>Data were analyzed from individuals enrolled in the German MS Register, aged ⩾18 with definite MS. Inclusion required ⩾3 visits and complete data on MS onset, diagnosis date, and BL-D status. BL-D were subclassified into urinary urgency, voiding dysfunction, bladder incontinence, and other BL-D. PwMS with different subtypes were compared regarding clinical, sociodemographic, and therapeutic characteristics and associated factors were identified using logistic regression.</p><p><strong>Results: </strong>The study cohort included 10,572 pwMS (71.7% female) with a mean age of 48.2 years, disease duration of 16.0 years, and median Expanded Disability Status Scale score of 2.0. BL-D was present in 38.0% of pwMS, with urinary urgency being the leading subtype (41.0%). Associations included older age, longer disease duration, progressive disease course, polysymptomatic onset, and receiving disease-modifying therapy. Interestingly, 37.1% of pwMS with BL-D received no bladder treatment, while 36.9% received pharmaceutical and 36.4% non-pharmaceutical bladder treatment.</p><p><strong>Conclusion: </strong>The results highlight the clinical relevance and burden of BL-D in MS and provide first insights into subtype-specific differences in the German MS population. Providing appropriate BL-D care requires investigation into causal factors and a deeper understanding of the underlying reasons of the treatment gap.</p><p><strong>Design: </strong>Retrospective, cross-sectional study.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261456559"},"PeriodicalIF":4.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593214","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":"Real-world implementation of continuous subcutaneous foslevodopa/foscarbidopa in advanced Parkinson's disease: first clinical experience from the Middle East.","authors":"Shivam Om Mittal, Kiran Waqar, Emma De Freitas, Yasmin Abdelmajid, Arshiya Anjum, Leanne Brown, Moncy Thomas","doi":"10.1177/17562864261464300","DOIUrl":"10.1177/17562864261464300","url":null,"abstract":"<p><strong>Background: </strong>Continuous subcutaneous foslevodopa/foscarbidopa (FLD/FCD) is the first 24-h levodopa-based subcutaneous infusion therapy for advanced Parkinson's disease (PD). Real-world data from the Middle East region are absent.</p><p><strong>Objectives: </strong>To report the first Middle Eastern clinical experience with foslevodopa/foscarbidopa, evaluating motor and non-motor outcomes, safety profile, and treatment continuation rates in routine clinical practice.</p><p><strong>Design: </strong>Retrospective, single-center, observational cohort study.</p><p><strong>Methods: </strong>Twenty-eight consecutive patients with advanced PD underwent inpatient foslevodopa/foscarbidopa initiation between January 2025 and January 2026 at a quaternary academic medical center in Abu Dhabi, United Arab Emirates. Primary outcomes were Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, daily OFF/ON hours, and Hoehn and Yahr stage; secondary outcomes included Non-Motor Symptoms Scale (NMSS) total and domain scores and MDS-UPDRS Parts I and II. Motor assessments were conducted in the practically defined OFF state at baseline and in the ON state at follow-up on stable foslevodopa/foscarbidopa therapy. Safety was assessed by systematic recording of adverse events. Paired comparisons used Wilcoxon signed-rank tests.</p><p><strong>Results: </strong>Mean age was 61.3 ± 13.5 years; disease duration 10.1 ± 7.4 years; baseline levodopa equivalent daily dose 1018 ± 574 mg. MDS-UPDRS Part III improved from 50.7 ± 14.5 (OFF-state baseline) to 27.1 ± 13.6 (ON-state follow-up; change -23.6 ± 8.3, <i>p</i> < 0.0001), representing elimination of wearing-off disability. Daily OFF time fell from 2.8 ± 1.4 to 0.9 ± 0.6 h (-1.9 ± 1.4 h; <i>p</i> < 0.0001), and good ON time increased by 2.0 ± 1.3 h (<i>p</i> < 0.0001). Hoehn and Yahr stage improved from median 3 (interquartile range (IQR) 3-4) to 2 (IQR 2-3; <i>p</i> < 0.0001). Non-motor symptom burden decreased substantially: MDS-UPDRS Parts I and II fell by 22.7 ± 9.3 points (<i>p</i> = 0.001) and NMSS total score by 29.7 ± 18.7 points (~49% reduction; <i>p</i> = 0.0007). Infusion site reactions occurred in 22 patients (79%) but were generally manageable. Six patients (21%) discontinued therapy (median 4.8 months), primarily because of skin reactions or compliance difficulties.</p><p><strong>Conclusion: </strong>Foslevodopa/foscarbidopa produced clinically meaningful improvements in motor fluctuations and non-motor symptom burden in this first Middle Eastern real-world cohort, supporting its role as an effective and feasible non-surgical device-aided therapy for advanced PD.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261464300"},"PeriodicalIF":4.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472946","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":"The conundrum of alpha-synuclein antibody failures in Parkinson's disease: a narrative review of mechanisms and alternative metabolic hypotheses.","authors":"Anastasia Bougea","doi":"10.1177/17562864261465665","DOIUrl":"10.1177/17562864261465665","url":null,"abstract":"<p><p>Parkinson's disease (PD) remains the second most common neurodegenerative disorder globally, yet disease-modifying therapies remain elusive. The past decade of therapeutic development has been dominated by the hypothesis that alpha-synuclein aggregates spread in a prion-like manner. This catalysed the development of immunotherapy approaches targeting extracellular alpha-synuclein. However, high-profile Phase II and III clinical trials, such as those for cinpanemab and prasinezumab, failed to demonstrate clinical efficacy. This narrative review evaluates alpha-synuclein-targeted immunotherapies, their mechanistic rationale, the underlying reasons for recent clinical trial failures and to propose alternative metabolic frameworks. A literature search of peer-reviewed articles published up to 10 December 2025 was performed using the PubMed database to evaluate immunotherapies, mechanistic models and trial failures in PD. The prevailing 'prion-like' spread hypothesis may be overemphasised in the context of human disease. We propose the 'Single-Neuron Degeneration Hypothesis', suggesting that PD pathology is primarily driven by intracellular autotoxicity - specifically involving the dopamine metabolite aminochrome, mitochondrial dysfunction and oxidative stress - occurring independently within each dopaminergic neuron. Multifactorial contributors to trial failure include the inadequacy of preclinical models such as MPTP, the insensitivity of the MDS-UPDRS, diagnostic heterogeneity and the statistical reality of neuronal loss rates. Future therapeutic strategies must integrate intracellular neuroprotection alongside extracellular clearance approaches, with significantly earlier intervention.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261465665"},"PeriodicalIF":4.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456753","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":"Optimizing the diagnostic timing for drug-resistant epilepsy: balancing timeliness and stability with an antiseizure medication waiting period.","authors":"Nan Li, Yanyan Chen, Guangjian Li, Jing Li, Weihong Lin","doi":"10.1177/17562864261464160","DOIUrl":"10.1177/17562864261464160","url":null,"abstract":"<p><strong>Background: </strong>While drug-resistant epilepsy (DRE) is defined by the failure of two antiseizure medications (ASM), the optimal duration to confirm such resistance remains controversial. Clinical delays intended for treatment optimization may postpone life-changing nonpharmacological interventions and increase risks associated with uncontrolled seizures, highlighting the need for standardized diagnostic timing.</p><p><strong>Objective: </strong>We aimed to identify the optimal waiting period that balances the consistency, stability, and timeliness of DRE diagnosis.</p><p><strong>Design: </strong>Retrospective observational cohort study.</p><p><strong>Methods: </strong>This study evaluated a modified DRE definition featuring a structured \"ASM waiting period\" against the original criteria. Outpatients with epilepsy received initial ASM at a tertiary center in a self-paired diagnostic simulation design. A B-spline linear model verified the inflection point at which the DRE revision proportion plateaued. A trade-off score for DRE (TOS_DRE) was developed to identify the optimal waiting period by balancing diagnostic stability and delay.</p><p><strong>Results: </strong>This study included 1573 patients. We used 28-, 219-, and 364-days as waiting periods for the analyses. The diagnostic consistency with the original standard was high (κ ⩾ 0.879, <i>p</i> < 0.001). A significant increase in diagnostic delay was observed across waiting periods (<i>p</i> < 0.001), except for the 0- and 28-day strategies (<i>p</i> = 0.290). Kaplan-Meier analysis, truncated on day 540, revealed higher DRE maintenance possibility for the 219- (hazard ratio (HR) = 0.29, 95% confidence interval (CI) 0.10-0.87, <i>p</i> = 0.028), and 364-day criteria (HR = 0.33, 95% CI 0.11-0.98, <i>p</i> = 0.046) than those for the 0-day criterion. The TOS_DRE indicated a 219-day optimal waiting period for diagnostic accuracy (<i>w</i> ₁ = 0.7). Subgroup analyses confirmed the robustness of the 219-day strategy in most scenarios.</p><p><strong>Conclusion: </strong>We propose a 219-day waiting period to operationalize an \"adequate trial\" of DRE. This timeframe may inform DRE diagnosis and evaluation of nonpharmacological therapy.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261464160"},"PeriodicalIF":4.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13338548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405882","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":"New frontiers in acute reperfusion therapy for ischaemic stroke: from recanalisation to selection, delivery and safety.","authors":"Lina Palaiodimou, Georgios Tsivgoulis","doi":"10.1177/17562864261463668","DOIUrl":"10.1177/17562864261463668","url":null,"abstract":"","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261463668"},"PeriodicalIF":4.0,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13333051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391809","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":"Narcolepsy with co-occurring epilepsy: diagnostic pitfalls and management strategy.","authors":"Xinyan Zhang, Mengling Zha, Jiafeng Ren, Jiani Chen, Dong Zhou, Josemir W Sander, Jinmei Li, Junying Zhou","doi":"10.1177/17562864261453762","DOIUrl":"10.1177/17562864261453762","url":null,"abstract":"<p><p>Narcolepsy and epilepsy are chronic neurological disorders that occasionally coexist. Overlapping symptoms, such as sudden loss of muscle tone and uncertainty regarding preservation of awareness, frequently complicate accurate diagnosis and ambiguity remains regarding optimal therapeutic strategies. To characterise the clinical features and treatment outcomes in individuals with comorbid narcolepsy and epilepsy, we described a 17-year-old girl with concomitant epilepsy and narcolepsy presented in our clinic. The overlapping symptomatology of narcolepsy and epilepsy can lead to significant diagnostic pitfalls, particularly when excessive daytime sleepiness is overlooked or attributed to external factors such as mental disorder or the side effects of antiseizure medications. Careful evaluation of clinical features, sleep studies and immunological markers through a multidisciplinary team approach is essential for accurate differentiation and optimal treatment. Prompted by this encounter, we additionally conducted a literature review and then synthesised ten reported cases of narcolepsy-epilepsy comorbidity, focusing on demographic profiles, diagnostic findings, treatment approaches and therapeutic outcomes. All ten published cases were diagnosed with narcolepsy type 1, predominantly with childhood or adolescent onset. EEG commonly showed 3-5 Hz generalised spike-and-wave discharges, and most individuals reported carrying the HLA-DQB1*06:02 allele. In more than 80% of cases, narcolepsy preceded or coincided with epilepsy, though diagnostic delays for narcolepsy were frequent. Both conditions generally responded well to combined standard treatments, such as pitolisant, sodium oxybate, lamotrigine and valproate, though antiseizure medications occasionally worsened sleepiness. This study underscores the diagnostic pitfalls associated to overlapping symptoms of narcolepsy and epilepsy and emphasises the value of multidisciplinary diagnostic collaboration for the timely recognition and effective management of these coexisting neurological disorders.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261453762"},"PeriodicalIF":4.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369628","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":"Clinical, imaging, and immunotherapeutic features in MOGAD: a retrospective real-world cohort in Northern China.","authors":"Xuetao Cao, Danqing Qin, Chunjuan Wang, Baojie Wang, Yuxiu Xiao, Xujun Chu, Shougang Guo","doi":"10.1177/17562864261458528","DOIUrl":"10.1177/17562864261458528","url":null,"abstract":"<p><strong>Background: </strong>Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a clinically heterogeneous demyelinating disorder. Current knowledge of its phenotypic spectrum and optimal treatment strategies, especially in Asian populations, remains limited.</p><p><strong>Objectives: </strong>This study aimed to characterize the clinical and imaging features of MOGAD in a Northern Chinese cohort and to evaluate the therapeutic effects of the anti-CD20 monoclonal antibody ofatumumab.</p><p><strong>Design: </strong>A retrospective study in a single center.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 108 patients who tested positive for MOG antibodies between June 2018 and August 2025, ultimately diagnosing 56 patients with MOGAD comprising 17 pediatric and 39 adult cases. Clinical, imaging, and cerebrospinal fluid (CSF) data were systematically reviewed. Ten patients received ofatumumab treatment for relapse prevention. The study was approved by the Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong First Medical University (SWYX: NO.2025-709) and written consent was obtained from all participants.</p><p><strong>Results: </strong>Cortical encephalitis was the most frequent phenotype (41.1%, 23/56), followed by Unifocal Demyelination (39.3%, 22/56). Radiographically, 94.4% of patients exhibited 1-3 lesions, predominantly in cortical regions. CSF analysis revealed elevated cell counts and protein levels, with significant variation across phenotypes (<i>p</i> < 0.05). Adults with relapsing courses experienced greater disability progression (<i>p</i> = 0.006). Ofatumumab treatment resulted in no observed relapses, along with improvements in Expanded Disability Status Scale (EDSS) and modified Rankin Scale (mRS) scores and reduction in MRI lesion burden compared with baseline (all <i>p</i> < 0.05). Notably, 50% (5/10) of ofatumumab-treated patients discontinued glucocorticoids within 12 months, compared with 19.6% (9/46) in the conventional therapy group (<i>p</i> = 0.017).</p><p><strong>Conclusion: </strong>This study delineates a distinct clinical-radiological profile of MOGAD in Northern China, characterized by a high frequency of cortical encephalitis. Furthermore, it provides preliminary evidence that ofatumumab may be a potential steroid-sparing therapeutic option for MOGAD.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261458528"},"PeriodicalIF":4.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370089","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":"Long-term use of rozanolixizumab in generalised myasthenia gravis: final pooled analysis of the phase III MycarinG study and two open-label extensions.","authors":"Vera Bril, Artur Drużdż, Julian Grosskreutz, Ali A Habib, Renato Mantegazza, Sabrina Sacconi, Kimiaki Utsugisawa, Tuan Vu, Marion Boehnlein, Fiona Grimson, Niamh Houston, Virginie Kerbusch, Irene Pulido-Valdeolivas, Thaïs Tarancón, John Vissing","doi":"10.1177/17562864261458532","DOIUrl":"10.1177/17562864261458532","url":null,"abstract":"<p><strong>Background: </strong>Myasthenia gravis (MG) is a rare autoimmune disease characterised by fluctuating and fatigable muscle weakness. In the randomised, double-blind phase III MycarinG study, one 6-week rozanolixizumab cycle significantly improved MG-specific outcomes versus placebo and was generally well tolerated in patients with generalised MG (gMG).</p><p><strong>Objectives: </strong>To assess the efficacy and safety of cyclic rozanolixizumab treatment.</p><p><strong>Design: </strong>A pooled analysis of the MycarinG, MG0004 and MG0007 studies.</p><p><strong>Methods: </strong>Following MycarinG, eligible patients could enrol in the open-label extension studies MG0004 or MG0007 to receive rozanolixizumab 7 or 10 mg/kg. In MG0004, patients received chronic weekly treatment for ⩽52 weeks. In MG0007, after an initial 6-week treatment cycle, subsequent cycles were based on symptom worsening (investigator's discretion). Final efficacy data were pooled across MycarinG, MG0004 (first 6 weeks) and MG0007 for patients receiving ⩾2 symptom-driven cycles. Efficacy endpoints included change from baseline (CFB) in MG Activities of Daily Living (MG-ADL), MG Composite (MGC) and Quantitative MG (QMG) scores. Safety outcomes were assessed in patients who received ⩾1 cycle with a ⩽8-week follow-up period across MycarinG and MG0007.</p><p><strong>Results: </strong>Overall, 188 patients received ⩾1 cycle and 129 received ⩾2 symptom-driven cycles. Across Cycles 1-13, mean (standard deviation) CFB to Day 43 in MG-ADL score ranged from -3.2 (3.3 (<i>n</i> = 113; Cycle 3)) to -6.0 (3.9 (<i>n</i> = 24; Cycle 12)). Consistent improvements in MGC and QMG scores were also observed across repeated cycles. Treatment-emergent adverse events (TEAEs) were experienced by 175/188 (93.1%) patients; most mild or moderate. Incidence remained stable with repeated cyclic treatment among patients who remained in the study at each cycle. The most common TEAE was headache (<i>n</i> = 94/188 (50.0%)).</p><p><strong>Conclusion: </strong>Repeated rozanolixizumab treatment cycles demonstrated consistent, clinically meaningful improvements in MG-specific outcomes as early as 1 week after the first infusion. Rozanolixizumab was generally well tolerated with an acceptable safety profile, supporting its long-term use as a treatment option for adults with gMG.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT03971422; NCT04124965; NCT04650854.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261458532"},"PeriodicalIF":4.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369017","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":"Residual early neurological deterioration following dual antiplatelet in stroke: post hoc analysis of the ATAMIS trial.","authors":"Yu Cui, Xiang-Ru Kong, Jing Zhang, Hui-Sheng Chen","doi":"10.1177/17562864261461421","DOIUrl":"10.1177/17562864261461421","url":null,"abstract":"<p><strong>Background: </strong>A clinically significant proportion of patients experience early neurological deterioration (END) despite receiving dual antiplatelet therapy (DAPT) for acute ischemic stroke. It is crucial to identify this specific population for risk stratification and targeted intervention.</p><p><strong>Objectives: </strong>To identify predictors for END after DAPT in acute ischemic stroke.</p><p><strong>Design: </strong>We performed a post hoc analysis of the antiplatelet therapy in acute mild to moderate ischemic stroke (ATAMIS) trial.</p><p><strong>Methods: </strong>Patients who received DAPT (clopidogrel plus aspirin) in the ATAMIS trial were included, and classified into END and Non-END groups according to whether they experienced END. END was defined as an increase of ⩾2 points within 7 days from baseline on the National Institutes of Health Stroke Scale (NIHSS). Independent predictors were identified using multivariable logistic regression.</p><p><strong>Results: </strong>Of the 1,122 patients with acute mild-to-moderate ischemic stroke treated with DAPT, 66 (5.9%) developed END within 7 days. Multivariable analysis identified three independent factors associated with increased END risk: a shorter time from symptom onset to antiplatelet initiation (adjusted odds ratio [aOR] per hour, 0.97; 95% CI, 0.95-0.99; <i>p</i> = 0.01), higher admission systolic blood pressure (aOR per mmHg, 1.01; 95% CI, 1.00-1.02; <i>p</i> = 0.047), and a stroke etiology of either small artery occlusion (aOR, 2.24; 95% CI, 1.29-3.89; <i>p</i> = 0.004) or cardioembolism (aOR, 28.36; 95% CI, 1.23-654.11; <i>p</i> = 0.04).</p><p><strong>Conclusion: </strong>Among patients with mild-to-moderate ischemic stroke receiving DAPT, key predictors of END include very early presentation, elevated systolic blood pressure at admission, and a nonlarge artery atherosclerosis etiology (small artery occlusion or cardioembolism). These findings highlight subgroups that may require intensified monitoring or adjunctive therapeutic strategies beyond standard DAPT.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT02869009.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261461421"},"PeriodicalIF":4.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346258","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}