Therapeutic Advances in Neurological Disorders最新文献

{"title":"Paradoxical myocardial infarction risk with dual antiplatelet therapy in East Asian ischaemic stroke: a nationwide real-world cohort study and pharmacogenomic risk prediction model.","authors":"Chien-Tung Yang, Jung-Ju Lin, Paul J Chen, Wei-Lin Hsu, Der-Cherng Chen, Yu-Hsiang Lin, Chao-Hsuan Chen, Cheng-Li Lin, Hsiang-Ming Huang, XianXiu Chen","doi":"10.1177/17562864261456919","DOIUrl":"10.1177/17562864261456919","url":null,"abstract":"<p><strong>Background: </strong>Antithrombotic guidelines for secondary stroke prevention are derived predominantly from Western populations, yet East Asian patients exhibit markedly higher cytochrome P450 2C19 (CYP2C19) loss-of-function allele prevalence (50%-60% vs ~25% in Europeans) - polymorphisms essential for clopidogrel bioactivation - potentially generating population-specific cardiovascular risks not captured in Western-derived recommendations.</p><p><strong>Objectives: </strong>To characterise the 100-day cardiovascular safety and effectiveness of antithrombotic regimens in East Asian ischaemic stroke patients and to develop a pharmacogenomically informed clinical risk prediction model.</p><p><strong>Design: </strong>Nationwide retrospective cohort study.</p><p><strong>Methods: </strong>We analysed 5746 adults from Taiwan's National Health Insurance Research Database (2011-2020) stratified by antithrombotic regimen initiated within 48 h of confirmatory neuroimaging. Primary outcomes - recurrent ischaemic stroke, haemorrhagic stroke, acute myocardial infarction, heart failure and all-cause mortality - were assessed over 100 days. Multivariable Cox regression, propensity score matching, inverse probability weighting, Fine-Gray competing risks models, <i>E</i>-value bias quantification and negative control outcome analysis were applied. The East Asian Post-Stroke Antithrombotic Risk (EPSAR) score was developed incorporating age, sex, comorbidities and treatment regimen.</p><p><strong>Results: </strong>Dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) was associated with a 17.2-fold increased acute myocardial infarction risk versus aspirin monotherapy (95% confidence interval (CI) 5.61-52.7; number needed to harm 14). This signal was robust across all analytical approaches (propensity-matched hazard ratio (HR) 11.8; inverse probability of treatment weighting HR 13.4; competing-risks subdistribution HR 14.8) and yielded an <i>E</i>-value of 33.4, substantially exceeding the strength of known clinical confounders. Warfarin-containing regimens conferred markedly elevated haemorrhagic stroke risk (HR 7.11-8.77). Aspirin monotherapy demonstrated a 94% all-cause mortality reduction versus no treatment. Negative control outcomes showed no systematic bias (joint test <i>p</i> = 0.98). The EPSAR model achieved a C-statistic of 0.78 (95%CI 0.72-0.84).</p><p><strong>Conclusion: </strong>DAPT is associated with unexpected myocardial infarction risk in East Asian stroke patients, consistent with CYP2C19-mediated pharmacogenomic vulnerability. These findings challenge the universal applicability of Western-derived guidelines and support integration of pharmacogenomic risk stratification into antithrombotic prescribing for East Asian populations.</p><p><strong>Clinical trial registration: </strong>Not applicable (observational study).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261456919"},"PeriodicalIF":4.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346253","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":"Brain age gap in multiple sclerosis: associated with disability but independent of serum biomarkers.","authors":"Marc Pawlitzki, Patricia Kirschner, Lars Masanneck, Ramona Hagler, Elias Meier, Marius Vach, Hernan Inojosa, Tjalf Ziemssen, Vivien Lorena Ivan, Shammi More, Kaustubh Patil, Parnian Firouzi-Memarpuri, Julian Caspers, Jonathan Repple, Udo Dannlowski, Michael Khalil, Sven G Meuth, Christian Rubbert","doi":"10.1177/17562864261458516","DOIUrl":"10.1177/17562864261458516","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is influenced by age-related brain alterations and affects cellular aging mechanisms. Machine-learning models can estimate brain-predicted age from magnetic resonance imaging (MRI) to quantify these aging-related changes.</p><p><strong>Objectives: </strong>This study examines whether the difference between predicted and chronological age (BrainAGE) relates to clinical disability and biomarkers of neuro-axonal injury in MS.</p><p><strong>Design: </strong>This study analyzed brain-predicted age from structural 3D T1-weighted MRI in 82 patients with relapsing MS enrolled in three prospective clinical trials and 30 healthy controls.</p><p><strong>Methods: </strong>BrainAGE, calculated as MRI-predicted minus chronological age, was correlated with the Expanded Disability Status Scale (EDSS), MS Functional Composite subtests, and serum neurofilament light chain and glial fibrillary acidic protein.</p><p><strong>Results: </strong>The mean chronological age of patients and healthy controls included in this study was 39.2 and 40.9 years, respectively. Patients with MS (<i>n</i> = 82) showed a higher BrainAGE (6.48 ± 6.83 years) than controls (<i>n</i> = 30; 0.69 ± 6.5 years; <i>p</i> = 0.0002). BrainAGE increased stepwise from controls to patients with EDSS < 3 and EDSS ⩾3 (<i>p</i> < 0.0001). Higher BrainAGE correlated with worse 9-Hole Peg Test (9HPT, ρ = 0.34, <i>p</i> = 0.002) and Timed 25-Foot Walk performance (T25FW, ρ = 0.23, <i>p</i> = 0.043), but not with serum neurofilament light chain (<i>p</i> = 0.68) or glial fibrillary acidic protein (<i>p</i> = 0.33). In multivariable regression models adjusting for chronological age, sex, disease duration, and disease-modifying therapy, BrainAGE remained significantly associated with EDSS, 9HPT, and T25FW performance. sNfL and sGFAP remained nonsignificant after adjustment.</p><p><strong>Conclusion: </strong>Our findings suggest that BrainAGE and serum biomarkers capture complementary aspects of MS pathology, supporting a multimodal approach to assess disease progression.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ID: SATURATE: NCT05701423, 360PMS: NCT06501950, SAFEGUIDE-MS: NCT06461481.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261458516"},"PeriodicalIF":4.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346222","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":"Prediction of cognitive impairment in epilepsy with spike-and-wave activation in sleep based on EEG.","authors":"Rui Han, Jialing Li, Cuifang Liang, Jun Ma, Jie Luo, Bingwei Peng","doi":"10.1177/17562864261453784","DOIUrl":"10.1177/17562864261453784","url":null,"abstract":"<p><strong>Background: </strong>Spike-and-wave activation in sleep (SWAS) may lead to irreversible cognitive impairment, progressing to epileptic encephalopathy (EE)-SWAS. However, existing EEG studies have not differentiated between SWAS patients based on their future cognitive outcomes.</p><p><strong>Objectives: </strong>This study aims to extract features from the sleep EEG of SWAS patients and develop a machine learning model to predict cognitive outcomes.</p><p><strong>Design: </strong>A retrospective study.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on the sleep EEG obtained during the interictal period of 41 SWAS patients (15 with cognitive impairment). Cognitive impairment prediction models (support vector machine (SVM) and light gradient boosting machine (LightGBM)) were constructed based on spike-wave index (SWI) (the gold standard for diagnosing SWAS) and multidimensional EEG features, including functional connectivity (FC), minimum spanning tree (MST), and time-frequency-nonlinear (TFN) features, alongside a multidomain fusion (MDF) model integrating all feature sets. The performance of these EEG-based models was compared with the SWI model.</p><p><strong>Results: </strong>Models using the single SWI feature showed limited predictive capability (highest ACC: 0.756, AUC: 0.749). Conversely, multidimensional EEG models demonstrated superior performance. Specifically, the FC-based SVM model achieved the highest accuracy (0.873). Furthermore, MDF-based LightGBM models outperformed all single-feature-set models in overall discriminative capability (highest AUC: 0.934). These findings highlight the superiority of multidimensional EEG features over SWI for predicting cognitive outcomes in SWAS.</p><p><strong>Conclusion: </strong>The developed EEG-based machine learning models hold potential to assist in early cognitive prediction and treatment decisions for SWAS patients. However, given the current methodological limitations, further clinical verification is warranted.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261453784"},"PeriodicalIF":4.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346286","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":"Cladribine use for multiple sclerosis with autoimmune comorbidities: retrospective analysis of the French MS registry, case series, and therapeutic considerations.","authors":"Vito A G Ricigliano, Ines Masmoudi, Marine Boudot de la Motte, Eric Manchon, Jérôme De Seze","doi":"10.1177/17562864261458568","DOIUrl":"10.1177/17562864261458568","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune (AI) comorbidities are common in people with multiple sclerosis (MS) and may complicate therapeutic management, particularly when dual immunosuppression is required. Cladribine, an immune reconstitution therapy approved for relapsing MS, has shown potential benefit in selected autoimmune disorders.</p><p><strong>Objectives: </strong>To evaluate the prevalence of AI comorbidities in a large French MS cohort and explore the potential efficacy of cladribine in MS patients with concomitant autoimmune diseases.</p><p><strong>Design: </strong>Retrospective multicenter registry analysis combined with a descriptive case series and literature review.</p><p><strong>Data sources and methods: </strong>Data were retrospectively extracted from the European Database for MS across five French tertiary MS centers. Adults with MS and documented autoimmune comorbidities were identified, including a subgroup treated with oral cladribine. In addition, eight detailed clinical cases of MS associated with autoimmune diseases treated with cladribine were reviewed to assess outcomes on both MS and the associated autoimmune condition.</p><p><strong>Results: </strong>Among 11,410 people with MS, 901 had at least one autoimmune comorbidity, corresponding to a prevalence of 7.9 ± 0.25% (age 50.8 years), with a predominance of women. Of 385 cladribine-treated patients, 39 (10.1% ± 1.54%) had concurrent autoimmune disorders, although this proportion did not significantly differ from the overall cohort (<i>p</i> = 0.11). Eight cases involving ankylosing spondylitis (<i>n</i> = 3), psoriatic arthritis (<i>n</i> = 2), psoriasis (<i>n</i> = 1), rheumatoid arthritis (<i>n</i> = 1), and sarcoidosis (<i>n</i> = 1) were analyzed. Cladribine was consistently associated with MS stability, while efficacy on associated autoimmune conditions was variable, with more favorable outcomes observed in ankylosing spondylitis, psoriasis, and sarcoidosis.</p><p><strong>Conclusion: </strong>Autoimmune comorbidities affect approximately 8% of the French MS population and are more frequent in women. Cladribine may represent a useful therapeutic option in selected patients with concomitant autoimmune disorders, potentially limiting prolonged dual immunosuppression. Larger prospective studies are required to confirm efficacy and safety.</p><p><strong>Trial registration: </strong>OFSEP/EDMUS registry, ClinicalTrials.gov: NCT02889965.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261458568"},"PeriodicalIF":4.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319107","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":"Remote brainstem lesion associated with lower cervical spinal dural arteriovenous fistula-venous outflow bottleneck: a case report and literature review.","authors":"Yohei Takenobu, Kayoko Yukawa, Jumpei Sugiyama, Takeshi Kawauchi, Yukinori Terada, Manabu Inoue, Kenji Hashimoto","doi":"10.1177/17562864261456509","DOIUrl":"10.1177/17562864261456509","url":null,"abstract":"<p><p>Spinal dural arteriovenous fistula (SDAVF) is an important cause of venous congestive myelopathy, as timely treatment offers the potential for neurological recovery. However, it is sometimes misdiagnosed when presenting with atypical intracranial or brainstem lesions. Although venous congestion in SDAVFs typically develops adjacent to the shunting site, altered venous outflow dynamics occasionally result in remote parenchymal involvement. We present a case of lower cervical SDAVF manifesting as a remote medullary lesion mimicking area postrema syndrome. Subsequent spinal imaging and digital subtraction angiography revealed a right C6 SDAVF with cranially directed venous drainage. Fusion imaging of three-dimensional rotational angiography and anatomical MRI delineated the venous outflow bottleneck with abrupt focal narrowing at the cerebellomedullary fissure, which likely served as a morphological bottleneck contributing to preferential medullary congestion. The fistula was successfully treated via endovascular embolization, achieving complete angiographic obliteration and clinical recovery. A literature review was also conducted to characterize the clinical features and identify the common diagnostic pitfalls associated with these rare manifestations; however, the precise anatomical mechanisms for remote lesions remain elusive. This case highlights a potential anatomical mechanism wherein focal narrowing in the venous drainage pathway may predispose to atypical lesion localization. Furthermore, therapeutic considerations are discussed, emphasizing a stepwise treatment strategy in which endovascular obliteration is prioritized when the anatomy is favorable and surgical disconnection is reserved for refractory cases.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261456509"},"PeriodicalIF":4.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319110","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":"Single-channel EEG captures tDCS-induced changes in neural reactivity: a pilot study in disorders of consciousness patients and healthy controls.","authors":"Lior Molcho, Neta B Maimon, Nathan Intrator, Jeremy Barron, Efraim Jaul, Roxane S Hoyer, Steven Laureys, Oded Meiron","doi":"10.1177/17562864261456536","DOIUrl":"10.1177/17562864261456536","url":null,"abstract":"<p><strong>Background: </strong>Understanding and enhancing neural recovery in disorders of consciousness (DoC) remains a critical challenge in clinical care. Clinical scales such as the Coma Recovery Scale-Revised (CRS-R) are essential, but reflect behavioral responsiveness and may not fully capture subtle neurophysiological changes. Transcranial direct current stimulation (tDCS) has shown promise, yet objective biomarkers to assess treatment response are needed.</p><p><strong>Objectives: </strong>This proof-of-concept study explores the feasibility and sensitivity of combining a compact single-channel EEG with noninvasive brain stimulation to assess changes in neural reactivity in individuals with DoC.</p><p><strong>Design: </strong>Pilot observational study with DoC patients undergoing intervention; healthy controls were assessed to provide a physiological reference benchmark for interpreting mismatch negativity (MMN) responses and assess the specificity of EEG biomarkers relative to DoC patients.</p><p><strong>Methods: </strong>Six DoC patients underwent a 2-week open-label anodal tDCS protocol targeting the left dorsolateral prefrontal cortex. Neural activity was tracked using a compact three-electrode EEG alongside traditional 19-electrode EEG. To capture treatment-induced changes, three complementary biomarkers were analyzed: MMN, reflecting pre-attentive auditory discrimination function; Beta oscillatory activity, associated with global attentional processes; and L1, a machine-learning-derived biomarker of cognitive engagement. CRS-R, auditory event-related potentials, and EEG-based machine learning biomarkers were recorded at baseline and immediately post-intervention. Healthy controls underwent the same baseline EEG assessments without receiving stimulation.</p><p><strong>Results: </strong>MMN, Beta, and L1 demonstrated task-related modulation in healthy participants across cognitive load levels. In DoC patients, changes were observed following tDCS in MMN, Beta activity, and L1 as well, with patients demonstrating complex heterogeneous response patterns. Two patients showed behavioral improvement (CRS-R), while others exhibited increased EEG reactivity without corresponding behavioral gains.</p><p><strong>Conclusion: </strong>These findings highlight the feasibility and potential value of integrating compact EEG systems with neuromodulation protocols to monitor neural reactivity in DoC patients, with the potential to inform and refine tDCS treatment strategies over time.</p><p><strong>Trial registration: </strong>NIH Clinical Trials Registry number: NCT04614792 (https://clinicaltrials.gov/study/NCT04614792).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261456536"},"PeriodicalIF":4.0,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272960","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 heterogeneity and immunotherapy outcomes in anti-GAD65 antibody-associated autoimmune encephalitis: a retrospective study.","authors":"Yihui Qiu, Zhiheng Huang, Tengyun Ma, Lihuan Lan, Guixian Ma, Kun Nie, Yuhu Zhang, Lijuan Wang, Jiehao Zhao","doi":"10.1177/17562864261456519","DOIUrl":"10.1177/17562864261456519","url":null,"abstract":"<p><p>Anti-glutamic acid decarboxylase 65 (GAD65) antibody-associated autoimmune encephalitis (AE) is characterized by diverse neurological manifestations and systemic autoimmune comorbidities, posing diagnostic and therapeutic challenges. This study aimed to investigate the clinical heterogeneity, immunological characteristics, neuropathological features, and therapeutic outcomes in patients with anti-GAD65 AE. A retrospective study was performed in six patients with anti-GAD65 AE diagnosed at Guangdong Provincial People's Hospital. Collected data included demographic, clinical manifestations, cerebrospinal fluid (CSF) profiles, neuroimaging findings, antibody titers, immunotherapy regimens, and histopathology. Initial presentations included epilepsy (50%), hyperthyroidism (33%), and stiff-person syndrome (17%). Concurrent autoimmune diseases (type 1 diabetes, autoimmune thyroiditis, and polyendocrine syndrome) were present in half of the patients. All patients exhibited elevated anti-GAD65 antibody titers in serum and CSF. CSF analysis revealed lymphocytic pleocytosis in one patient and oligoclonal bands in four tested cases. Acute immunotherapy involving corticosteroids and intravenous immunoglobulin achieved seizure control in 83%. Maintenance therapy with mycophenolate mofetil or biologics (e.g., ofatumumab, telitacicept) elicited heterogeneous serological responses, including antibody titer rebound despite clinical stability. Notably, Case 6 represented the first reported case worldwide of AE with triple positivity (anti-GAD65, anti-GABA_ARα1, and anti-GQ1b IgG antibodies), presenting with rapidly progressive cognitive impairment, extensive parenchymal lesions, and extremely high anti-GAD65 titers, yet exhibited significant improvement post-immunotherapy. Histopathology revealed CD3⁺/CD8⁺ T-cell infiltrates in perivascular, meningeal, and parenchymal regions, accompanied by aggregates of CD20⁺ B cells, CD38⁺ plasma cells, GrB⁺ non-T cells (e.g., NK cells), and activated CD68⁺ macrophages/microglia. Anti-GAD65 AE exhibits marked clinical and immunological heterogeneity, involving both humoral and T-cell-mediated pathogenic mechanisms. Coexisting antibodies may exacerbate neuronal injury through mechanisms such as antigen unmasking and antibody-dependent cellular cytotoxicity. Persistent antibody elevation and subclinical immune activity underscore the necessity of integrating multimodal biomarkers and developing personalized treatment strategies.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261456519"},"PeriodicalIF":4.0,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253406","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":"Complement C5 inhibitors as add-on rescue treatment in severe AQP4-antibody neuromyelitis optica spectrum disorder attacks: a case series and literature review.","authors":"Kai Xin Gan, Sarah Hasnor Binti Abu Hassan, Xiu Ling Tan, Kelvin Zhenghao Li, Umapathi Thirugnanam, Tianrong Yeo","doi":"10.1177/17562864261449515","DOIUrl":"10.1177/17562864261449515","url":null,"abstract":"<p><p>Acute attacks of aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-Ab NMOSD) are typically managed with intravenous methylprednisolone, with therapeutic plasma exchange (PLEX) reserved for severe episodes. Despite these interventions, a subset of patients fails to respond and may sustain significant neurological disability. Complement C5 inhibitors, currently approved for long-term relapse prevention, have recently gained attention as a potential rescue therapy by rapidly inhibiting the terminal complement cascade, thus preventing downstream astrocytic injury. We report three patients with AQP4-Ab severe optic neuritis refractory to IV methylprednisolone and PLEX who demonstrated significant clinical improvement following administration of C5 inhibitors during the acute attack phase. Case 1 (right optic neuritis) and Case 3 (bilateral optic neuritis) received eculizumab, achieving near-complete and complete recovery of visual acuity, respectively. Both patients subsequently transitioned to rituximab within 8 weeks after their fourth weekly eculizumab infusion, while on a moderate dose of prednisolone. Case 2 (left optic neuritis) received ravulizumab, achieving partial visual recovery, and was continued on maintenance ravulizumab. Meningococcal prophylaxis with penicillin V was administered for all three patients. A literature review identified 10 publications utilising C5 inhibitors as acute attack therapies, totalling 31 cases, including our present series. Of these, 30 patients (97%) experienced neurological improvement within 4 weeks, with 28 (90%) showing improvement within the first week. Complete or near-complete recovery was observed in 42% of patients, while 55% achieved partial recovery, and one patient (3%) had no recovery. Patients achieving complete or near-complete recovery received C5 inhibitors significantly earlier than those with partial or no recovery (median 15.0 vs 24.0 days from symptom onset, <i>p</i> = 0.010); an optimal analytical cutoff of 23 days was identified. Infections were uncommon with no severe infections reported. In conclusion, emerging evidence supports the use of C5 inhibitors for acute NMOSD attacks, but larger studies are needed to establish robust evidence and inform clinical practice.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261449515"},"PeriodicalIF":4.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13219948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138823","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":"Adherence to risk minimization measures for alemtuzumab use in multiple sclerosis: a drug utilization study in four European countries.","authors":"Carmen de Keijzer, Jian-Yu E, Qian Yang, Robert Gitonga, David Hiller, Stephanie Jurgensen, Naji Salloum, Janete Cunha-Santos, Emmanuelle Hoogewys-Cynober, Laetitia Vinet, Magdalena Chirieac, Hadj Benzerdjeb, Daniela Thoene, Tjalf Ziemssen, Jiří Drahota, Dana Horáková, William Brown, Jeremy Hobart, Neil P Robertson, Katja M Hakkarainen, Sarah-Jo Sinnott","doi":"10.1177/17562864261444676","DOIUrl":"10.1177/17562864261444676","url":null,"abstract":"<p><strong>Background: </strong>The European Union Summary of Product Characteristics (EU SmPC) for alemtuzumab in multiple sclerosis (MS) was revised in January 2020 under an Article 20 EU-pharmacovigilance procedure to include a revised indication, additional contraindications, and new monitoring requirements.</p><p><strong>Objectives: </strong>To evaluate adherence to the revised SmPC for alemtuzumab across four European countries.</p><p><strong>Design: </strong>Descriptive cohort study using secondary healthcare data recorded between January 2020 (date of alemtuzumab EU SmPC revision) and the latest database update in each data source (ranging from March 2022 to January 2024).</p><p><strong>Methods: </strong>Data are used from: the Czech Republic MS registry (ReMuS), a cohort study of patients treated with alemtuzumab in Germany (long-Term study foR obsErvAtion of Treatment with alemtuzumab in active relapsing-remitting MS (TREAT-MS)), chart review data from three United Kingdom (UK) centers, and administrative healthcare data from the Belgian Social Security database (L'Agence InterMutualiste-Het InterMutualistisch Agentschap (AIM-IMA)). Adherence to revised indications, contraindications, and safety monitoring was summarized descriptively.</p><p><strong>Results: </strong>Data from 2046 people with MS treated with at least one course of alemtuzumab were assessed. Of 155 patients evaluable for adherence to the indication, 66.7% met the revised indication in ReMuS (<i>n</i> = 54/81; increasing to 75.3% after manual checks), 87.5% in TREAT-MS (<i>n</i> = 7/8), 66.7% in UK centers (<i>n</i> = 26/39; increasing to 79.5% in sensitivity analyses), and 100.0% in AIM-IMA (<i>n</i> = 22). Of 549 courses evaluated, 77.5%-97.8% were not contraindicated. While adherence to safety monitoring tests varied, heart rate and blood pressure were recorded for ⩾77.5% of courses before treatment and ⩾83.1% of courses during treatment. Platelet testing was conducted for 29.1%-51.4% of courses during treatment. Adherence to long-term (up to month 48) post-infusion monitoring was approximately 50%.</p><p><strong>Conclusion: </strong>Alemtuzumab was prescribed in accordance with the indication in 67%-88% of patients included in this study. It was prescribed in accordance with the listed contraindications in 78%-98% of courses included in the study. Adherence to the monitoring schedule is adequate to maintain the benefit-risk profile of alemtuzumab.</p><p><strong>Trial registration: </strong>This study was registered in the Heads of Medicines Agency European Medicines Agency (EMA) catalog (EUPAS42540). Results are available on the EMA website: https://catalogues.ema.europa.eu/node/3602/resources.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261444676"},"PeriodicalIF":4.0,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017385","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 neurotoxic legacy of CAR-T cells: where do we stand?","authors":"Simona Pagliuca, Caroline Jacquet, Marie Thérèse Rubio, Pierpaolo Sorrentino","doi":"10.1177/17562864261440261","DOIUrl":"10.1177/17562864261440261","url":null,"abstract":"<p><p>Chimeric antigen receptor T (CAR-T) cell therapy has transformed outcomes for relapsed/refractory B-cell malignancies and is increasingly reshaping the therapeutic landscape of autoimmune disorders and solid tumors, offering curative potential where options were previously limited. Its broader deployment is, however, constrained by immune-mediated toxicities, chiefly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS spans a heterogeneous spectrum from mild aphasia and tremor to seizures, cerebral edema, coma, and death, and remains difficult to predict prospectively. As CAR-T platforms expand beyond CD19 malignancies, neurotoxicity phenotypes are also broadening beyond classical ICANS. In plasma cell dyscrasias, BCMA-directed CAR-T has been associated with delayed non-ICANS neurotoxicities, including movement and neurocognitive/behavioral symptoms, cranial nerve palsies, and peripheral neuropathic presentations. In parallel, early experiences with CAR-T and related immune effector therapies in autoimmune and neuroimmunologic diseases suggest distinct inflammatory contexts and potentially different neurotoxicity patterns, underscoring the need for indication-specific monitoring and attribution frameworks. Converging data implicate a multilayered pathophysiology involving systemic cytokine surges, disruption of the blood-brain barrier, endothelial dysfunction, and context-dependent trafficking of activated CAR-T cells and other immune effectors into the CNS with baseline neurological vulnerability and the peri-infusion inflammatory milieu likely modulating individual risk. Given the frequency of these complications, an active research effort is underway to identify clinical, functional, and biological signals that could predict and improve their management. However, most biomarkers remain investigational, lacking prospective validation and straightforward clinical utility. This review synthesizes current evidence on the epidemiology, mechanisms, and monitoring of ICANS and emerging non-ICANS syndromes, and offers a fresh perspective on integrated, multimodal risk models to enable more precise stratification and timely intervention across indications.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261440261"},"PeriodicalIF":4.0,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975699","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}