Annals of Clinical and Translational Neurology最新文献

{"title":"SYHA1813, A VEGFR and CSF1R Inhibitor, in Patients With Recurrent High-Grade Gliomas: A Multicenter, Open-Label Phase I Study.","authors":"Zhuang Kang, Shenglan Li, Liang Wang, Qianxue Chen, Weiguo Hu, Ting Lei, Ying Mao, Jing Zhang, Xiaojun Xiang, Qiming Wang, Zhengwen He, Tao Sun, Yulei Wang, Mengqian Huang, Rong Zhang, Feng Chen, Wenbin Li","doi":"10.1002/acn3.70166","DOIUrl":"https://doi.org/10.1002/acn3.70166","url":null,"abstract":"<p><strong>Objective: </strong>Recurrent high-grade gliomas have a poor prognosis and limited therapeutic options. This study aimed to evaluate the safety and efficacy of SYHA1813, a dual inhibitor of VEGFR and CSF1R, in patients with recurrent high-grade gliomas.</p><p><strong>Methods: </strong>Eligible patients (aged ≥ 18) with histologically or cytologically confirmed recurrent high-grade gliomas were included. Patients were administered different doses of SYHA1813 daily to assess its safety and initial efficacy.</p><p><strong>Results: </strong>Sixty-four individuals with high-grade gliomas were enrolled. Treatment-related adverse events (TRAEs) were reported in 92.2% of the patients, with 40.6% experiencing grade 3 or higher TRAEs. No grade 5 TRAE was reported. The overall objective response rate (ORR) and disease control rate (DCR) were 18.8% (95% confidence interval [CI], 10.1-30.5) and 51.6% (95% CI, 38.7-64.3), respectively. With a median follow-up duration of 9.5 months, the median progression-free survival (PFS) was 2.8 months (95% CI, 2.3-4.2) with PFS-6 of 22.5% (95% CI, 11.8-35.4) and the median OS was 15.1 months (95% CI, 10.2-NE) with OS-12 of 63.3% (95% CI, 49.3-74.4). Among the 38 patients with glioblastoma, the ORR was 18.4% (95% CI, 7.7-34.3), with a DCR of 52.6% (95% CI, 35.8-69.0). The median PFS and OS were 4.1 months (95% CI, 2.3-5.3) and 13.0 months (95% CI, 9.1-NE), respectively. SYHA1813 was detected in cerebrospinal fluid samples and the drug concentration to plasma free drug concentration ratio was 0.30-1.27.</p><p><strong>Interpretation: </strong>SYHA1813 exhibits encouraging anti-tumor activity with a manageable safety profile for the treatment of recurrent high-grade gliomas, especially glioblastoma.</p><p><strong>Trial registration: </strong>chictr.org.cn (ChiCTR2100045380).</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Evaluation of Givinostat in Duchenne Muscular Dystrophy, and Natural History Comparisons.","authors":"Craig M McDonald, Michela Guglieri, Dragana Vučinić, Gyula Acsadi, John F Brandsema, Claudio Bruno, Erika L Finanger, Amy Harper, Mercedes Lopez Lobato, Riccardo Masson, Nuria Muelas, Francina Munell, Yoram Nevo, Yann Péréon, Han Phan, Valeria A Sansone, Mariacristina Scoto, Tracey Willis, Richard S Finkel, Krista Vandenborne, Sara Cazzaniga, Silvia Montrasio, Federica Alessi, Paolo Bettica, Eugenio Mercuri","doi":"10.1002/acn3.70165","DOIUrl":"10.1002/acn3.70165","url":null,"abstract":"<p><strong>Objectives: </strong>This ongoing, open-label extension study is evaluating the long-term safety, tolerability, and efficacy of givinostat, a Class I and II histone deacetylase inhibitor, in patients with Duchenne muscular dystrophy (DMD).</p><p><strong>Methods: </strong>The recruited patients completed one of two prior clinical studies (one Phase 2 and one Phase 3 [EPIDYS]), receiving givinostat or placebo, or were successfully screened but not randomized into EPIDYS. All receive givinostat oral suspension open-label at a flexible, weight-based dose in addition to systemic corticosteroids, and attend visits every 4 months.</p><p><strong>Results: </strong>A total of 194 patients are included in the current analyses, with a mean duration of givinostat exposure (excluding use in prior studies) of 559.6 days (SD 373.0); when including use in the prior studies, the maximum exposure to givinostat was > 8 years. Although the majority of patients reported ≥ 1 adverse event (169/194 [87.1%]), most were mild/moderate in severity, and the safety profile of givinostat was consistent with prior studies. Post hoc comparisons with natural history datasets (ImagingDMD and CINRG) suggest, in propensity matched populations, givinostat added to systemic corticosteroids significantly delayed the loss of the ability to rise from the floor, the loss of the ability to complete the 4-stair climb test, and the loss of ambulation (by medians of 2.0-3.3 years; all nominal p < 0.05).</p><p><strong>Interpretation: </strong>Overall, the safety and tolerability of long-term administration of givinostat in patients with DMD was consistent with previous studies. Comparisons with natural history data suggest that givinostat delays the occurrence of major disease progression milestones.</p><p><strong>Trial registration: </strong>EudraCT number: 2017-000397-10; ClinicalTrials.gov identifier: NCT03373968.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical Thrombectomy for TRACE-III-Eligible Patients With Ischemic Stroke: A Multicenter Retrospective Study Compared to TRACE-III and TIMELESS Trials","authors":"Chongyang Huang,&nbsp;Yanru Liu,&nbsp;Jiangang Zhang,&nbsp;Sheng Guan,&nbsp;Tao Quan,&nbsp;Zhen Chen,&nbsp;Xiaojie Fu,&nbsp;Sen Wei,&nbsp;Kaihao Han,&nbsp;Xiaoan Zhou,&nbsp;Chengcheng Zhu,&nbsp;Edgar Samaniego,&nbsp;Yueqi Zhu,&nbsp;Haowen Xu","doi":"10.1002/acn3.70107","DOIUrl":"10.1002/acn3.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The results of the TRACE-III trial demonstrated that tenecteplase (TNK) might be comparable to TNK combined with mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke within 4.5 to 24 h of onset, as tested in the TIMELESS trial. We aimed to evaluate the safety and effectiveness of MT alone in TRACE-III-eligible patients in routine clinical settings, comparing the results of both trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective multicenter cohort study involved consecutive patients who underwent MT alone at three stroke centers between March 2021 and July 2024. Only those meeting the inclusion and exclusion criteria of TRACE-III were included. Safety, clinical, and imaging outcomes were compared with the TRACE-III and TIMELESS trial data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>336 TRACE-III-eligible patients were enrolled in our cohort. MT alone had a higher percentage of patients with a modified Rankin scale (mRS) score of 0–2 at 90 days (58.9%) compared to the TNK group in TRACE-III, TNK and placebo groups in TIMELESS (43.6%, 46.0%, and 42.4%, respectively; all <i>p</i> &lt; 0.01). Additionally, MT achieved a higher rate of early-stage reperfusion (86.0%) compared to the TRACE-III TNK, TIMELESS TNK, and TIMELESS placebo groups (27.9%, 76.7%, and 63.9%; all <i>p</i> &lt; 0.05). The mRS 0–1 at 90 days, incidence of symptomatic intracerebral hemorrhage, and mortality at 90 days were 36.0%, 5.4%, and 14.9%, respectively, similar to those in the three groups (all <i>p</i> &gt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In clinical practice, MT can achieve higher rate of early-stage reperfusion and tended to yield better functional outcomes than intravenous TNK, with similar safety, in TRACE-III-eligible patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1886-1893"},"PeriodicalIF":3.9,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858721","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":"Quantitative Iron Measurements in the Basal Ganglia of NBIA Patients Using QSM: Insights From a Tertiary Center.","authors":"Özge Uygun, Alpay Özcan, Fuat Kaan Aras, Evrim Bozdemir, Sibel Uğur İşeri, Murat Gültekin, Nihan Hande Akçakaya, Orkhan Mammadov, Gülay Kır, Dilek İnce Günal, Neşe Tuncer, Fatma Betül Özdilek, Banu Özen Barut, Ercan Köse, Hülya Apaydın, Asuman Ali, Sultan Çağırıcı, Pınar Topaloğlu, Alp Dinçer, Zuhal Yapıcı","doi":"10.1002/acn3.70161","DOIUrl":"https://doi.org/10.1002/acn3.70161","url":null,"abstract":"<p><strong>Objective: </strong>Neurodegeneration with brain iron accumulation (NBIA) comprises rare genetic disorders characterized by predominantly extrapyramidal symptoms and iron deposition in the basal ganglia. Conventional magnetic resonance imaging (MRI) detects qualitative changes but cannot accurately quantify iron accumulation. Quantitative susceptibility mapping (QSM) allows precise in vivo quantification of iron, providing insight into the pathophysiology of the disease.</p><p><strong>Methods: </strong>We studied 27 genetically confirmed NBIA patients and 11 age-matched healthy controls using susceptibility-weighted imaging (SWI) on a 3 Tesla MRI scanner. Basal ganglia regions of interest (ROIs) were manually delineated and QSM values were extracted.</p><p><strong>Results: </strong>Sixteen NBIA patients and 11 controls were analyzed. QSM showed significantly higher iron in the globus pallidus (GP) (p = 0.008), with PKAN patients showing a 2.5-fold increase in GP iron (p = 0.001). MPAN patients showed 2.5 times higher iron in both GP and substantia nigra (SN). A GP iron level > 0.1133 ppm increased the likelihood of PKAN 18-fold. Atypical PKAN cases had 2.5 times higher SN iron levels compared to classic cases.</p><p><strong>Interpretation: </strong>QSM is a sensitive and noninvasive tool for detecting and quantifying iron accumulation in NBIA. The GP consistently showed the highest susceptibility values across subtypes, emphasizing its significant role in disease pathology. Distinct patterns of iron deposition in different NBIA subtypes may reflect subtype-specific mechanisms with diagnostic and therapeutic relevance. Age-related susceptibility changes were found to be significant, reinforcing the need to account for age when interpreting QSM data. More importantly, QSM may serve as a candidate biomarker for longitudinal disease monitoring in future clinical trials targeting disease-modifying therapies in NBIA.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilateral versus Unilateral Training With Rhythmic Auditory Cueing in Stroke Rehabilitation: Effects on Upper Limb Function and Interhemispheric Inhibition.","authors":"Fangfang Qian, Yanhong Dai, Guoqiang Zheng, Qi Zhong, Jianliang Lu, Luying Hu, Youhua He, Zhuoming Chen","doi":"10.1002/acn3.70162","DOIUrl":"https://doi.org/10.1002/acn3.70162","url":null,"abstract":"<p><strong>Background: </strong>Stroke is a leading cause of long-term disability in adults, with upper limb hemiparesis being a common impairment. Traditional training is mostly aimed at paralyzed limbs, but the effect of bilateral training is still unclear.</p><p><strong>Objective: </strong>This study explores the influence and mechanism of unilateral and bilateral rhythmic task training on the rehabilitation of stroke patients.</p><p><strong>Study design: </strong>This was a double-blind randomized controlled trial.</p><p><strong>Methods: </strong>Thirty-six patients were randomly assigned to the bilateral group or to the unilateral group. The bilateral group engaged in repetitive training involving both arms and distal hand movements, while the unilateral group focused on the affected arm. Evaluations were performed before treatment and immediately after treatment. The outcome measures included Fugl-Meyer Upper Extremity (FMA-UE), the average electromyographic values of a total of 16 muscle groups on both the unaffected and affected sides (with 8 muscle groups on each side) during maximum voluntary isometric contraction, as well as the active range of motion (ROM). Changes in interhemispheric inhibition (IHI) were assessed using transcranial magnetic stimulation.</p><p><strong>Results: </strong>Post-treatment assessments indicated that the FMA-UE scores significantly increased in both groups, with the bilateral group exhibiting more pronounced improvements (p = 0.031; ηp² = 0.130). Specifically, compared to their pre-treatment states, the bilateral group showed statistically significant differences in the maximum EMG amplitudes of the anterior deltoid (p = 0.006; ηp² = 0.204) and wrist flexor muscles (p < 0.001; ηp² = 0.308) on the affected side, with greater gains than the unilateral group. Additionally, the maximum EMG amplitudes of the biceps brachii (p = 0.035; ηp² = 0.124) and wrist extensors (p = 0.018; ηp² = 0.153) on the unaffected side were significantly enhanced in the bilateral group. In terms of active ROM, the bilateral group demonstrated significant improvements in shoulder flexion (p = 0.024; ηp² = 0.142) and wrist flexion (p = 0.020; ηp² = 0.149), which surpassed those observed in the unilateral group. Furthermore, a significant reduction in IHI (p = 0.023; ηp² = 0.196) was observed, which was positively correlated with FMA-UE scores following bilateral training (r = 0.85, p < 0.001).</p><p><strong>Conclusion: </strong>Bilateral training is more effective than unilateral training in enhancing upper limb function and may contribute to balancing IHI in stroke recovery patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs on Acute Intracerebral Hemorrhage.","authors":"Shin-Joe Yeh, Sung-Chun Tang, Li-Kai Tsai, Jiann-Shing Jeng","doi":"10.1002/acn3.70163","DOIUrl":"https://doi.org/10.1002/acn3.70163","url":null,"abstract":"<p><strong>Objective: </strong>Despite celecoxib, a cyclooxygenase-2 inhibitor, promoting functional recovery from intracerebral hemorrhage (ICH) by reducing inflammation-mediated perihematomal edema in rat models, the evidence of its effects on patient outcomes remains limited. As nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate inflammation by inhibiting cyclooxygenase-2, this study aimed to assess the impact of non-aspirin NSAIDs on ICH outcomes.</p><p><strong>Methods: </strong>Patients with acute ICH admitted to our hospital between January 2015 and December 2020 were prospectively enrolled and retrospectively categorized based on pre- or post-ICH use of non-aspirin NSAIDs. Outcomes were assessed using the modified Rankin Scale (mRS) score at 3 months, survival at 1 year, and mortality at long-term follow-up.</p><p><strong>Results: </strong>Among 976 patients with acute ICH, 2.0% and 15.0% were non-aspirin NSAID users before and after ICH, respectively. Post-ICH non-aspirin NSAID use was associated with a reduced 1-year mortality risk (adjusted odds ratio [aOR] 0.30, p = 0.001) and long-term mortality risk (adjusted hazard ratio 0.56, p = 0.043), but not good functional outcomes (mRS 0-2) (aOR 0.98, p = 0.940). In the subgroup analyses, post-ICH use might be linked to good functional outcomes in patients with lobar hemorrhage or in those without surgical intervention. Pre-ICH non-aspirin NSAID use was not associated with these outcomes in the overall population, but it might be linked to increased mortality in subgroups with lobar hemorrhage, cerebral amyloid angiopathy, hyperlipidemia, or without intraventricular hemorrhage.</p><p><strong>Interpretation: </strong>The post-ICH use of non-aspirin NSAIDs reduced mortality. Future studies are warranted to identify specific non-aspirin NSAID regimens that can significantly improve the outcomes of patients with ICH.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine, Chemokine, and Neurofilament Light Chain Signatures in LGI1 Autoimmune Encephalitis.","authors":"Albert Aboseif, Georgios Mangioris, Binxia Yang, Vanessa K Pazdernik, Jeffrey W Britton, Divyanshu Dubey, Eoin P Flanagan, Sarosh R Irani, Gregory S Day, Charles L Howe, A Sebastian López-Chiriboga, Andrew McKeon, John R Mills, Yahel Segal, Michel Toledano, Ivana Vodopivec, Sean J Pittock, Anastasia Zekeridou","doi":"10.1002/acn3.70158","DOIUrl":"https://doi.org/10.1002/acn3.70158","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the value of cytokine, chemokine, and neurofilament light chain (NfL) concentrations in predicting relapse risk, chronic epilepsy, and functional impairment in LGI1 autoimmune encephalitis (AE).</p><p><strong>Methods: </strong>Cytokines/chemokines (IL-1-beta, IL-2, IL-4, IL-5, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-13, IL-17A, GM-CSF, TNF-alpha, IFN-gamma, CXCL9, CXCL10, CXCL13, BAFF) and NfL concentrations were measured in CSF and paired serum from LGI1-AE patients evaluated at Mayo Clinic (01/2015-02/2024), using a multiplex immunoassay system (ELLA, Bio-Techne) and correlated with clinical outcomes. A laboratory-based cohort of LGI1-IgG-positive patients and control cohorts, including patients with mixed non-inflammatory disorders (MNID), Alzheimer's disease (AD), and temporal lobe epilepsy (TLE) were analyzed.</p><p><strong>Results: </strong>Forty-four patients with LGI1-AE were included; 29 (66%) were male, with a median age of 68.5 years (range, 8-85). Median time from symptom onset to CSF sampling was eight months (IQR, 3-17); 19/42 (45%) experienced a clinical relapse and 27% developed chronic epilepsy. Serum IL-6, serum and CSF IL-8/CXCL8, and IL-17A were higher in LGI1-IgG positive patients than MNID (p < 0.05). TLE cytokine/chemokine profiles were similar to LGI1 AE; AD patients had lower serum IL-6 and CSF IL-8/CXCL8 (p = 0.04; p = 0.01), and higher serum IL-17A and GM-CSF (p = 0.004; p = 0.01) than LGI1-AE. Higher CSF IL-6 and IL-8/CXCL8 in LGI1-AE associated with clinical relapse (p < 0.05) and higher CSF NfL associated with chronic epilepsy (p = 0.01).</p><p><strong>Conclusion: </strong>Elevations in IL-6, IL-8/CXCL8, and IL-17A were identified in this LGI1-AE cohort. CSF IL-6, IL-8/CXCL8, and NfL levels are potential prognostic biomarkers for risk of relapse and chronic epilepsy in LGI1-AE.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Letter: \"Real-World Clinical Experience With Serum MOG and AQP4 Antibody Testing by Live Versus Fixed Cell-Based Assay\".","authors":"Yana Said, Eoin P Flanagan, Elias S Sotirchos","doi":"10.1002/acn3.70169","DOIUrl":"https://doi.org/10.1002/acn3.70169","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durable B-Cell Impairment While Sparing IgA B Cells After Ocrelizumab Therapy in Multiple Sclerosis.","authors":"Alexandra Garcia, Stephane Rodriguez, Emilie Dugast, Christine Lebrun-Frenay, Eric Thouvenot, Jérôme de Sèze, Emmanuelle Le Page, Sandra Vukusic, Inès Doghri, Eric Berger, Olivier Casez, Pierre Labauge, Aurélie Ruet, Catarina Raposo, Fabienne Le Frère, Arnaud B Nicot, Sandrine Wiertlewski, Pierre-Antoine Gourraud, Laure Michel, Laureline Berthelot, David-Axel Laplaud","doi":"10.1002/acn3.70135","DOIUrl":"https://doi.org/10.1002/acn3.70135","url":null,"abstract":"<p><strong>Objectives: </strong>Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, is highly efficient in relapsing-remitting multiple sclerosis (RR-MS). We assessed early cellular B-cell profiles in patients prior to OCR treatment, on OCR treatment, and after 15 months of therapy discontinuation. This study aims to provide new clues about the mechanisms of action of OCR and about disease pathophysiology.</p><p><strong>Methods: </strong>Patients with early, treatment-naive, RR-MS were included from 11 centers participating in an ancillary study of the ENSEMBLE trial (NCT03085810) to evaluate the effectiveness and safety of OCR. The phenotypic B-cell immune profile was comprehensively assessed in 18 patients by spectral flow cytometry at baseline, after 1 year of OCR treatment, and compared with 10 healthy volunteers (HVs) (matched for age and sex) on cryopreserved peripheral blood mononuclear cells (PBMC). We also analyzed B-cell reconstitution after a median time of 15 months after trial withdrawal in three patients by flow cytometry and single-cell RNA sequencing.</p><p><strong>Results: </strong>Using spectral flow cytometry we defined the proportions and absolute numbers of naive, transitional, Ig-G, Ig-A, Ig-M memory B cells, Ig-G, Ig-A, Ig-M plasmablasts, and plasma cells. At baseline we found an increased frequency of IgG-secreting B cells in MS patients compared to HV. During OCR treatment, the proportion of the different subsets of B cells was strongly modified. In the mature clusters, we observed that the treatment partially spared memory IgA B cells. In parallel, we observed that differentiated IgA plasmablasts and plasma cells were more increased than the other differentiated clusters. Interestingly, in the three patients who stopped the treatment single-cell RNA sequencing showed that the B cells that reappeared were mainly naive with an inflammatory and migratory phenotype concomitantly to a rise of regulatory B cells.</p><p><strong>Discussion: </strong>Our findings support an increased regulatory phenotype of remaining B cells under treatment with OCR and replenishment of undifferentiated B cells accumulating features of inflammatory and migratory patterns after OCR discontinuation, counterbalanced by an increased proportion of regulatory B cells.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ICU-EEG Pattern Detection by a Convolutional Neural Network.","authors":"Giulio Degano, Hervé Quintard, Andreas Kleinschmidt, Nikita Francini, Oana E Sarbu, Pia De Stefano","doi":"10.1002/acn3.70164","DOIUrl":"https://doi.org/10.1002/acn3.70164","url":null,"abstract":"<p><strong>Objective: </strong>Patients in the intensive care unit (ICU) often require continuous EEG (cEEG) monitoring due to the high risk of seizures and rhythmic and periodic patterns (RPPs). However, interpreting cEEG in real time is resource-intensive and heavily relies on specialized expertise, which is not always available. This study introduces a lightweight convolutional neural network (CNN) to automatically detect key EEG patterns, including seizures and RPPs.</p><p><strong>Methods: </strong>We classified time-frequency spectrograms of EEG data from the Harmful Brain Activity Classification challenge, including 1950 patients. We tested our model on a subset of this dataset and a small independent cohort of ICU patients with epileptic seizures from the Geneva University Hospital.</p><p><strong>Results: </strong>Our model showed good performance metrics on the open-source data with an AUROC score of 93% for SZ, 91% for lateralized PD, 94% for generalized PD, 87% for lateralized RDA, 89% for generalized RDA, and 88% for others. The evaluation with the Geneva University Hospital dataset also demonstrated strong temporal detection capabilities, showing an false positive rate (FPR) of 22%, 20%, and 21% at 50 s, 30 s, and 20 s before seizure onset, and a true positive rate (TPR) of 76%, 84%, and 89% at 20 s, 30 s, and 50 s after seizure onset.</p><p><strong>Interpretation: </strong>This study presents a lightweight CNN model capable of detecting critical EEG patterns in ICU patients with minimal preprocessing. Moreover, the model's design provides reliable detection of ICU-EEG epileptic patterns shortly after their onset. These features underscore the model's potential to enhance timely EEG monitoring in resource-limited and advanced clinical contexts.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}