Annals of Clinical and Translational Neurology最新文献

{"title":"Ofatumumab in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Comparison With Rituximab.","authors":"Yuxin Fan, Lei Zhou, Jingzi ZhangBao, Hongmei Tan, Zhouzhou Wang, Chao Quan","doi":"10.1002/acn3.70392","DOIUrl":"https://doi.org/10.1002/acn3.70392","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy and safety of ofatumumab in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and compare it with rituximab.</p><p><strong>Methods: </strong>We conducted a single-center, observational study including 22 MOGAD patients treated with ofatumumab and 21 treated with rituximab. The primary outcome is relapse, while the secondary outcomes are disability status and adverse events.</p><p><strong>Results: </strong>Twenty-two patients received ofatumumab for a median duration of 19.5 months (range 6-41). Among them, 18 patients (81.82%) remained relapse-free during follow-up. Annualized relapse rate (ARR) significantly decreased from 1.30 (95% CI 0.74-2.29) pretreatment to 0.12 (95% CI 0.04-0.35) during ofatumumab therapy (IRR 10.86, 95% CI 3.22-36.70, p < 0.001). Through propensity score matching, 11 patients in the ofatumumab group and 11 patients in the rituximab group were compared. Ofatumumab was observed to be associated with a significantly lower risk of a second attack (HR 0.233, 95% CI 0.061 to 0.893, p = 0.018) compared to rituximab. Adverse events were reported in 54.55% patients (6/11) treated with ofatumumab, most of which were mild and occurred after the initial dose.</p><p><strong>Interpretation: </strong>Ofatumumab was associated with a lower relapse risk compared with rituximab in patients with MOGAD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757744","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":"Movement Disorders in Aicardi-Goutières Syndrome and Response to Immunomodulation.","authors":"Enrique Gonzalez Saez-Diez, Monica Ferrer Socorro, Kathryn Yang, Nicole Battaglia, Zainab Zaman, Mariko Bennett, Adeline Vanderver, Pui Y Lee, Lauren A Henderson, Milena M Andzelm, Darius Ebrahimi-Fakhari","doi":"10.1002/acn3.70407","DOIUrl":"https://doi.org/10.1002/acn3.70407","url":null,"abstract":"<p><p>This study characterizes movement disorders and treatment responses in seven children with Aicardi-Goutières syndrome (AGS). We retrospectively evaluated motor phenotypes, neuroimaging, and interferon signatures in patients treated with baricitinib or anifrolumab. Spasticity affected all patients, while dystonia was present in 4/7. GMFCS levels ranged from I to V. Following immunomodulation, interferon signatures normalized in 6/7 of patients, and 6/7 showed clinical stabilization or improvement, with no further regression events. These findings indicate that targeted therapy was associated with reduced systemic inflammation and stabilized disease. However, motor outcomes varied, suggesting that established CNS injury may limit functional recovery despite a biochemical response.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757709","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":"Neurovascular Contacts in the Pathophysiology of Neuralgic Amyotrophy: An Observational Study.","authors":"Johannes Fabian Holle, Andreas Leha, Volker Limmroth, Wolfram Windisch, Maximilian Zimmermann","doi":"10.1002/acn3.70416","DOIUrl":"https://doi.org/10.1002/acn3.70416","url":null,"abstract":"<p><strong>Objective: </strong>Neuralgic amyotrophy (NA) is a prevalent, monophasic, multifocal immune-mediated neuropathy. A distinctive characteristic of the disease is the occurrence of nerve or fascicle constrictions and torsions (NA-associated focal nerve lesions, NAFL). The pathophysiology underlying this phenomenon remains to be fully elucidated.</p><p><strong>Methods: </strong>This study uses an observational research design with a single center, retrospective approach. We evaluated patients who presented at the outpatient clinic of a tertiary referral hospital between January 1, 2022, and August 5, 2025, due to NA. In addition to evaluating clinical and neurophysiological data, two independent experts examined the available ultrasound images for the prevalence of NAFL and the presence of arterial vascular structures in the immediate vicinity.</p><p><strong>Results: </strong>A total of 171 affected nerves from 77 patients were analyzed. The prevalence of NAFL was 31% (24/77) among all patients. In 53% of all NAFL, direct neurovascular contact could be detected. A previous mechanical trigger was identified in 71% of patients with proven NAFL but without neurovascular contact. This was the case in only 29% of patients with neurovascular contact, although this discrepancy did not attain statistical significance.</p><p><strong>Interpretation: </strong>The frequency of neurovascular contacts in close proximity to NAFL suggests that these contacts play a role in its pathophysiology. Such contacts, similar to mechanical tension on the nerve, could lead to a local disruption of the blood-nerve barrier. This would explain phenomena inconsistent with the current pathophysiological model, such as the lack of preference for the dominant arm and NAFL's occurrence at certain anatomical sites.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757746","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":"Persistent Bilateral [¹⁸F]THK5351 and Migrating Unilateral [¹⁸F]FDG Uptake in Anti-LGI1 Encephalitis.","authors":"Yusuke Akitomi, Kenichiro Taira, Masanori Kurihara, Kenji Ishibashi, Kenji Ishii, Fumio Suzuki, Aya Midori Tokumaru, Makoto Hara, Atsushi Iwata","doi":"10.1002/acn3.70410","DOIUrl":"https://doi.org/10.1002/acn3.70410","url":null,"abstract":"<p><p>Anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1-E) can cause persistent cognitive deficits, but the mechanisms remain unclear. A 40-year-old woman with LGI1-E presented with subacute cognitive deficits and showed mild left medial temporal lobe (MTL) swelling and fluid-attenuated inversion recovery (FLAIR) hyperintensity on initial magnetic resonance imaging (MRI). Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) demonstrated left MTL hypermetabolism, whereas [¹⁸F]THK5351 PET/CT revealed bilateral MTL uptake. Although immunotherapy improved her symptoms, mild cognitive deficits persisted. FLAIR hyperintensity resolved, but [¹⁸F]FDG PET/CT demonstrated transient right MTL hypermetabolism during relapse, whereas [¹⁸F]THK5351 PET/CT showed partial decline over time, although relatively increased right-sided uptake persisted throughout follow-up. These findings highlight a dissociation between episodic metabolic changes on [¹⁸F]FDG PET/CT and more persistent medial temporal MAO-B-related uptake on [¹⁸F]THK5351 PET/CT, which may be associated with residual cognitive deficits.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758010","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":"RNA Sequencing Resolves Cryptic Pathogenic Variants in Mitochondrial Disease.","authors":"Zhimei Liu, Xin Duan, Fatemeh Peymani, Jia Wang, Chengjia Bao, Chaolong Xu, Ying Zou, Zixuan Zhang, Yunxi Zhang, Tongyue Li, Martin Pavlov, Junling Wang, Minhan Song, Tianyu Song, Xiaodi Han, Mingxi Sun, Danmin Shen, Ruoyu Duan, Huafang Jiang, Manting Xu, Holger Prokisch, Fang Fang","doi":"10.1002/acn3.70379","DOIUrl":"https://doi.org/10.1002/acn3.70379","url":null,"abstract":"<p><strong>Objective: </strong>Mitochondrial diseases are the most common inherited metabolic disorders, characterized by pronounced clinical and genetic heterogeneity that complicates molecular diagnosis. Although DNA-based sequencing approaches have become standard in genetic testing, up to half of patients remain without a definitive diagnosis. We aimed to perform RNA sequencing (RNA-seq) of patient-derived skin fibroblasts to enhance the molecular diagnostic efficacy of mitochondrial disease in undiagnosed cases in China.</p><p><strong>Methods: </strong>We performed RNA-seq on skin fibroblasts from 140 pediatric patients with suspected mitochondrial disease who remained genetically undiagnosed after whole exome sequencing (WES). Aberrant RNA expression and splicing were identified using the detection of RNA outliers pipeline (DROP). Based on WES findings, patients were stratified into a candidate group (n = 28), in which RNA-seq evaluated the pathogenicity of WES-identified variants of uncertain significance and an unsolved group (n = 112), in which RNA-seq was used to pinpoint candidate genes. In six cases where RNA-seq identified the aberrant RNA event but WES did not detect the causative variants, whole genome sequencing (WGS) was performed.</p><p><strong>Results: </strong>Integrative RNA-seq, WES, and WGS analysis resulted in a genetic diagnosis in 25% of patients overall (20/28 [71%] in the candidate group; 15/112 [13%] in the unsolved group). Aberrant splicing explained most candidate-group diagnoses, including variants misclassified by in silico predictors such as SpliceAI. 14% of protein-truncating variants predicted to undergo nonsense-mediated decay (NMD) escaped degradation, highlighting the functional limits of current predictions. The variants identified in the unsolved cohort included synonymous, missense, deep intronic, near-splice-site variants, and large deletions. The most frequent among them was a recurrent synonymous East Asian founder mutation in ECHS1, accounting for seven cases. Interestingly, across 233 pathogenic variants associated with aberrant RNA phenotypes compiled from this study and prior reports, half were noncoding and half were coding variants.</p><p><strong>Conclusion: </strong>RNA-seq substantially enhances molecular diagnosis in mitochondrial disease by exposing cryptic splicing, regulatory, and NMD-escape events invisible to DNA sequencing alone. These data advocate transcriptome analysis as an essential component of comprehensive genomic diagnostics in neurometabolic disease.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758045","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":"Comparative Effectiveness and Safety of Inebilizumab Versus Rituximab in AQP4-IgG-Positive NMOSD.","authors":"Jie Lin, Binbin Xue, Dewei Xie, Jia Li, Juyuan Pan, Lanbing Zhu, Qiaowen Tong, Jing Lin, Ruofan Zhu, Xu Zhang, Junhui Xia, Xiang Li","doi":"10.1002/acn3.70412","DOIUrl":"https://doi.org/10.1002/acn3.70412","url":null,"abstract":"<p><strong>Objective: </strong>Rituximab (anti-CD20, RTX) and inebilizumab (anti-CD19, INE) represent B-cell-depleting therapies used for aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD); however, direct comparative evidence remains limited. This study aimed to evaluate the real-world comparative effectiveness and safety of RTX versus INE.</p><p><strong>Design: </strong>This was a retrospective, multicenter, observational study.</p><p><strong>Methods: </strong>In this retrospective cohort study, 103 patients with AQP4-IgG+ NMOSD were included, of whom 40 received INE and 63 received RTX. Overlap weighting based on propensity scores was employed to balance baseline covariates, achieving excellent balance (all standardized mean differences < 0.001). The primary outcomes included annualized relapse rate (ARR) and relapse risk, which were analyzed using weighted Poisson regression and Anderson-Gill mode.</p><p><strong>Results: </strong>After weighting, the proportion of patients experiencing any relapse was lower in the INE group than in the RTX group (10.6% vs. 43.9%, p = 0.047). In models accounting for differences in follow-up duration, INE was also associated with a lower post-treatment relapse risk than RTX. Although the restricted mean survival time difference at 27 months favored INE, the difference was not statistically significant. Disability progression was similar between groups, though hypogammaglobulinemia, particularly reduced IgG levels, was more frequently observed with INE (54.1% vs. 17.2%; p < 0.001).</p><p><strong>Conclusions: </strong>In this real-world cohort, INE showed a trend toward lower relapse risk compared to RTX, whereas demonstrating a manageable safety profile with increased incidence of hypogammaglobulinemia.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758082","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":"Anti-CD19 CAR T Cells in Autoimmune Encephalitis: Inflammation Controlled, Neurodegeneration Unchecked?","authors":"Dimitrios Mougiakakos, Marwa Al-Dubai, Denise Walther, Dominic Borie, Jan D Lünemann, Marc Pawlitzki, Sven G Meuth, Solveig Henneicke, Stefan Vielhaber, Stefanie Schreiber","doi":"10.1002/acn3.70414","DOIUrl":"https://doi.org/10.1002/acn3.70414","url":null,"abstract":"<p><p>Just recently, successful chimeric antigen receptor (CAR) T cell therapy was reported in the first patient with refractory, anti-diacylglycerol lipase alpha (DAGLA) antibody-mediated autoimmune encephalitis, achieving partial clinical remission. We now provide extended follow-up demonstrating a stable, relapse-free clinical course and persistent suppression of autoantibodies. However, the patient exhibited progressive neurodegeneration despite sustained control of B cell-mediated inflammation. This dissociation between immune quiescence and structural decline highlights that CAR T cell therapy, while highly effective in extinguishing inflammation, may not be sufficient to prevent or reverse ongoing neuronal damage in disorders characterized by both inflammation and neurodegeneration.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758057","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":"The Tale of the Residual Tail: Insights From Continuous Intracranial Monitoring From Post-Hippocampectomy Dynamics.","authors":"Patrick Hartnett, Syeda Amrah Hashmi, Amaan Qureshi, Heather Spader, Shayan Moosa, Ifrah Zawar","doi":"10.1002/acn3.70413","DOIUrl":"https://doi.org/10.1002/acn3.70413","url":null,"abstract":"<p><p>Subtotal hippocampal resection can leave residual hippocampal tissue, yet the immediate postoperative electrophysiologic evolution of such remnants is unknown. We describe a patient with drug-resistant temporal lobe epilepsy in whom a hippocampal remnant was continuously monitored using a responsive neurostimulator (RNS) following subtotal hippocampal resection. Postoperative electrocorticography demonstrated persistent electrographic status epilepticus for 3 days, followed by a transient 5-day quiescent period and delayed recurrence of electrographic and clinical seizures on postoperative day eight. This case provides rare, real-time insight into the dynamic temporal evolution of residual hippocampal excitability after surgery and offers a potential mechanistic explanation for delayed postoperative seizure recurrence following incomplete hippocampal resection.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758043","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":"Elevated Connectivity During Language Processing Is Associated With Cognitive Performance in SeLECTS.","authors":"Wendy Qi, Katharine Lee, Kerry C Nix, Miguel Menchaca, Xiwei Shé, Lorelei Santa Maria, Wei Wu, Zihuai He, Fiona M Baumer","doi":"10.1002/acn3.70369","DOIUrl":"https://doi.org/10.1002/acn3.70369","url":null,"abstract":"<p><strong>Objective: </strong>Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) is associated with language impairments despite seizures originating in the motor cortex, suggesting aberrant cross-network interactions. Here we tested whether functional connectivity in SeLECTS during language tasks predicts language performance.</p><p><strong>Methods: </strong>We recorded high-density EEG from right-handed children with SeLECTS (n = 31) and age-matched controls (n = 32) during verb generation, repetition, and resting tasks. Phonological awareness was assessed using the Comprehensive Test of Phonological Processing-2. Connectivity between bilateral motor cortices and language regions (the left inferior frontal and superior temporal cortices and their right hemisphere homologs) was measured using the weighted Phase Lag Index (wPLI).</p><p><strong>Results: </strong>Children with SeLECTS demonstrated significantly elevated connectivity between motor and language regions during language processing. Motor-to-frontal connectivity was higher in SeLECTS during both verb generation and repetition tasks. Frontal-to-temporal connectivity was elevated specifically during verb generation. Exploratory analyses suggest high interhemispheric connectivity (between the left and right hemispheres) during language tasks is associated with poor phonological awareness in children with SeLECTS, but not controls. Together, we found that children with SeLECTS exhibited pathologically elevated connectivity between motor and language networks that was strongly associated with impaired phonological awareness.</p><p><strong>Interpretation: </strong>These findings establish task-specific connectivity abnormalities as a characteristic feature of SeLECTS and suggest interhemispheric connectivity patterns may relate to language outcomes, warranting further investigation as potential targets for therapeutic neuromodulation.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727670","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":"Limitations of Complement Activity Assays as Biomarkers for Ravulizumab Therapeutic Monitoring.","authors":"Francesco Saccà, Ryan Pelto","doi":"10.1002/acn3.70402","DOIUrl":"https://doi.org/10.1002/acn3.70402","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727753","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}