Annals of Clinical and Translational Neurology最新文献

{"title":"Erratum to \"Inferring Disease Course From Differential Exon Usage in the Wide Titinopathy Spectrum\".","authors":"","doi":"10.1002/acn3.52274","DOIUrl":"https://doi.org/10.1002/acn3.52274","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179549","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":"SARS-CoV-2 Is Linked to Brain Volume Loss in Multiple Sclerosis.","authors":"Tomas Uher, Dominika Stastna, Ingrid Menkyova, Vaclav Capek, Jiri Lindner, Petra Nytrova, Jan Krasensky, Eliza Varju, Miguel D'haeseleer, Eva Kubala Havrdova, Dana Horakova, Manuela Vaneckova, Niels Bergsland","doi":"10.1002/acn3.70091","DOIUrl":"https://doi.org/10.1002/acn3.70091","url":null,"abstract":"<p><strong>Objective: </strong>The impact of SARS-CoV-2 infection on brain and spinal cord pathology in patients with multiple sclerosis (pwMS) remains unclear. We aimed to describe changes in brain lesion activity and brain and spinal cord volumes following SARS-CoV-2 infection.</p><p><strong>Methods: </strong>We included 177 pwMS (570 MRI scans) diagnosed with and tested positive for SARS-CoV-2 infection between August 2020 and May 2021. All patients were free of clinical disease activity, disease-modifying therapy changes, and corticosteroids during the study. MRI scans were performed using a standardized protocol on a 3-Tesla scanner. We analyzed the effect of SARS-CoV-2 on brain lesion load accrual and brain and spinal cord volume measures using adjusted mixed-effect models.</p><p><strong>Results: </strong>During SARS-CoV-2 infection, patients had a median disease duration of 14.2 years, a median age of 44.9 years, and a median Expanded Disability Status Scale of 2.0. SARS-CoV-2 infection did not lead to any changes in the number or volume of T1 or T2 lesions in the brain. However, SARS-CoV-2 was associated with an increased whole brain (B = -0.17; SE = 0.08; p = 0.028), grey matter (B = -0.25; SE = 0.12; p = 0.040), and cortical grey matter volume loss (B = -0.32; SE = 0.13; p = 0.014). Greater ventricular enlargement following SARS-CoV-2 infection was evident only in individuals over the age of 40 (interaction of age vs. ventricular enlargement: B = 0.17; SE = 0.05; p = 0.0003). Only patients with more severe SARS-CoV-2 infection showed a reduction in mean upper cervical cord area (MUCCA) (B = 1.14; SE = 0.52; p = 0.030).</p><p><strong>Interpretation: </strong>SARS-CoV-2 infection in clinically stable pwMS was linked to increased neuronal tissue loss.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179791","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":"Fetal Akinesia/Hypokinesia and Arthrogryposis of Neuromuscular Origin: Etiologic Groups, Genetics, and Phenotypic Spectrum.","authors":"Florencia Pérez-Vidarte, Berta Estévez-Arias, Leslie Matalonga, Delia Yubero, Anna Codina, Carlos Ortez, Julita Medina, Lidia DeSena DeCabo, Laura Carrera-García, Jesica Expósito-Escudero, Cristina Jou, Eduardo F Tizzano, Andres Nascimento, Daniel Natera-de Benito","doi":"10.1002/acn3.70088","DOIUrl":"https://doi.org/10.1002/acn3.70088","url":null,"abstract":"<p><strong>Objective: </strong>To provide a comprehensive clinical and genetic characterization of individuals with arthrogryposis multiplex congenita (AMC), focusing on the distribution of genetic etiologies across the neuromuscular spectrum and comparing myogenic and neurogenic subtypes.</p><p><strong>Methods: </strong>A total of 105 individuals with AMC were clinically and genetically evaluated in a single-center study. Participants were stratified based on the primary site of involvement, and further classification was performed for neuromuscular cases into neurogenic and myogenic subtypes. Genetic diagnoses were made through using a range of next-generation sequencing techniques, including exome sequencing (42 individuals), gene panel testing (40 individuals), genome sequencing (24 individuals), and targeted-gene testing in selected cases. In most individuals who underwent genome sequencing, this was preceded by exome or gene panel testing.</p><p><strong>Results: </strong>Of the 105 individuals, 4 were classified as Amyoplasia and 1 as FARAD. Among the remaining 100 cases, 81 (81%) presented with neuromuscular AMC, with defects involving motor neurons/peripheral nerves (52%, 42/81), neuromuscular junctions (7%, 6/81), and skeletal muscle (41%, 33/81). A genetic diagnosis was achieved in 55% (55/100) of the entire cohort and in 58% (47/81) of individuals with neuromuscular AMC. The most frequently implicated genes were TTN (16%, 9/55), CHRNG (10.9%, 6/55), PIEZO2 (9.1%, 5/55), ZC4H2 (9.1%, 5/55), DYNC1H1 (7.2%, 4/55), MYH3 (5.4%, 3/55), and RYR1 (5.4%, 3/55). Diagnostic yield varied significantly between subgroups, with 84.6% (33/39) of myogenic AMC cases genetically resolved, compared to 33.3% (14/42) of neurogenic cases. TTN was the most common gene in myogenic AMC, while ZC4H2 and DYNC1H1 were predominant in neurogenic AMC.</p><p><strong>Interpretation: </strong>This study provides a detailed phenotypic and genetic characterization of neuromuscular AMC, highlighting the most frequently affected genes and their associated phenotypes. The findings underscore the challenges in diagnosing a significant proportion of cases, especially within the neurogenic subgroup, and emphasize the importance of integrating detailed phenotypic data with genetic analysis to enhance diagnosis, prognosis, and management of family expectations.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179608","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":"Pulse Pressure, White Matter Hyperintensities, and Cognition: Mediating Effects Across the Adult Lifespan.","authors":"Jade Hannan, Sarah Newman-Norlund, Natalie Busby, Sarah C Wilson, Roger Newman-Norlund, Chris Rorden, Julius Fridriksson, Leonardo Bonilha, Nicholas Riccardi","doi":"10.1002/acn3.70086","DOIUrl":"https://doi.org/10.1002/acn3.70086","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether pulse pressure or mean arterial pressure mediates the relationship between age and white matter hyperintensity load and to examine the mediating effect of white matter hyperintensities on cognition.</p><p><strong>Methods: </strong>Demographic information, blood pressure, current medication lists, and Montreal Cognitive Assessment scores for 231 stroke- and dementia-free adults were retrospectively obtained from the Aging Brain Cohort study. Total WMH load was determined from T2-FLAIR magnetic resonance scans using the TrUE-Net deep learning tool for white matter segmentation. In separate models, we used mediation analysis to assess whether pulse pressure or MAP mediates the relationship between age and total white matter hyperintensity load, controlling for cardiovascular confounds. We also assessed whether white matter hyperintensity load mediated the relationship between age and cognitive scores.</p><p><strong>Results: </strong>Pulse pressure, but not mean arterial pressure, significantly mediated the relationship between age and white matter hyperintensity load. White matter hyperintensity load partially mediated the relationship between age and Montreal Cognitive Assessment score.</p><p><strong>Interpretation: </strong>Our results indicate that pulse pressure, but not mean arterial pressure, is mechanistically associated with age-related accumulation of white matter hyperintensities, independent of other cardiovascular risk factors. White matter hyperintensity load was a mediator of cognitive scores across the adult lifespan. Effective management of pulse pressure may be especially important for maintenance of brain health and cognition.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141093","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":"EEG Response to Sedation Interruption Complements Behavioral Assessment After Severe Brain Injury.","authors":"Charlotte Maschke, Loretta Norton, Catherine Duclos, Miriam Han, Kira Dolhan, Geoffrey Laforge, Allison Frantz, Xiaoyu Wang, Hassan Al-Hayawi, Tianyu Zhang, Raphaël Lavoie, Adrian M Owen, Stefanie Blain-Moraes","doi":"10.1002/acn3.70085","DOIUrl":"https://doi.org/10.1002/acn3.70085","url":null,"abstract":"<p><strong>Objective: </strong>Accurate assessment of the level of consciousness and potential to recover in patients with severe brain injury underpins crucial decisions in the intensive care unit but remains a major challenge for the clinical team. The neurological wake-up test is a widely used assessment tool. However, many patients' behavioral responses during a short interruption of sedation are ambiguous or absent, yielding little prognostic value. This study assesses the brain's electroencephalogram response during an interruption of propofol sedation to complement behavioral assessment during the neurological wake-up test to predict survival, recovery of consciousness, and long-term functional outcomes in patients with acute severe brain injury.</p><p><strong>Methods: </strong>We recorded 128-channel EEG from 41 severely brain-injured patients during a clinically indicated neurological wake-up test. Behavioral assessment was performed before and after interruption of propofol sedation, using the Glasgow Coma Scale. Brain response to sedation interruption was quantified using EEG power, spatial ratios, and the spectral exponent.</p><p><strong>Results: </strong>Recovery of responsiveness during the neurological wake-up test is reflected in participants' brain response to sedation interruption. Electrophysiological patterns can be decoupled from participant behavioral response, with some individuals demonstrating neurophysiological signs of waking up despite an absent behavioral response. Using the brain response to complement behavioral assessment improved prognostic value, distinguished patients according to survival and outperformed outcome predictions of the patients' attending physician.</p><p><strong>Interpretation: </strong>EEG can complement behavioral assessment during the neurological wake-up test to improve prognostication, inform clinicians, family members, and caregivers, and to set realistic goals for treatment and therapy.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141088","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":"Translating Muscle RNAseq Into the Clinic for the Diagnosis of Muscle Diseases.","authors":"Alba Segarra-Casas, Cristina Domínguez-González, Daniel Natera-de Benito, Solange Kapetanovic, Aurelio Hernández-Laín, Berta Estévez-Arias, Laura Llansó, Carlos Ortez, Cristina Jou, Itxaso Martí-Carrera, Arístides López-Márquez, Maria José Rodríguez, Laura González-Mera, Velina Nedkova, Roberto Fernández-Torrón, Benjamín Rodríguez-Santiago, Cecília Jimenez-Mallebrera, Raul Juntas-Morales, Adolfo López-de Munain, Jordi Surrallés, Andrés Nascimento, Eduard Gallardo, Montse Olivé, Pia Gallano, Lidia González-Quereda","doi":"10.1002/acn3.70078","DOIUrl":"https://doi.org/10.1002/acn3.70078","url":null,"abstract":"<p><strong>Objective: </strong>Approximately half of patients with hereditary myopathies remain without a definitive genetic diagnosis after DNA next-generation sequencing (NGS). Here, we implemented transcriptome analysis of muscle biopsies as a complementary diagnostic tool for patients with muscle disease but no definitive genetic diagnosis after exome sequencing.</p><p><strong>Methods: </strong>In total, 70 undiagnosed cases with suspected genetic muscular dystrophies or congenital myopathies were included in the study. Muscle RNAseq comprised the analysis of aberrant splicing, aberrant expression, and monoallelic expression. In addition, existing NGS data or variant calling from RNAseq were reanalyzed, and genome sequencing was performed in selected cases. Four aberrant splicing open-source tools were compared and assessed.</p><p><strong>Results: </strong>RNAseq established a diagnosis in 10/70 patients (14.3%) by identifying aberrant transcripts produced by single nucleotide variants (7/10) or copy number variants (3/10). Reanalysis of NGS data allowed the diagnosis in 9/70 individuals (12.9%). Based on this cohort, FRASER was the tool that reported more splicing outlier events per sample while showing the highest accuracy (81.26%).</p><p><strong>Conclusions: </strong>We demonstrate the utility of RNAseq in identifying causative variants in muscle diseases. Evaluation of four aberrant splicing tools allowed efficient identification of most pathogenic splicing events, obtaining a manageable number of candidate events for manual inspection, demonstrating feasibility for translation into a clinical setting. We also show how the integration of omic technologies reduces the turnaround time to identify causative variants.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141052","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":"Brain Characteristics in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder by 7.0 Tesla MRI.","authors":"Lei Su, Joseph Kuchling, Chenyang Gao, Thoralf Niendorf, Carsten Finke, Zhe Zhang, Ai Guo, Jing Jing, De-Cai Tian, Yu-Jing Li, Mengting Zhang, Xiaoyu Shi, Xinyao Liu, Huabing Wang, Yaou Liu, Claudia Chien, Michael Levy, Yunyun Duan, Friedemann Paul, Fu-Dong Shi","doi":"10.1002/acn3.70080","DOIUrl":"https://doi.org/10.1002/acn3.70080","url":null,"abstract":"<p><strong>Background: </strong>Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can radiographically mimic multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The disease hallmarks cortical lesion, central vein sign (CVS) and paramagnetic rim lesions identified in MS have not yet been comprehensively investigated in MOGAD.</p><p><strong>Methods: </strong>We have characterized 45 patients with MOGAD using 7.0 Tesla (7 T) MRI at two academic research hospitals in China and Germany. 7 T MRI, laboratory, and clinical data were collected. The classification of cortical lesions, proportion of CVS, and the phase shifts of lesions on susceptibility weighted imaging were analyzed.</p><p><strong>Results: </strong>Of the 45 patients enrolled with MOGAD, 282 lesions were identified. We further detected 31 (11%) cortical lesions including leukocortical, intracortical, and subpial types, of which intracortical lesions (16/31, 52%) were frequently involved. CVS was identified in 53 (19%) lesions of 21 (47%) patients, 154 (55%) lesions showed multiple veins sign (MVS) in 30 (67%) patients. The number (4.3 ± 6.0 vs. 1.5 ± 2.1, p = 0.0049) and percentage (52% vs. 18%, p < 0.0001) of MVS lesions for each MOGAD patient were higher than those of CVS. Eight patients (18%) had 39 (14%) lesions of hypointense signal with paramagnetic phase shifts on SWI, showing nodular phase changes and irregular borders in appearance.</p><p><strong>Conclusions: </strong>In our observational MOGAD cohort, all three types of cortical lesions were recognized, with intracortical lesions being the most common. The number and proportion of lesions with MVS were higher than those with CVS. Lesions with paramagnetic phase changes were rare and non-rim-like in appearance. These findings provide a better understanding of the underlying pathology of MOGAD and will help in the differentiation of MOGAD from other demyelinating disorders.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126317","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":"Serotonergic and Dopaminergic Function in Neuropsychiatrically Asymptomatic People With HIV on Antiretroviral Therapy.","authors":"Chuen-Yen Lau, Anna Lyndaker, Swati Shah, Paul Wakim, Amelia Mitchell, Cynthia Monroe, Alan Kim, Tracy L Cropper, Govind Nair, Joseph Snow, Bryan R Smith, Avindra Nath, Dima A Hammoud","doi":"10.1002/acn3.70074","DOIUrl":"https://doi.org/10.1002/acn3.70074","url":null,"abstract":"<p><strong>Objective: </strong>People with HIV (PWH) on antiretroviral therapy (ART) still experience neurocognitive dysfunction and accelerated brain volume loss. To assess whether the serotonergic and dopaminergic systems are affected, we used [¹¹C]DASB positron emission tomography (PET) to assess presynaptic serotonergic function and [¹⁸F]FDOPA PET to measure presynaptic dopaminergic reserve in neurocognitively and psychiatrically asymptomatic PWH on ART, compared to seronegative controls (SCs).</p><p><strong>Methods: </strong>We compared [¹¹C]DASB binding (BP_ND) (n = 17 PWH/19 SCs) and [¹⁸F]FDOPA influx constant (K_i) (n = 20 PWH/19 SCs) of PWH and SCs. We assessed correlations of K_i and BP_ND with CSF cytokines and imaging/clinical/neuropsychological outcomes using multivariable and univariable models.</p><p><strong>Results: </strong>BP_ND, K_i, and neurocognitive and psychiatric scores did not differ between PWH and SCs. Higher BP_ND correlated with better neurocognitive scores in the whole group. K_i did not correlate with neurocognitive scores. Neither BP_ND nor K_i correlated with depression scores. Caudate and putamen MRI volumes trended smaller in PWH. While CSF inflammatory cytokines were higher in PWH, they did not correlate with either PET measure.</p><p><strong>Interpretations: </strong>Presynaptic serotonin transporter density (measured by [¹¹C]DASB) is a good correlate of the neurocognitive function in PWH and SCs. Despite long-term ART, PWH still showed trends for basal ganglia volume loss, consistent with known disproportionate global and regional volume loss in PWH compared to SCs. Aspects of serotonergic and dopaminergic function, namely, presynaptic SERT density and dopaminergic reserve, however, are not different in this PWH cohort on ART from SCs, despite persistent neuroinflammation and trends of volume loss. This could reflect a functional compensatory process versus minimal, below-detection-level dysfunction.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118316","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":"Pathway Analyses of Inherited Neuropathies Identify Putative Common Mechanisms of Axon Degeneration.","authors":"Christopher R Cashman, Craig Blackstone, Reza Sadjadi","doi":"10.1002/acn3.70083","DOIUrl":"https://doi.org/10.1002/acn3.70083","url":null,"abstract":"<p><strong>Objective: </strong>Inherited neuropathies (IN) are associated with over 100 different genetic mutations presenting with a variety of phenotypes. This complexity suggests multiple pathways may converge onto a limited number of downstream pathways to effect axonal injury. Ontologic and protein-protein interaction (PPI) studies of the genes associated with inherited disorders of axon degeneration can identify these putative pathophysiologic mechanisms. Comparison with pathways in central disorders of axon degeneration may reveal universal pathways and, thus, therapeutic targets.</p><p><strong>Methods: </strong>Pathway analyses of genes associated with IN with axonal, demyelinating, and intermediate phenotypes and hereditary spastic paraplegia (HSP) were performed using the Metascape resource. The resulting PPI and ontology networks were analyzed for common and shared versus disparate pathways. Pathways from IN were also compared to those of HSP.</p><p><strong>Results: </strong>PPI networks demonstrated robust integration of the phenotype-specific networks, with over 20 hubs identified and highly interconnected networks of tRNA aminoacylation and intracellular trafficking. The voltage-gated sodium channel-associated axonal IN did not integrate with the rest of the network, prefiguring potentially different pathophysiologic processes. Ontologic analyses identified tRNA metabolism, axonal transport, and endomembrane/organelle trafficking to be common to all IN phenotypes. There was overlap of these IN ontologic processes with those identified in HSP, suggestive of common pathways involved in the development of inherited, length-dependent axonopathies.</p><p><strong>Interpretation: </strong>Intracellular trafficking and endomembrane/organelle transport are common pathways associated with inherited axonopathies. Therapies targeting tRNA metabolism and intracellular trafficking are promising therapeutic targets given the convergent PPIs of these subnetworks.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118315","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":"An Analysis for IDH-Mutant Grade 4 Astrocytoma Based on WHO CNS 5: Implication of Clinical Practice.","authors":"Xianxin Qiu, Liping Liang, Lingchao Chen, Pengjie Hong, Wanzun Lin, Jiabing Liu, Zhirui Zhou, Wenjia Zhu, Tianqi Wu, Mingyuan Pan, Yihua Zhong, Jing Gao, Zhiyong Qin, Yang Wang","doi":"10.1002/acn3.70081","DOIUrl":"https://doi.org/10.1002/acn3.70081","url":null,"abstract":"<p><strong>Purpose: </strong>There is ongoing debate regarding the therapeutic approach and prognosis for IDH-mutant grade 4 astrocytoma, a newly defined subtype of diffuse glioma in the 2021 WHO classification system for central nervous system tumors (WHO CNS 5). The aim of this study was to explore the clinical outcome and prognosticators for newly diagnosed IDH-mutant grade 4 astrocytoma based on our single institutional data.</p><p><strong>Methods: </strong>This retrospective analysis included 53 consecutive patients with newly diagnosed IDH-mutant grade 4 astrocytoma, who underwent radiotherapy between September 2021 and December 2023. All patients were administered concurrent and adjuvant temozolomide. Eleven patients received adjuvant tumor-treating fields (TTFields).</p><p><strong>Results: </strong>The median follow-up was 15.7 months. Twenty patients had tumor relapse; three patients died, all of whom were without TTFields therapy. The median PFS for the entire cohort was 19.3 months, and the median OS was not reached. Univariate analysis indicated patients younger than 40 years (p = 0.11) or without homozygous deletion of CDKN2A/B (p = 0.11) tended to have better PFS. In addition, the TTFields group tended to have longer median PFS than the non-TTFields group in both analyses before and after propensity score matching (PSM) (24.4 vs. 18.5 months, p = 0.097, before PSM; 24.4 vs. 15.9 months, p = 0.080, after PSM). No significant independent prognostic factor was found in the multivariate analysis.</p><p><strong>Conclusions: </strong>The study reveals important insights into clinical practice for IDH-mutant grade 4 astrocytoma. Younger age and tumor without deleted CDKN2A/B might be predictive of better outcomes. The addition of TTFields trended towards improved PFS, necessitating prospective clinical trials for further investigation.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118314","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}