Annals of Clinical and Translational Neurology最新文献

{"title":"Generalized Dystonia With Cervical Predominance in a Patient With a De Novo TCF20 Variant.","authors":"Melisa Kilic, Petr Dusek, Ibrahim Kamaci, Bahar Gulmez, Gul Yalcin Cakmakli, Ersin Tan, Sibel Ugur Iseri, Zuhal Yapici","doi":"10.1002/acn3.70534","DOIUrl":"10.1002/acn3.70534","url":null,"abstract":"<p><p>TCF20 has been implicated in developmental delay and intellectual disability, with dystonia reported less frequently. We describe a woman in her early twenties with childhood-onset learning difficulties, progressive dysarthria, tremor, and generalized dystonia with marked cervical predominance, associated with a de novo TCF20 frameshift variant identified by whole genome sequencing. Quantitative brain MRI demonstrated numerically increased globus pallidus susceptibility and reduced volume compared with controls, without clear evidence of iron accumulation. This case further supports generalized dystonia as a recognizable manifestation of TCF20-related disorders and suggests a possible link between TCF20 dysfunction and globus pallidus involvement in dystonia pathophysiology.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147290","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":"Subjective Cognitive Concerns and Cognitive Trajectories in Parkinson's Disease: Biomarker Impact.","authors":"Francesca V Lopez, Fareshte Erani, Katherine J Bangen, David G Coughlin, Douglas Galasko, Kelsey R Thomas","doi":"10.1002/acn3.70531","DOIUrl":"10.1002/acn3.70531","url":null,"abstract":"<p><strong>Objective: </strong>To examine the relationship of subjective cognitive concerns (SCC) with biomarkers of Alzheimer's disease (AD), neurodegeneration, and Parkinson's disease (PD) and domain-specific cognitive trajectories among cognitively unimpaired persons with de novo PD.</p><p><strong>Method: </strong>Cognitively unimpaired participants with SCC (n = 294) and without SCC (n = 857) from the Parkinson's Progression Markers Initiative underwent neuropsychological testing, lumbar puncture, and dopamine transporter (DaT) single-photon emission computed tomography (SPECT). Multiple regression analyses examined SCC associations with biomarkers of AD (CSF phosphorylated-tau181/amyloid-beta42 [p-tau181/Aβ42]), neurodegeneration (CSF neurofilament light [NfL]), and PD (DaT-SPECT in contralateral putamen). Linear mixed effects models examined 5-year cognitive trajectories (working memory, category fluency, learning and memory, visuospatial functioning, processing speed) by SCC status and the extent to which biomarkers of AD, neurodegeneration, and PD moderated these associations.</p><p><strong>Result: </strong>At baseline, the SCC group had higher p-tau181/Aβ42 (FDR-adjusted p = 0.004) than the No SCC group, while NfL and DaT-SPECT did not differ. Relative to the No SCC group, the SCC group exhibited faster decline in learning (FDR-adjusted p = 0.016), delayed recall (FDR-adjusted p = 0.016) and working memory (FDR-adjusted p = 0.016). AD and PD-related biomarkers moderated cognitive trajectories: SCC in combination with (1) higher CSF p-tau181/Aβ42 was related to steeper declines in working memory (FDR-adjusted p = 0.032); and (2) lower DaT-SPECT was related to steeper declines in delayed recall (FDR-adjusted p = 0.032).</p><p><strong>Interpretation: </strong>SCC is related to AD biomarkers and accelerated cognitive decline in the earliest stages of PD. SCC may serve as an early marker of cognitive risk, especially among persons with greater AD- or PD-related burden.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134439","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":"Anticoagulation Treatment Response Among Phenotypic ESUS Clusters: Evidence From CASPR.","authors":"Elena Badillo Goicoechea, Patrick Ellsworth, James E Siegler, James R Brorson, Christina M Lineback, Frank G Conyers, Deborah Kerrigan, Kelsey Eklund, Shadi Yaghi, Farid Khasiyev, Emiliya Melkumova, Collin J Culbertson, Marissa D'Souza, Dinesh V Jillella, Patrick Glover, Hassan Aboul-Nour, Fadi Nahab, Mahan Shahrivari, Simona Nedelcu, David S Liebeskind, Matthew M Smith, Aaron Rothstein, Anna Bowman, Alicia Zha, Narendra Kala, Ahmad Abu Qdais, Sami Al Kasab, Mudassir Farooqui, Diana Rojas-Soto, Yasmin Aziz, Franziska Herpich, Jean-Philippe Daniel, Sean L Thompson, Vivek Patel, Thanh N Nguyen, Siddharth Sehgal, Wenzheng Yu, Wayneho Kam, Russel Van Coevering, Oana M Dumitrascu, Muhammad Alvi, Balaji Krishnaiah, Setareh Salehi Omran, Guillermo Linares, Eesha Singh, Hamid Ali, Mary Penckofer, Jesse M Thon, Shani Mannion, Dalia Chahien, Lucia Chen, Fawad Talat, Mehdi Abbasi, Richa Sharma","doi":"10.1002/acn3.70542","DOIUrl":"10.1002/acn3.70542","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate treatment effect heterogeneity across phenotypic clusters of patients with cryptogenic embolic stroke using causal inference methods.</p><p><strong>Methods: </strong>From a retrospective, multicenter cohort of patients with cryptogenic embolic stroke, we estimated the treatment effect of anticoagulation versus antiplatelet therapy in patients with ESUS in two ways: (1) Partitioning Around Medoids and (2) causal survival forest modeling. We assessed cluster-level associations with time to primary outcome (recurrent stroke, major bleeding, or death) using Kaplan-Meier survival analysis to assess cluster differences. We then extracted SHapley Additive exPlanations (SHAP) feature importances from the causal forest model to identify candidate effect modifiers from the causal forest.</p><p><strong>Results: </strong>Among 1869 patients with ESUS, three phenotypically distinct clusters were extracted with significant differences in event-free survival across clusters (log-rank p < 0.0001). There was no significant population-level benefit of anticoagulation over antiplatelet therapy (p = 0.23). SHAP feature importance analysis identified several candidate effect modifiers; however, only higher LVEF (β = -327, 95% CI: -580 to -74, p = 0.011) and cancer history (β = -226, 95% CI: -441 to -11, p = 0.039) were independent predictors of response to antiplatelet over anticoagulation using best linear projections. Phenotypic cluster assignment did not significantly predict treatment effect heterogeneity.</p><p><strong>Interpretation: </strong>Three distinct phenotypic clusters of cryptogenic stroke patients emerged with a differential risk of the composite outcome, but they did not predict responsiveness to anticoagulation. LVEF and cancer history, however, showed differential outcomes across antithrombotic strategies. These findings demonstrate the potential of causal inference methods for identifying effect heterogeneity and individualizing treatment strategies.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101682","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":"Advancing Stroke Clinical Trials Using Community Engagement and Implementation Science Approaches","authors":"Lesli E. Skolarus,&nbsp;Devin L. Brown,&nbsp;Bernadette Boden-Albala","doi":"10.1002/acn3.70461","DOIUrl":"10.1002/acn3.70461","url":null,"abstract":"<p>Stroke clinical trials are essential for advancing stroke care but can face challenges with recruitment, retention, clinical relevance, and translation into real-world practice. We propose that integrating community engagement and implementation science approaches into stroke trials can help address these needs. We conceptualize clinical trials as an evidence-based practice and highlight that implementation frameworks linked to implementation strategies can be used to anticipate and address multilevel trial determinants. We also describe how engaging constituents across the trial lifecycle can support negotiation of inevitable trade-offs and alignment of trial decisions with the needs, capacities, and priorities of those affected, including those responsible for implementing findings. We propose that integrating community engagement and implementation science has the potential to improve trial efficiency, strengthen relevance, accelerate translation into real-world practice, and advance stroke health for all.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2148-2153"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325116","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":"Advancing Age Modulates Associations Between Cognitive Impairment and Brain Volumes in Early MS","authors":"Piriyankan Ananthavarathan,&nbsp;Marco Pitteri,&nbsp;Michael Foster,&nbsp;Sara Collorone,&nbsp;Sara Salama,&nbsp;Elisa Colato,&nbsp;Ferran Prados,&nbsp;Baris Kanber,&nbsp;Marios Yiannakas,&nbsp;Claudia A. M. Gandini Wheeler-Kingshott,&nbsp;Indran Davagnanam,&nbsp;Frederik Barkhof,&nbsp;Declan Chard,&nbsp;Olga Ciccarelli,&nbsp;Ahmed Toosy","doi":"10.1002/acn3.70385","DOIUrl":"10.1002/acn3.70385","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Cognitive impairment is common in multiple sclerosis (MS), but manifestations following the first demyelinating event are relatively unexplored. We investigated cross-sectional associations between magnetic resonance imaging (MRI)–derived brain volumes and the presence of cognitive impairment outcomes five years after the first presentation with a demyelinating event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Comprehensive cognitive assessments were performed five years after a first clinical demyelinating presentation using the Minimal Assessment of Cognitive Function in MS (MACFIMS). Participant <i>Z</i> scores were calculated for each MACFIMS subtest using available regression-based normative data. Participants were defined as having a cognitive outcome if one or more MACFIMS subtests were below the applied cutoff of <i>Z</i> ≤ −1.50. Gray matter volumes (GMV) were calculated using 3D T1-weighted MRI sequences. Logistic regression models assessed associations between 5-year MRI measures and cognitive impairment (adjusting for total intracranial volume where relevant).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty participants were recruited. Lower GMV at 5 years was associated with 5-year cognitive impairment outcomes (OR = 1.06 per 1 cm³ decrease in GMV, 95% CI [1.00–1.13], <i>p</i> = 0.044). Among participants with a cognitive impairment outcome, there were significant associations between lower GMV and advancing age (<i>p</i> = 0.0095). Exploratory analysis of estimated marginal contrasts suggested that cognitive impairment outcomes were potentially associated with GMV above the age of 39 years (<i>Z</i> ≤ −1.50: <i>p</i> = 0.0476).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Five years after a first demyelinating event, GMV volumes on MRI are significantly associated with the presence of cognitive outcomes, while advancing age also appears to be associated with GMV and cognitive outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2124-2133"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643412","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 Multiple Sclerosis Severity Allele rs10191329A and Cognitive Function: A UK Biobank Study","authors":"Ioanna Zimianiti,&nbsp;Sheena Waters,&nbsp;Adil Harroud,&nbsp;Pernilla Stridh,&nbsp;Ruth Dobson,&nbsp;Benjamin M. Jacobs","doi":"10.1002/acn3.70458","DOIUrl":"10.1002/acn3.70458","url":null,"abstract":"<p>The genome-wide association study of Multiple Sclerosis severity linked the genetic variant rs10191329^A to long-term disability and implicated brain resilience as a determinant of outcome. We hypothesised that rs10191329^A might influence cognition in other neurological diseases and healthy controls. We explored the relationship between rs10191329^A and cognition using reaction time, fluid intelligence, and prospective memory tests in the UK Biobank. We observed weak but directionally consistent associations between rs10191329^A and poorer cognition in controls, with similar but non-significant trends in Multiple Sclerosis, Parkinson's disease, and dementia. Our results support the hypothesis that rs10191329^A might affect multiple sclerosis outcomes by affecting brain health.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2143-2147"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292661","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":"Posterior Cortical Atrophy in the Asia-Pacific: A Report From the PCA Asian Workgroup","authors":"Yuttachai Likitjaroen,&nbsp;Ya-Ting Chang,&nbsp;Levinia Lim,&nbsp;Pai-Yi Chiu,&nbsp;Jung-Lung Hsu,&nbsp;SangYun Kim,&nbsp;Wataru Narita,&nbsp;Na Young Ryoo,&nbsp;Kyoko Suzuki,&nbsp;Nagaendran Kandiah,&nbsp;Sebastian Crutch,&nbsp;Ming-Chyi Pai","doi":"10.1002/acn3.70347","DOIUrl":"10.1002/acn3.70347","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Posterior Cortical Atrophy (PCA) is a distinct dementia syndrome primarily affecting spatial abilities and visual processing. It is associated with degeneration in the posterior part of the brain. PCA is subclassified into PCA-pure and PCA-plus syndromes based on consensus criteria. To address this, the PCA Asia Workgroup was established to study PCA in Asian countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Asia PCA Workgroup collected demographic and clinical data, including symptoms and signs, from PCA patients. Patients were classified into PCA-pure (solely meeting PCA criteria) and PCA-plus (additional features of other neurodegenerative syndromes). The frequency of clinical presentations, symptoms, and signs was compared to the consensus classification estimation and the meta-analysis of published data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PCA-pure (76.2%) was the most common subtype, with earlier onset (80.95%) and distinct early prominent deficit of executive/memory &gt; visual disturbances which is different from the consensus study has estimated and the meta-analysis of published data. PCA-Lewy body disease (PCA-DLB) exhibited higher frequencies of attention deficits, visual hallucinations, cognitive fluctuations, and rigidity compared to PCA-pure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study reveals the real-world clinical presentation of PCA syndrome in an Asian population, emphasizing the differences from consensus estimations and the meta-analysis of published data. Further research is needed to validate these findings and compare them with real clinical data from PCA patients of other ethnicities, in order to gain a comprehensive understanding of PCA worldwide.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"1993-2001"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508235","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":"Multiple Sclerosis Relapse Activity After Ozanimod Discontinuation in DAYBREAK Trial Participants","authors":"Ralf Gold,&nbsp;Krzysztof W. Selmaj,&nbsp;Regina Berkovich,&nbsp;Jeffrey A. Cohen,&nbsp;Giancarlo Comi,&nbsp;Eva K. Havrdová,&nbsp;James K. Sheffield,&nbsp;Hetal Desai,&nbsp;Chun-Yen Cheng,&nbsp;Jon V. Riolo,&nbsp;Andrew Thorpe,&nbsp;Erik DeBoer,&nbsp;Bruce A. C. Cree","doi":"10.1002/acn3.70366","DOIUrl":"10.1002/acn3.70366","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Return of disease activity is expected when patients discontinue disease-modifying therapy (DMT) for multiple sclerosis (MS). Some MS DMTs are associated with higher-than-expected disease activity (rebound) after discontinuation. This exploratory analysis assessed disease activity and risk of rebound after ozanimod discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DAYBREAK (NCT02576717; October 2015–April 2023) was a single-arm, open-label extension trial of ozanimod 0.92 mg/d in participants with relapsing MS who completed phase 1–3 ozanimod trials. Two protocol amendments increased the required safety follow-up from an initial 28 days to 75 and then 90 days. Confirmed post-treatment relapses were characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 2494 participants, 1679 participants had ≥ 1 day of follow-up and did not initiate commercial ozanimod in ≤ 14 days of exiting the trial; 30.6% had ≤ 60 days of post-treatment follow-up. Fifty-five participants (3.3%) had known post-treatment relapse. Fifty-four were not taking an MS DMT when they relapsed; one relapsed soon after starting fingolimod. Relapses were associated with Expanded Disability Status Scale (EDSS) score increases of 0–3 points (median 1 point); the participant with the 3-point increase had a moderate relapse and complete recovery in 23 days. Forty-two participants (76.4%) fully recovered, 11 (20.0%) partially recovered, and 2 (3.6%) did not recover. Only one (1.8%) relapse was considered severe by the investigator: EDSS increased from 7.5 to 8.0, and the participant partially recovered within 36 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Most participants did not relapse within 90 days following ozanimod discontinuation. Post-treatment relapse cases suggestive of a rebound effect were not observed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2017-2026"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519426","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":"Choroid Plexus Enlargement and USPIO-Based Inflammatory Feature in Cerebral Small Vessel Disease","authors":"Yongqiang Qu,&nbsp;Xiaoning Ren,&nbsp;Cuihua Fan,&nbsp;Chun Li,&nbsp;Lijie Zhang,&nbsp;Zaiqiang Zhang,&nbsp;Shaowu Li,&nbsp;Zhongmeng Lai,&nbsp;Bin Cai,&nbsp;Ying Fu,&nbsp;Yi Lin,&nbsp;Zhibao Zhu","doi":"10.1002/acn3.70382","DOIUrl":"10.1002/acn3.70382","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The choroid plexus (CP) is a key component of the blood–cerebrospinal fluid barrier (BCSFB), but its mechanism of action in cerebral small vessel disease (CSVD) remains unclear. This study investigated CP volume (CPV) alterations and their association with conventional imaging markers in CSVD and explored the underlying role of inflammation using ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, 111 CSVD patients and 69 healthy controls (HC) underwent 3.0 T conventional MRI to quantify CPV in the lateral (LV), third (3 V), and fourth (4 V) ventricles. CSVD burden was evaluated using visual assessment scales, including indicators such as white matter hyperintensities (WMH), lacunes, basal ganglia-enlarged perivascular spaces (BG-EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA). A subgroup (22 CSVD, 10 HC) underwent USPIO-enhanced MRI to measure the change of signal intensity ratio (∆SIR) as a feature of inflammatory activity in the CP and deep gray matter nuclei.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CSVD patients showed significantly larger CPV (all <i>p</i> &lt; 0.001). CPV demonstrated significant positive correlations with the severity of conventional CSVD imaging markers (all <i>p</i> &lt; 0.05). USPIO-enhanced MRI revealed an increased ΔSIR in the LV, 3 V, and 4 V CP (all <i>p</i> &lt; 0.05). Furthermore, increased USPIO uptake was observed in deep gray matter nuclei in CSVD. Crucially, a positive correlation was found between LV CP volume and ΔSIR (<i>r</i> = 0.375, <i>p</i> = 0.034), and the LV CP inflammation was strongly correlated with the hippocampus (<i>r</i> = 0.582, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>CP enlargement is prominent in CSVD and closely linked to the CSVD imaging burden. CP inflammation is associated with increased volume. CP may be a novel biomarker to help diagnose, monitor, and treat neuroinflammation in CSVD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2078-2087"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621314","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":"Prognostic Value of Neurofilament Light Chain and Glial Fibrillary Acidic Protein in ALD-Related Myelopathy","authors":"Eda G. Kabak,&nbsp;Marije M. C. Voermans,&nbsp;Hans Heijst,&nbsp;Charlotte E. Teunissen,&nbsp;Marc Engelen","doi":"10.1002/acn3.70386","DOIUrl":"10.1002/acn3.70386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>X-linked adrenoleukodystrophy (X-ALD) is a neurometabolic disorder caused by pathogenic variants in <i>ABCD1</i>, leading to slowly progressive spinal cord disease in nearly all affected men. Sensitive biomarkers to quantify disease severity and predict progression are needed for clinical care and trial design. Plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are promising biomarkers reflecting axonal and astroglial injury. This study evaluated their prognostic value for spinal cord disease progression in X-ALD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a prospective, seven-year longitudinal study, 66 adult male X-ALD patients without cerebral involvement were followed. Plasma NfL and GFAP were measured using single-molecule array (Simoa) technology. Patients were stratified by baseline biomarker levels using cohort-based fourth-quartile cut-offs (NfL &lt; 15.7 vs. ≥ 15.7 pg/mL; GFAP &lt; 78.7 vs. ≥ 78.7 pg/mL). Age-adjusted NfL residuals were calculated from baseline log-transformed NfL regressed on age. Longitudinal trajectories of the EDSS, SSPROM, and 6-MWT were analyzed using linear mixed-effect models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High baseline NfL was associated with faster EDSS progression (<i>p</i> &lt; 0.001) and steeper SSPROM decline, with differences emerging within the first year. Overall plasma NfL levels remained stable over time (<i>p</i> = 0.111). Age-adjusted NfL residuals showed significant slope differences between the mean and high (+1 SD) and very high (+2 SD) groups. GFAP stratification showed limited prognostic value, with only a significant decline in both groups for SSPROM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Baseline plasma NfL is a robust prognostic biomarker for spinal cord disease progression in adult X-ALD and supports its use for patient stratification in clinical trials, whereas GFAP shows limited standalone utility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2114-2123"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147631952","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}